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Cell Transplantation : The Regenerative Medicine Journal

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Volume 26, Number 6 Reviews Pig-to-Primate Islet Xenotransplantation: Past, Present, and Future 925Zhengzhao Liu,Wenbao Hu, Tian He,Yifan Dai, Hidetaka Hara, RitaBottino, David K. C. Cooper,Zhiming Cai, andLisha Mou

Using Electrical Stimulation to Enhance the Efficacy of Cell Transplantation Therapies for Neurodegenerative Retinal Diseases: Concepts, Challenges, and Future Perspectives 949Abby LeighManthey, Wei Liu,Zhi Xin Jiang, MarcusHiu Kong Lee, Jian Ji, Kwok-Fai So, JimmyShiu Ming Lai, Vincent Wing Hong Lee, and Kin Chiu

Original Contributions

OlfactoryEnsheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Mller Cell Notch Signaling Pathway 967JingXie,Shujia Huo,Yijian Li,Jiaman Dai,Haiwei Xu, and Zheng Qin Yin

EarlySubretinal Allograft Rejection Is Characterized by Innate Immune Activity 983Kevin P. Kennelly, Toby M. Holmes, Deborah M. Wallace, ClionaOFarrelly, and David J. Keegan

Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury 1001Miyeoun Song, Jae-Hyung Lee,Jinhyun Bae,Youngmin Bu, andEun-Cheol Kim

The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental RenalAllotransplantation 1017Ana Merino, Elia Ripoll, Laura de Ramon,Nuria Bolaos, Montserrat Goma, OriolBestard,Nuria Lloberas,Josep M.Grinyo, and JuanTorras Ambrs

Human Umbilical Cord Mesenchymal Stem Cells Inhibit T Follicular Helper Cell Expansion Through the Activation ofiNOS in Lupus-Prone B6.MRL-Faslpr Mice 1031Zhuoya Zhang,Ruihai Feng,Lingying Niu,Saisai Huang, Wei Deng,Bingyu Shi,Genhong Yao,Weiwei Chen,Xiaojun Tang, Xiang Gao,Xuebing Feng, andLingyun Sun

CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells 1043Yoshikazu Matsuoka, Masaya Takahashi, KeisukeSumide, Hiroshi Kawamura,Ryusuke Nakatsuka, Tatsuya Fujioka, and YoshiakiSonoda

Long-Term Follow-Up of Patients After Autologous Bone Marrow Cell Infusion for Decompensated Liver Cirrhosis 1059Ja Kyung Kim, Soo-Jeong Kim, Yuri Kim, YongEun Chung, YoungNyun Park, Hyun Ok Kim,Jin Seok Kim,Mi-Suk Park, IsaoSakaida, Do Young Kim, Jung Il Lee, SangHoon Ahn, KwanSik Lee, and Kwang-HyubHan

Calcium Concentration in Culture Medium as a Nondestructive and Rapid Marker of Osteogenesis 1067Yohei Tanikake, ManabuAkahane, Akira Furukawa,Yasuaki Tohma, Yusuke Inagaki, Tsutomu Kira, andYasuhito Tanaka

Cisplatin-ImpairedAdipogenic Differentiation of Adipose Mesenchymal Stem Cells 1077Yu-Hsun Chang, Hwan-Wun Liu, Tang-Yuan Chu, Yao-Tseng Wen,Rong-Kung Tsai, and Dah-Ching Ding

Effects of Different Cell-Detaching Methods on the Viability and Cell Surface Antigen Expression of Synovial Mesenchymal Stem Cells 1089Kunikazu Tsuji,Miyoko Ojima, KojiOtabe,Masafumi Horie, Hideyuki Koga, Ichiro Sekiya, and TakeshiMuneta

Human Muscle Precursor Cells Overexpressing PGC-1a Enhance Early Skeletal Muscle Tissue Formation 1103DeanaHaralampieva, SouzanSalemi, IvanaDinulovic,Tullio Sulser, Simon M.Ametamey, ChristophHandschin, and DanielEberli

Volume 26, Number 5

GeoffreyRaisman, 19392017: Opening a Scientific Door and Giving Hope 733 Paul R.Sanberg

Review

Conceptual Design and Procedure for an AutonomousIntramyocardial Injection Catheter 735 Weyland Cheng and Peter K. Law

Original Contributions

Hydrogen Sulfide Reduces Recruitment of CD11b+Gr-1+Cells in Mice With Myocardial Infarction 753 Ting Wu, Hua Li, Bing Wu, Lei Zhang, San-wu Wu,Jia-ning Wang, and You-en Zhang

Developing a Rapid Algorithm to Enable Rapid Characterization of Alginate Microcapsules 765 Ka Hei Chan, Rahul Krishnan, Michael Alexander, and Jonathan R. T.Lakey

StemCell Keep Is Effective for Cryopreservation of Human Embryonic Stem Cells byVitrification 773 Akemi Ota, Kazuaki Matsumura, Jun-Jae Lee,Shoichiro Sumi, andSoung-Hyu Hyon

In VitroMicrovibration Increases Implantation Rate After Embryonic Cell Transplantation 789 VladimirIsachenko, KarlSterzik, RobertMaettner,Evgenia Isachenko,Plamen Todorov,Gohar Rahimi, PeterMallmann, ErwinStrehler, IgorPereligin, Jos LuisAlabart, and MarkusMerzenich

Changes in Sexual Behavior ofOrchidectomized Rats Under Influence ofAllotransplantation of Testicular Interstitial Cell Suspension 795 Bo Deng, TatyanaBondarenko, andOleksandr Pakhomov

Precise Regulation of miR-210 Is Critical for the Cellular Homeostasis Maintenance and Transplantation Efficacy Enhancement of Mesenchymal Stem Cells in Acute Liver Failure Therapy 805 Yingxia Liu,Yongjia Xiong,Feiyue Xing,Hao Gao,Xiaogang Wang,Liumin He,Chaoran Ren, Lei Liu, Kwok-Fai So, andJia Xiao

Human Muse Cells,Nontumorigenic Pluripotent-Like Stem Cells, Have Liver Regeneration Capacity Through Specific Homing and Cell Replacement in a Mouse Model of Liver Fibrosis 821 Masahiro Iseki, YoshihiroKushida,Shohei Wakao, Takahiro Akimoto,Masamichi Mizuma,Fuyuhiko Motoi,Ryuta Asada,Shinobu Shimizu, MichiakiUnno, GregorioChazenbalk, and MariDezawa

Phenotypical and Functional Characteristics of In Vitro-Expanded Adipose-Derived Mesenchymal Stromal Cells From Patients With Systematic Sclerosis 841 ChiaraCapelli, EleonoraZaccara, Paola Cipriani, Paola Di Benedetto, WandaMaglione, RominaAndracco, Gabriele Di Luca, FrancescaPignataro, RobertoGiacomelli, MartinoIntrona,ClaudioVitali, and Nicoletta Del Papa

Are Adipose-Derived Stem Cells From LiverFalciform Ligaments Another Possible Source of Mesenchymal Stem Cells? 855 Sang Woo Lee, JaeUk Chong,Seon Ok Min,Seon YoungBak, and KyungSik Kim

Effect of Bone Marrow Aspirate ConcentratePlatelet-Rich Plasma on Tendon-Derived Stem Cells and Rotator Cuff Tendon Tear 867 SunJeong Kim, Da Hyun Song, JongWook Park, Silvia Park, and Sang Jun Kim

Human Bone Progenitor Cells for Clinical Application: What Kind of Immune Reaction Does Fetal Xenograft Tissue Trigger in Immunocompetent Rats? 879 Tanja C.Hausherr,Katja Nuss, Eric Thein, Lee A. Applegate, and Dominique P.Pioletti

Clinical Study ofNeuroRegen Scaffold Combined With Human Mesenchymal Stem Cells for the Repair of Chronic Complete Spinal Cord Injury 891 Yannan Zhao,Fengwu Tang,Zhifeng Xiao,Guang Han,NuoWang, Na Yin, Bing Chen,Xianfeng Jiang, Chen Yun,Wanjun Han, Changyu Zhao,Shixiang Cheng, Sai Zhang, andJianwu Dai

Transgenic Expression of Glucagon-Like Peptide-1 (GLP-1) and Activated Muscarinic Receptor (M3R) Significantly Improves Pig Islet Secretory Function 901 Nizar I.Mourad, AndreaPerota,Daela Xhema, Cesare Galli, and PierreGianello

Transplantation of Cultured Olfactory Bulb Cells Prevents Abnormal Sensory Responses During Recovery From Dorsal Root Avulsion in the Rat 913 Andrew Collins, Daqing Li, Stephen B. McMahon, GeoffreyRaisman, and Ying Li

SPECIAL ISSUE 24th MEETING OF THE AMERICAN SOCIETY FOR NEURAL THERAPY AND REPAIR (ASNTR)Recent Progress in Cell Therapy and Regenerative Medicine for Neurological Disorders: Introduction to the ASNTR Special Issue From the 2016 Meeting 529 Cesar V.Borlongan

Is Immune Modulation the Mechanism Underlying the Beneficial Effects of Amniotic Cells and Their Derivatives in Regenerative Medicine? 531 Antonietta R.Silini, MartaMagatti, AnnaCargnoni, and OrnellaParolini

Human Amnion Epithelial Cells Protect Against White Matter Brain Injury After Repeated Endotoxin Exposure in the Preterm Ovine Fetus 541 TamaraYawno,Tharani Sabaretnam,Jingang Li, Courtney McDonald, Rebecca Lim, Graham Jenkin, Euan M. Wallace, and Suzanne L. Miller

Repetitive and Prolonged Omega-3 Fatty Acid Treatment After Traumatic Brain Injury Enhances Long-Term Tissue Restoration and Cognitive Recovery 555 Hongjian Pu,Xiaoyan Jiang,Zhishuo Wei,Dandan Hong,Sulaiman Hassan,Wenting Zhang,Jialin Liu,Hengxing Meng,Yejie Shi, Ling Chen, and Jun Chen

A Novel CXCR4 Antagonist CX549 Induces Neuroprotection in Stroke Brain 571 Kuo-Jen Wu,Seong-Jin Yu,Kak-Shan Shia,Chien-Huang Wu, Jen-Shin Song,Hsuan-HaoKuan, Kai-ChiaYeh,Chiung-Tong Chen,Eunkyune Bae, and Yun Wang

A Comparative Study of Three Different Types of Stem Cells for Treatment of Rat Spinal Cord Injury 585 JiriRuzicka, LuciaMachova-Urdzikova, JohnGillick, TakashiAmemori,Nataliya Romanyuk,Kristyna Karova,Kristyna Zaviskova, JanaDubisova,Sarka Kubinova, RajMurali, EvaSykova,Meena Jhanwar-Uniyal, andPavla Jendelova

Fate of Neural Progenitor Cells Transplanted Into Jaundiced andNonjaundiced Rat Brains 605 Fu-Chen Yang, Sean M. Riordan, Michelle Winter, Li Gan, Peter G. Smith, Jay L. Vivian, Steven M. Shapiro, and John A. Stanford

Real-Time Intraoperative MRI Intracerebral Delivery of Induced Pluripotent Stem Cell-Derived Neurons 613 Scott C.Vermilyea,Jianfeng Lu, Miles Olsen, Scott Guthrie,Yunlong Tao, Eva M.Fekete, Marissa K. Riedel, Kevin Brunner, Carissa Boettcher,Viktorya Bondarenko, Ethan Brodsky, Walter F. Block, Andrew Alexander, Su-Chun Zhang, and Marina E.Emborg

A Comparison of Exogenous Labels for the Histological Identification of Transplanted Neural Stem Cells 625 Francesca J. Nicholls, Jessie R. Liu, and MichelModo

Transplantation of Mesenchymal Stromal Cells in Patients With Amyotrophic Lateral Sclerosis: Results of Phase I/IIa Clinical Trial 647 EvaSykov, PetrRychmach, IvanaDrahordov,imona Konrdov,Kateina Rikov, IvanVoek,Serhiy Forostyak,Ale Homola, and MartinBojar

Step Sequence Is a Critical Gait Parameter of Unilateral 6-OHDA Parkinsons Rat Models 659 Heather A. Baldwin,Pyry P.Koivula, Julie C.Necarsulmer, Keith W. Whitaker, and Brandon K. Harvey

Brilliant Blue G, But Not Fenofibrate, Treatment RevertsHemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinsons Disease 669 Enas G.Ferrazoli,Hllio D.N. de Souza, Isis C.Nascimento,gatha Oliveira-Giacomelli,Telma T.Schwindt, Luiz R.Britto, and Henning Ulrich

A Subpopulation of Dopaminergic NeuronsCoexpresses Serotonin in Ventral Mesencephalic Cultures But Not AfterIntrastriatal Transplantation in a Rat Model of Parkinsons Disease 679 Stefano Di Santo, Stefanie Seiler,Anglique D.Ducray, Morten Meyer, and Hans RudolfWidmer

Regulator of Cell Cycle (RGCC) Expression During the Progression of Alzheimers Disease 693 Scott E. Counts and Elliott J.Mufson

Abstracts for the 24th Annual Meeting of the American Society for Neural Therapy and Repair 703

Volume 26, Number 3

Precision Therapy: Cell Therapy and Development of New Drugs 379 ShinnZong Lin

The Regulatory Effects of Transforming Growth Factor- on Nerve Regeneration 381 Shiying Li,Xiaosong Gu, and Sheng Yi

GSK-3 Inhibition Induced Neuroprotection, Regeneration, and Functional Recovery After Intracerebral Hemorrhagic Stroke 395 Yingying Zhao, ZhengZachory Wei, JamesYa Zhang,Yongbo Zhang,Soonmi Won,Jinmei Sun, Shan Ping Yu,Jimei Li, and Ling Wei

Neuroprotection of Granulocyte Colony-Stimulating Factor for Early Stage Parkinsons Disease 409 Sheng-Tzung Tsai, Sung-Chao Chu, Shu-Hsin Liu, Cheng-Yoong Pang, Ting-WenHou, Shinn-Zong Lin, and Shin-Yuan Chen

Chondrogenic Differentiation of Mesenchymal Stem Cells in Three-Dimensional Chitosan Film Culture 417 Tsai-Jung Lu, Fang-Yao Chiu, Hsiao-Ying Chiu, Ming-Chau Chang, and Shih-Chieh Hung

Pre-S2 Mutant-Induced Mammalian Target of Rapamycin Signal Pathways as Potential Therapeutic Targets for Hepatitis B Virus-Associated Hepatocellular Carcinoma 429 Chiao-FangTeng, Han-Chieh Wu,Woei-Cherng Shyu, Long-BinJeng, andIh-Jen Su

Mesenchymal Stem Cells: The Magic Cure for Intraventricular Hemorrhage? 439 Won Soon Park, So YoonAhn, Se In Sung,Jee-YinAhn, and Yun Sil Chang

Commercial Production of Autologous Stem Cells and Their Therapeutic Potential for Liver Cirrhosis 449 Yi-Chun Lin,Horng-Jyh Harn, Po-Cheng Lin, Ming-Hsi Chuang, Chun-Hung Chen, Shinn-Zong Lin, andTzyy-WenChiou

Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke 461 Toru Yamashita,Wentao Liu, Yoshiaki Matsumura,Ryosuke Miyagi, YunZhai,Momoko Kusaki,Nozomi Hishikawa,Yasuyuki Ohta, Sung Min Kim, Tae HwanKwak, DongWook Han, and Koji Abe

Neural Stem Cell-Conditioned Medium Suppresses Inflammation and Promotes Spinal Cord Injury Recovery 469 Zhijian Cheng, Dale B. Bosco, Li Sun,Xiaoming Chen,Yunsheng Xu,Wenjiao Tai, Ruth Didier, Jinhua Li,Jianqing Fan,Xijing He, and Yi Ren

Cell Therapy Regulation in Taiwan 483 Yuan-Chuan Chen,Hwei-Fang Cheng, and Ming-KungYeh

Adiponectin Potentially Contributes to theAntidepressive Effects ofBaduanjin Qigong Exercise in Women With Chronic Fatigue Syndrome-Like Illness 493 Jessie S. M. Chan, Ang Li, Siu-man Ng, Rainbow T. H. Ho,Aimin Xu,Tzy-jyun Yao, Xiao-Min Wang, Kwok-Fai So, and Cecilia L. W. Chan

Treatment of Spinocerebellar Ataxia With Mesenchymal Stem Cells: A Phase I/IIa Clinical Study 503 Yun-An Tsai, Ren-Shyan Liu,Jiing-FengLirng, Bang-Hung Yang, Chin-Hao Chang, Yi-Chen Wang, Yu-Shan Wu, Jennifer Hui-Chun Ho, Oscar K. Lee, and Bing-Wen Soong

Imbalanced Production of Reactive Oxygen Species and Mitochondrial Antioxidant SOD2 inFabry Disease-Specific Human Induced Pluripotent Stem Cell-Differentiated Vascular Endothelial Cells 513 Wei-Lien Tseng, Shih-Jie Chou, Huai-Chih Chiang, Mong-Lien Wang, Chian-Shiu Chien,Kuan-Hsuan Chen,Hsin-BangLeu,Chien-Ying Wang,Yuh-Lih Chang, Yung-Yang Liu,Yuh-Jyh Jong, Shinn-Zong Lin, Shih-HwaChiou,Shing-Jong Lin, and Wen-Chung Yu

Volume 26, Number 2

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors 173 Jie Xie, Thomas J. Jones,Dongni Feng, Todd G. Cook, Andrea A. Jester, Ru Yi,Yameena T. Jawed, CliffordBabbey, Keith L. March, and Michael P. Murphy

CXCR4 Overexpression in Human Adipose Tissue-Derived Stem Cells Improves Homing and Engraftment in an Animal Limb Ischemia Model 191 MiJung Kim, Dong-Ik Kim,Eun Key Kim, and Chan-Wha Kim

ALLogeneic HeartSTem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: Rationale and Design 205 Tarun Chakravarty, Raj R.Makkar, Deborah D.Ascheim, Jay H. Traverse, Richard Schatz, AnthonyDeMaria, Gary S. Francis, Thomas J.Povsic, Rachel R. Smith, Joao A. Lima, Janice M.Pogoda, LindaMarbn, and Timothy D. Henry

A Nerve Conduit Containing a Vascular Bundle and Implanted With Bone Marrow Stromal Cells and Decellularized Allogenic Nerve Matrix 215 YukitoshiKaizawa,Ryosuke Kakinoki,Ryosuke Ikeguchi,Soichi Ohta, Takashi Noguchi,Hisataka Takeuchi, Hiroki Oda, HirofumiYurie, and Shuichi Matsuda

Bone Marrow Stromal Cells Combined With SodiumFerulate andn-Butylidenephthalide Promote the Effect of Therapeutic Angiogenesis via Advancing Astrocyte-Derived Trophic Factors After Ischemic Stroke 229 Qian Zhang, Zhen-Wei Chen, Yong-Hua Zhao, Bo-Wen Liu,Nai-Wei Liu, Chien-ChihKe, and Hong-Mei Tan

Secondary Release of Exosomes From Astrocytes Contributes to the Increase in Neural Plasticity and Improvement of Functional Recovery After Stroke in Rats Treated With Exosomes Harvested From MicroRNA 133b-Overexpressing Multipotent Mesenchymal Stromal Cells 243 Hongqi Xin,Fengjie Wang,Yanfeng Li, Qing-e Lu, Wing Lee Cheung, Yi Zhang, Zheng Gang Zhang, and MichaelChopp

Efficacy of Two Delivery Routes for Transplanting Human Neural Progenitor Cells (NPCs) Into the Spastic HanWistar Rat, a Model of Ataxia 259 Toni L.Uhlendorf, Ruslan L.Nuryyev, Alex O.Kopyov, Jessica Ochoa, ShahabYounesi, Randy W. Cohen, and Oleg V.Kopyov

Establishment and Characterization of Immortalized Minipig Neural Stem Cell Line 271 Sung S. Choi,Seung-Bin Yoon, Sang-Rae Lee, Sun-Uk Kim, YoungJoo Cha, Daniel Lee,Seung U. Kim,Kyu-Tae Chang, and Hong J. Lee

Safety of Intra-Arterial Injection With Tumor-Activated T Cells to the Rabbit Brain Evaluated by MRI and SPECT/CT 283 Johan Lundberg, EmmaJussing, Zhenjiang Liu,Qingda Meng, Martin Rao, ErikSamn,Rikard Grankvist, PeterDamberg, ErnestDodoo, MarkusMaeurer, andStaffan Holmin

Significantly Accelerated Wound Healing of Full-Thickness Skin Using a Novel Composite Gel of Porcine Acellular Dermal Matrix and Human Peripheral Blood Cells 293 Vijay K. Kuna, Arvind M. Padma,Joakim Hkansson, JanNygren, RobertSjback,Sarunas Petronis, andSuchitra Sumitran-Holgersson

Human Recombinant Antithrombin (ATryn) Administration Improves Survival and Prevents Intravascular Coagulation After Intraportal Islet Transplantation in a Piglet Model 309 ValeryGmyr, Caroline Bonner, ErickaMoerman, AntoineTournoys, NathalieDelalleau, AudreyQuenon, JulienThevenet, MikaelChetboun, Julie Kerr-Conte, FranoisPattou, Thomas Hubert, andMerce Jourdain

Monocyte-Derived Dendritic Cells Impair Early Graft Function Following Allogeneic Islet Transplantation 319 Kevin V. Chow, Emma M. Carrington,Yifan Zhan, Andrew M. Lew, and Robyn M. Sutherland

Thrombospondin-1-Derived Peptide RFYVVMWK Improves the Adhesive Phenotype of CD34+ Cells From Atherosclerotic Patients With Type 2 Diabetes 327 SylvieCointe, ricRhaume, Catherine Martel, Olivier Blanc-Brude,Evemie Dub, Florence Sabatier, FranoiseDignat-George, Jean-Claude Tardif, and ArnaudBonnefoy

Fetal Tissues Tested for Microbial Sterility by Culture- and PCR-Based Methods Can be Safely Used in Clinics 339 Yakov Vitrenko,Iryna Kostenko,Kateryna Kulebyakina,Alla Duda,Mariya Klunnyk, and KhrystynaSorochynska

Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 DaysPostsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy 351 Astrid Herrero, JuliePrigent, Catherine Lombard,Valrie Rosseels, MartineDaujat-Chavanieu,Karine Breckpot, MustaphaNajimi,Gisle Deblandre, and Etienne M.Sokal

-Catenin Accumulation Is Associated With Increased Expression ofNanog Protein and Predicts Maintenance of MSC Self-Renewal 365 Sang-Jin Yu, Hyun-Je Kim,Eui Seok Lee, Chung-Gyu Park, SuJin Cho, andSoung-Hoo Jeon

Volume 26, Number 1

Original Contributions

Identification of Donor Origin and Condition of Transplanted IsletsIn Situ in the Liver of a Type 1 Diabetic Recipient 1Cornelis R. van der Torren, Jessica S.Suwandi,DaHae Lee, Ernst-Jan T.vant Wout, GabyDuinkerken,Godelieve Swings,Arend Mulder, Frans H. J.Claas,Zhidong Ling, Pieter Gillard, BartKeymeulen, Peterint Veld, and Bart O.Roep

Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response 11Christopher A. Adin, Zachary C.VanGundy, Tracey L. Papenfuss, Feng Xu, MostafaGhanem, JonathanLakey, and Gregg A. Hadley

Active Subjects With Autoimmune Type 1 Diabetes Have Better Metabolic Profiles Than Sedentary Controls 23M.Adamo, R.Codella, F. Casiraghi, A.Ferrulli, C.Macri, E.Bazzigaluppi, I.Terruzzi, L.Inverardi, C.Ricordi, and L.Luzi

Effect of Manufacturing Procedures on Human Islet Isolation From DonorPancreata Standardized by the North American Islet Donor Score 33Chun-Chieh Yeh, Ling-jia Wang, James J.McGarrigle, Yong Wang,Chien-Chang Liao, MustafaOmami, Arshad Khan, MohammadNourmohammadzadeh, Joshua Mendoza-Elias, Benjamin McCracken,Enza Marchese, BarbaraBarbaro, and JoseOberholzer

Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats 45Lu Liang,Zongjin Li, Tao Ma,Zhibo Han,Wenjing Du,Jie Geng,Honghong Jia, Meng Zhao,Jimin Wang,Bingjing Zhang,Jie Feng,Lanzhen Zhao, AlainRupin,Youwei Wang, andZhong Chao Han

Excluding Anti-cytomegalovirus Immunoglobulin M-Positive Cord Blood Units Has a Minimal Impact on the Korean Public Cord Blood Bank Inventory 63Sue Shin,Eun Youn Roh,Sohee Oh,Eun Young Song,Eui Chong Kim, and Jong Hyun Yoon

Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin 71Elisabet Gustafson, Sana Asif, HudaKozarcanin, GracielaElgue,Staffan Meurling, Kristina N.Ekdahl, and Bo Nilsson

Poor Mobilization in T-Cell-Deficient Nude Mice Is Explained by Defective Activation of Granulocytes and Monocytes 83MarcinWysoczynski, MateuszAdamiak,Malwina Suszynska, Ahmed Abdel-Latif, JaninaRatajczak, andMariusz Z.Ratajczak

Differences inTfh Cell Response Between the Graft and Spleen With Chronic Allograft Nephropathy 95Jian Shi,Xianlin Xu,Fengbao Luo,Qianqian Shi,Xiaozhou He, and Ying Xia

Improved Transplanted Stem Cell Survival in a Polymer Gel Supplemented With Tenascin C Accelerates Healing and Reduces Scarring of Murine Skin Wounds 103Cecelia C. Yates, AustinNuschke, Melanie Rodrigues, Diana Whaley, Jason J.Dechant, Donald P. Taylor, and Alan Wells

Effect of Gelatin on Osteogenic Cell Sheet Formation Using Canine Adipose-Derived Mesenchymal Stem Cells 115Ah young Kim,Yongsun Kim,Seung Hoon Lee,Yongseok Yoon, Wan-Hee Kim, and Oh-Kyeong Kweon

Biliary Polyunsaturated Fatty Acids andTelocytes in Gallstone Disease 125Artur Pasternak,Jolanta Bugajska,Mirosaw Szura, Jerzy A.Walocha, AndrzejMatyja,Mariusz Gajda, KrystynaSztefko, and Krzysztof Gil

Cellular Evidence ofTelocytes as Novel Interstitial Cells Within the Magnum of Chicken Oviduct 135Ping Yang,Xudong Zhu,Lingling Wang,Nisar Ahmed,Yufei Huang, Hong Chen, Qian Zhang,Shakeeb Ullah,Tengfei Liu,Dawei Guo,Sarfaraz AhmedBrohi, andQiusheng Chen

Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats 145So YoonAhn, Yun Sil Chang, Dong Kyung Sung, Se In Sung,Jee-YinAhn, and Won Soon Park

Intramyocardially Transplanted Neonatal Cardiomyocytes (NCMs) Show Structural and Electrophysiological Maturation and Integration and Dose-Dependently Stabilize Function of Infarcted Rat Hearts 157MartinaMaass, BenjaminKrausgrill, SimonEschrig, TobiasKaluschke,Katja Urban, GabrielPeinkofer, Tobias G.Plenge, SimonOeckenpohler, MartinRaths, DennisLadage, MarcelHalbach,Jurgen Hescheler, andJochen Muller-Ehmsen

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Cell Transplantation : The Regenerative Medicine Journal

The Nobel Prize in Physiology or Medicine for 2001 – Press …

8 October 2001

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2001 jointly to&

Leland H. Hartwell, R. Timothy (Tim) Hunt and Paul M. Nurse

for their discoveries of "key regulators of the cell cycle"

All organisms consist of cells that multiply through cell division. An adult human being has approximately 100 000 billion cells, all originating from a single cell, the fertilized egg cell. In adults there is also an enormous number of continuously dividing cells replacing those dying. Before a cell can divide it has to grow in size, duplicate its chromosomes and separate the chromosomes for exact distribution between the two daughter cells. These different processes are coordinated in the cell cycle.

This year's Nobel Laureates in Physiology or Medicine have made seminal discoveries concerning the control of the cell cycle. They have identified key molecules that regulate the cell cycle in all eukaryotic organisms, including yeasts, plants, animals and human. These fundamental discoveries have a great impact on all aspects of cell growth. Defects in cell cycle control may lead to the type of chromosome alterations seen in cancer cells. This may in the long term open new possibilities for cancer treatment.

Leland Hartwell (born 1939), Fred Hutchinson Cancer Research Center, Seattle, USA, is awarded for his discoveries of a specific class of genes that control the cell cycle. One of these genes called "start" was found to have a central role in controlling the first step of each cell cycle. Hartwell also introduced the concept "checkpoint", a valuable aid to understanding the cell cycle.

Paul Nurse (born 1949), Imperial Cancer Research Fund, London, identified, cloned and characterized with genetic and molecular methods, one of the key regulators of the cell cycle, CDK (cyclin dependent kinase). He showed that the function of CDK was highly conserved during evolution. CDK drives the cell through the cell cycle by chemical modification (phosphorylation) of other proteins.

Timothy Hunt (born 1943), Imperial Cancer Research Fund, London, is awarded for his discovery of cyclins, proteins that regulate the CDK function. He showed that cyclins are degraded periodically at each cell division, a mechanism proved to be of general importance for cell cycle control.

Cells having their chromosomes located in a nucleus and separated from the rest of the cell, so called eukaryotic cells, appeared on earth about two billion years ago. Organisms consisting of such cells can either be unicellular, such as yeasts and amoebas, or multi-cellular such as plants and animals. The human body consists of a huge number of cells, on the average about one billion cells per gram tissue. Each cell nucleus contains our entire hereditary material (DNA), located in 46 chromosomes (23 pairs of chromosomes).

It has been known for over one hundred years that cells multiply through division. It is however only during the last two decades that it has become possible to identify the molecular mechanisms that regulate the cell cycle and thereby cell division. These fundamental mechanisms are highly conserved through evolution and operate in the same manner in all eukaryotic organisms.

The cell cycle consists of several phases (see figure). In the first phase (G1) the cell grows and becomes larger. When it has reached a certain size it enters the next phase (S), in which DNA-synthesis takes place. The cell duplicates its hereditary material (DNA-replication) and a copy of each chromosome is formed. During the next phase (G2) the cell checks that DNA-replication is completed and prepares for cell division. The chromosomes are separated (mitosis, M) and the cell divides into two daughter cells. Through this mechanism the daughter cells receive identical chromosome set ups. After division, the cells are back in G1 and the cell cycle is completed.

The duration of the cell cycle varies between different cell types. In most mammalian cells it lasts between 10 and 30 hours. Cells in the first cell cycle phase (G1) do not always continue through the cycle. Instead they can exit from the cell cycle and enter a resting stage (G0).

For all living eukaryotic organisms it is essential that the different phases of the cell cycle are precisely coordinated. The phases must follow in correct order, and one phase must be completed before the next phase can begin. Errors in this coordination may lead to chromosomal alterations. Chromosomes or parts of chromosomes may be lost, rearranged or distributed unequally between the two daughter cells. This type of chromosome alteration is often seen in cancer cells.

It is of central importance in the fields of biology and medicine to understand how the cell cycle is controlled. This year's Nobel Laureates have made seminal discoveries at the molecular level of how the cell is driven from one phase to the next in the cell cycle.

Leland Hartwell realized already at the end of the 1960s the possibility of studying the cell cycle with genetic methods. He used baker's yeast, Saccharomyces cerevisiae, as a model system, which proved to be highly suitable for cell cycle studies. In an elegant series of experiments 1970-71, he isolated yeast cells in which genes controlling the cell cycle were altered (mutated). By this approach he succeeded to identify more than one hundred genes specifically involved in cell cycle control, so called CDC-genes (cell division cycle genes). One of these genes, designated CDC28 by Hartwell, controls the first step in the progression through the G1-phase of the cell cycle, and was therefore also called "start".

In addition, Hartwell studied the sensitivity of yeast cells to irradiation. On the basis of his findings he introduced the concept checkpoint, which means that the cell cycle is arrested when DNA is damaged. The purpose of this is to allow time for DNA repair before the cell continues to the next phase of the cycle. Later Hartwell extended the checkpoint concept to include also controls ensuring a correct order between the cell cycle phases.

Paul Nurse followed Hartwell's approach in using genetic methods for cell cycle studies. He used a different type of yeast, Schizosaccharomyces pombe, as a model organism. This yeast is only distantly related to baker's yeast, since they separated from each other during evolution more than one billion years ago.

In the middle of the 1970s, Paul Nurse discovered the gene cdc2 in S. pombe. He showed that this gene had a key function in the control of cell division (transition from G2 to mitosis, M). Later he found that cdc2 had a more general function. It was identical to the gene ("start") that Hartwell earlier had identified in baker's yeast, controlling the transition from G1 to S.

This gene (cdc2) was thus found to regulate different phases of the cell cycle. In 1987 Paul Nurse isolated the corresponding gene in humans, and it was later given the name CDK1 (cyclin dependent kinase 1). The gene encodes a protein that is a member of a family called cyclin dependent kinases, CDK. Nurse showed that activation of CDK is dependent on reversible phosphorylation, i.e. that phosphate groups are linked to or removed from proteins. On the basis of these findings, half a dozen different CDK molecules have been found in humans.

Tim Hunt discovered the first cyclin molecule in the early 1980s. Cyclins are proteins formed and degraded during each cell cycle. They were named cyclins because the levels of these proteins vary periodically during the cell cycle. The cyclins bind to the CDK molecules, thereby regulating the CDK activity and selecting the proteins to be phosphorylated.

The discovery of cyclin, which was made using sea urchins, Arbacia, as a model system, was the result of Hunt's finding that this protein was degraded periodically in the cell cycle. Periodic protein degradation is an important general control mechanism of the cell cycle. Tim Hunt later discovered cyclins in other species and found that also the cyclins were conserved during evolution. Today around ten different cyclins have been found in humans.

The three Nobel Laureates have discovered molecular mechanisms that regulate the cell cycle. The amount of CDK-molecules is constant during the cell cycle, but their activities vary because of the regulatory function of the cyclins. CDK and cyclin together drive the cell from one cell cycle phase to the next. The CDK-molecules can be compared with an engine and the cyclins with a gear box controlling whether the engine will run in the idling state or drive the cell forward in the cell cycle.

Most biomedical research areas will benefit from these basic discoveries, which may result in broad applications within many different fields. The discoveries are important in understanding how chromosomal instability develops in cancer cells, i.e. how parts of chromosomes are rearranged, lost or distributed unequally between daughter cells. It is likely that such chromosome alterations are the result of defective cell cycle control. It has been shown that genes for CDK-molecules and cyclins can function as oncogenes. CDK-molecules and cyclins also collaborate with the products of tumour suppressor genes (e.g. p53 and Rb) during the cell cycle.

The findings in the cell cycle field are about to be applied to tumour diagnostics. Increased levels of CDK-molecules and cyclins are sometimes found in human tumours, such as breast cancer and brain tumours. The discoveries may in the long term also open new principles for cancer therapy. Already now clinical trials are in progress using inhibitors of CDK-molecules.

This year's Nobel Laureates, using genetic and molecular biology methods, have discovered mechanisms controlling the cell cycle. CDK-molecules and cyclins drive the cell from one phase to the next. The CDK-molecules can be compared with an engine and the cyclins with a gear box controlling whether the engine will run in the idling state or drive the cell forward in the cell cycle.

See also high resolution images:

Cell cycle, English version Cellcykel, Swedish version Leland H. Hartwell R. Timothy (Tim) Hunt Paul M. Nurse

To cite this page MLA style: "The Nobel Prize in Physiology or Medicine for 2001 - Press Release". Nobelprize.org. Nobel Media AB 2014. Web. 8 Jun 2017. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/press.html>

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CAR T-cell therapy Why it’s too soon to speculate about a ‘cure’ for multiple myeloma – HealthNewsReview.org

Kathlyn Stone is an associate editor at HealthNewsReview.org. She tweets as @KatKStone.

An experimental immunotherapy treatment for multiple myeloma from a biotech company in China captured wide attention at the just-concluded American Society of Clinical Oncology (ASCO) meeting.

Weve been following news reports from the meeting closely since it kicked off last Friday:

ASCOs news release on the new treatment, a form of CAR T-cell therapy, noted that the phase 1 results are preliminary and that the small trial was short-term. But then it blew past those cautions by speculating that the treatment could send multiple myeloma into long-term remission and might represent a cure for this incurable disease. The treatment costs werent included, either.

Andrae Vandross, MD, a hematology/oncology fellow at UCLA and a contributor to HealthNewsReview.org, said the news release had some important details, such as a discussion of adverse events, particularlycytokine release syndrome (CRS), which affected many patients.

But overall, I wish more attention was paid to the fact that this small trial was to examine safety and efficacy and that much more needs to be done to make statements regarding clinically meaningful impact on disease, Vandross said.

The shortcomings of the news release can be found repeated in some of the news coverage.

Reuterss story, Chinese cell therapy effective in small multiple myeloma trial didnt explain harms well nor mention costs.

FierceBiotechs article played up the horse race aspect of the pharmaceutical industry where competing companies race to get media and investor attention for their preliminary research, ASCO dark horse Nanjing Legend Biotech shines with promising CAR-T data. But costs didnt make it into the discussion.

Nor was the price tag mentioned in The Scientists piece, CAR T-Cell trials boast promising results.

Deborah Korenstein, MD, an internist at Memorial Sloan-Kettering Cancer Center, who did attend the meeting, found some of the reports on the CAR-T study lacking.

None of these articles mentions cost, though CAR-T therapy is very expensive. They do note that the follow-up is short-term so far, though they also talk about long-term remission (in the case of the Reuters piece) or cure (in the ASCO press release), which at the very least sends a mixed message.

NBC News piece, CAR-T Cancer Approach Has Surprising Success in Multiple Myeloma, reflects some of this mixed messaging.After reporting that the results were impressive and remarkable and that the study brings hope of a possible cure, the NBC story eventually broaches the issues of adverse effects and costs: The treatment is expected to cost $200,000 to $300,000, and whos going to pay for that is a big issue, according to a study author.

What does Korenstein think news organizations and public relations people could do better?

Stick to the evidence at hand, avoid speculating about outcomes that havent been determined, and make sure that potential harms are described as thoroughly as benefits.

Certainly there is no evidence so far to support those claims about longer term outcomes. They say it in a hedgy way but to me they shouldnt be mentioning it at all. They also play down the fact that the huge majority of patients had CRS, even if it was often not severe which is generally defined as requiring hospitalization. Its not clear here what severe means.

Dr. Korenstein disclosed that her spouse consults for Vedanta Biosciences.

Kevin Lomangino is the managing editor of HealthNewsReview.org. He tweets as @KLomangino. You'll be tempted

This week we begin a slow roll-out of a new offer of help to those

Today kicks off the annual meeting of the American Society of Clinical Oncology, the world's

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Novartis touts new T-cell therapy data in race for FDA approval – Reuters

ZURICH Novartis on Wednesday touted new data from its T-cell therapy CTL019, saying it is on a par with results of experimental molecules from Kite Pharma and Juno Therapeutics that also target aggressive blood cancers.

Three months after infusion, the overall response rate (ORR)among 51 adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was 45 percent, Novartis said, with 37 percent complete responses (CR), or no sign of disease.

Novartis aims for $1 billion in annual sales for CTL019, a drug made by taking T cells from a patient, reprogramming them in the lab to fight cancer, and re-infusing them. The field is crowded, with Kite and Juno also hunting for approval for drugs whose per-patient costs could top $500,000.

"When you look across the three competitors' data sets, they're all in a similar range of responses," Novartis drug development chief Vas Narasimhan said in an interview. "What's critical is to see the data sets fully mature... and look at the overall safety profile."

Narasimhan said no deaths were linked to CTL019, though three patients died from disease progression within 30 days of infusion. Seven suffered severe neurological events.

While so-called "CAR-T therapies" from Novartis, Kite and Juno are now last resorts for patients who have failed other treatments, more doctors are growing convinced they have promise. Globally, there are some 183 CAR-T trials underway.

In March, Novartis filed CTL019 with the U.S. Food and Drug Administration for fast-track approval in B-cell acute lymphoblastic leukemia (ALL) in young patients. The FDA has scheduled a July 12 public meeting for that.

Novartis could file for FDA approval in DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in adults, around October, with European filings planned about the same time.

Rival Kite Pharma's experimental drug axi-cel is also under expedited U.S. review against advanced NHL, with additional trials underway in leukaemia patients.

Kite has said 41 percent of NHL patients responded to axi-cel treatment at the six-month cutoff, with 36 percent in complete response.

Though Juno Therapeutics has suffered significant setbacks -- patient deaths forced it to abandon its lead CAR-T molecule this year -- the company released fresh data last week on another drug, JCAR017, against NHL.

Novartis is studying why some patients respond to CTL019 while others' cancers avoid detection.

Additional trials are planned, including with newer CAR-Ts combined with other drugs.

"There's just a lot of science that's yet to be understood," Narasimhan said. "I hope we have better answers next year ... for what's going on in the non-responders."

(Reporting by John Miller, editing by Louise Heavens)

VIENTIANE Dozens of fertility clinics have mushroomed in land-locked Laos after scandals over commercial surrogacy have spurred wealthier southeast Asian neighbors to ban the controversial procedure since 2015.

Automakers could help prevent accidental deaths of small children left in hot cars by installing devices to remind drivers to check their back seats for passengers before getting out, three U.S. lawmakers sponsoring a safety measure said on Wednesday.

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Bioquark Hopes to Bring Dead Back to Life Using Stem Cell Therapy – India West

A Philadelphia-based company along with an Indian orthopedic surgeon has said it will start a new type of stem cell therapy that claims it can bring people back from the dead.

Bioquark, led by chief executive Ira Pastor, said it will begin conducting trials of the therapy later in the year in an undisclosed country in Latin America, according to a New York Post report.

Pastor and Indian orthopedic surgeon Himanshu Bansal had initially hoped to run tests in India in 2016 but the Indian Council of Medical Research pulled the plug on their plans and asked them to take the trials elsewhere, the Post reported.

Most countries officially declare someone dead when there is irreversible loss of brain function. The Bioquark therapy boasts it can reboot the brain.

The company said it will begin testing on humans, with no plans to experiment on animals.

Scientists plan to examine individuals aged between 15 and 65 who have been declared brain dead from a traumatic brain injury, the report noted, citing a published study.

The three-stage process starts with harvesting stem cells from the patients own blood before injecting them back into their body. Next, the patient is given a dose of peptides injected into their spinal cord. The final step is a 15-day course of laser and median nerve stimulation while monitoring the patient with MRI scans.

Bansal practices in New Delhi.

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Bioquark Hopes to Bring Dead Back to Life Using Stem Cell Therapy - India West

President Trump Reappoints NIH Director Francis Collins Who Supports Embryonic Stem Cell Research – LifeNews.com

President Donald Trump has decided to appoint the director of the National Institutes of Health even though pro-life advocates called on Francis Collins to be replaced because of his support for embryonic stem cell research that involves the destruction of human life.

Last month, 40 Republicans in the House of Representatives wrote president Trump urging him to get rid of NIH director Francis Collins because of his support for the practice, which is opposed by pro-life organizations.

While we deeply respect Dr. Collins Christian faith and commitment to public service, the stances that Dr. Collins has taken in the past regarding embryonic stem cell research and human cloning are not life-affirming and directly conflict with the pro-life direction of your new presidency, the GOP lawmakers wrote. It is because of this troubling paradox that we ask you to re-consider his leadership role at NIH.

While pro-life advocates strongly support scientific research, they oppose embryonic stem cell research because the only way to obtain embryonic stem cells is to destroy unique human beings just days after conception. On the other hand, ethical adult stem cell research has produced cures or treatments for well over 100 diseases or medical conditions and involves no destruction of human life. Embryonic stem cell research has still yet to treat a single human being successfully.

But Trump has decided to keep Collins in place:

Collins is a pioneer in the field of genetics who has directed the NIH since August 2009, after successfully leading the nations effort to map the human genome. He was among several dozen Obama administration officials who Trump aides had asked to stay in their jobs at least temporarily for the purpose of continuity.

Trump made the announcement about Collins on Tuesday.

The NIH is a division of the Department of Health and Human Services and is made up of 27 different institutes and centers. Its also known as the nations medical research agency.

Trump has proposed cutting the overall NIH budget from $31.8 billion to $26 billion.

Congressman Jim Banks of Indiana told LifeNews hes not happy about the decision.

Follow LifeNews.com on Instagram for pro-life pictures.

I am disappointed in the Trump Administrations decision to keep Dr. Francis Collins as head of the NIH. Dr. Collins support of embryonic stem cell research, along with his comments that cloned embryos do not deserve the same moral protections as naturally generated embryos, make him a less than an ideal fit for a pro-life administration. I am hopeful that Dr. Collins will turn away from embryo-killing research as he continues his tenure as NIH Director.

Collins has led the NIH since 2009, when he was unanimously confirmed by the Senate.

The Obama administration forced Americans to pay for embryonic stem cell research involving the destruction of human life. National Institutes of Health chief Francis Collins approved taxpayer funding of dozens of lines of embryonic stem cells. The cells can only be obtained by destroying unborn children days after conception at which point human embryos are unique human beings.

Obama issued an executive order overturning the limits President Bush put in place on any new embryonic stem cell research funding. Bush directed federal dollars mostly to adult stem cells that are already helping patients now.

The Family Research Council responded to the Obama administrations move by saying that adult stem cells are already helping diabetes patients.

Of course, when it comes to juvenile (type I) diabetes, adult stem cells have already shown success at treating diabetes patients, the pro-life group noted.

It added, Interestingly, none of the human embryonic stem cell lines approved thus far are from the original group of 21 lines that had been receiving NIH funding, only one (H1one of the original five Thomson lines) has been submitted for approval, with only two other lines from Cellartis supposedly to be submitted for review.

This is surprising given that the vast majority of human embryonic stem cell research has been done with those previous lines, thus forcing most embryonic stem cell researchers to start over on experiments with new lines the group continued.

It also shows that this gold rush is just that, an attempt to grab more money built on embryo destruction, not built on science, FRC concluded.

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Stem cell researcher takes on the brain’s fight against age-related diseases – USC News

What happens to the stem cells in our brains as we age? Albina Ibrayeva, a PhD student in the USC Stem Cell laboratory of Michael Bonaguidi, addresses this question as she tries to understand how the brain naturally fights against aging and suggests promising therapeutic avenues for treating age-related neurodegeneration, disease and disorders.

I love science. As an undergraduate student back in Kazakhstan, I constantly sought ways to put my knowledge into practice. During my sophomore year, I interned at the National Center for Biotechnology in Astana. This experience enabled me to work with some of the brightest minds dedicated to scientific research in my country and showed me the meaningfulness of a career in biomedical research. Since then, I knew that I wanted to be a scientist.

I won a scholarship and was accepted to graduate school at USC, first to study biomedical engineering as a masters student, then the biology of aging as a PhD student. In 2015, I joined Michael Bonaguidis lab. So here I am, excited and really passionate about contributing to a not-so-distant future where research and medicine advance all humans well-being.

USC is one of the worlds top research universities, especially for someone who is studying neuroscience, stem cells and aging. The synergy among the LAC-USC Medical Center, the Alzheimers Disease Research Center, the Geriatric Studies Center, the Alzheimers Therapeutic Research Institute, the Laboratory of NeuroImaging, the Zilkha Neurogenetic Institute and USCs stem cell research center provides one of the best avenues to do great research and advance clinical and basic science.

Not only I am blessed to work at USC, but also I like the fact that we are surrounded by the best universities, such as Caltech and the University of California campuses in L.A., San Diego, San Francisco and Santa Barbara with whom we collaborate. California is known to be the most progressive place on Earth in science, technology and innovation. That is why I think I am in the right place, where I too can contribute to science and research on aging and its effects.

After graduating from the USC PhD program, I would like to work as a professor and researcher at a U.S. university. It is one of my dreams to be able to share my knowledge and being a professor would allow me to do so, while continuing my research to benefit U.S. health care and the science of aging.

Research, of course, is and will remain a big part of my life. Science is there to help people who are suffering from different diseases and disorders. In particular, stem cell research has a great potential for its therapeutic application across fields. Science can be really challenging. However, at the same time it is really exciting, and I am a firm believer that science is changing and will change the world, if given a chance.

In high school, I was a professional volleyball player. But then I realized that I dont want to pursue a career in sports, but science.

Sometimes it is hard to stay active, especially when all day long you are analyzing your data, conducting experiments and running simulations on your computer. But whenever I have free time, I try to spend it being as active as possible. I try to hike at least once a week. The Santa Monica Mountains are the best place to hike, with their breathtaking views of the Pacific Ocean, native California grasslands, famous Malibu beaches, and even some historical and cultural sites of Native American life. This is what makes me happy outside of science.

More stories about: Aging, First-Generation Students, Research, Stem Cells

Newly arrived scientist contributes brain power to stem cell research at USC.

One of 11 new postdoctoral fellows receives support from USC and Mexicos equivalent of the National Science Foundation.

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Stem cell researcher takes on the brain's fight against age-related diseases - USC News

Sowing Stem Cells: Lab-Grown Organoids Hold Promise for Patient Treatments – UCSF News Services

Illustration by Camila Carlow

Ophir Klein is growing teeth,which is just slightly less odd than what Jeffrey Bush is growing tissues that make up the face. Jason Pomerantz is growing muscle; Sarah Knox is growing salivary glands; and Edward Hsiao is printing 3-D bone using a machine that looks about as complex as a clock radio.

Together, these members of the UC San Francisco facultyare cultivating organs of the craniofacial complex the skull and face which too often go terribly wrong during fetal development. Deformities of these bones or soft tissues, the most common of birth defects, can cut life short by blocking the airway or circulation. Or they can disfigure a face so profoundly that a child strugglesto see, hear, or talk. Perhaps most painful of all, such deformities render children physically other, potentially leading to a lifetime of corrective surgeries and social isolation.

As director of the UCSF Program in Craniofacial Biology, Klein orchestrates a multisite research endeavor to translate basic science findings in tissue regeneration into improved treatments for these kids. Using stem cells from patients with craniofacial deformities, Klein, Bush, Pomerantz, Knox, Hsiao, and their colleagues are growing tiny functioning segments of organs, called organoids, to figure out exactly when and how in fetal development such design flaws occur.

Read a digital flipbook of the entire summer issue of UCSF Magazine, featuring this and other stories.

They are among scientists across UCSF who are cultivating cellular systems such as miniature brains and breasts from patient cells. They serve as dioramas of disease models derived from human cells either displacing or complementing the mouse models that have served science well, though inexactly, for manyyears. The effort is one of the most obvious and viable payoffs to date from stem cell science. With these organoids, physicians and scientists can not only trace the pathways of normal and abnormal development, but also test drugs and other treatments for their effectiveness in humans. Organoids are also one tiny step toward the ultimate goal of generating complete organs, as a way to circumvent rejection issues and save the lives of those who now die waiting for transplants.

As the reservoirs of human development, stem cells take it upon themselves to tirelessly renew and differentiate into the myriad cell types required to build out a body from an embryo. In creating an organoid, typical construction metaphors do not apply. There are no building blocks to nail, stack, or solder and no job-site supervisor barking orders. Thats not how biology works, says Zev Gartner, PhD, an associate professor of pharmaceutical chemistry.

It is a self-organizing process, he explains, a process that starts in the womb with embryonic stem cells (ESCs) or, in the case of organoids, induced pluripotent stem cells (iPSCs). iPSCs are mature cells that are stripped back to their earliest stage of development using a process devised by UCSF Professor of Anatomy Shinya Yamanaka, MD, PhD, who won a Nobel Prize for discovering the process. To make organoids, iPSCs are put through a series of solutions, then added to a gel that mimics the squishy 3-D cellular matrix of the embryo. The gel provides the right conditions for them to get to work.

Take an organ like the lung. Its basic functional units are a tube and a sac, and outside that sac are capillaries that allow gas exchange. Hundreds of millions of tubes and sacs make a lung, explains Gartner. You can make the little sacs and the tubes in a dish as an organoid model. But we dont know how to drive the self-organization of those units into much more complex, elaborate, highly ramified structures. The fundamental limitation of organoids is that they lack the vasculature that brings nutrient-laden blood to fuel the evolution of the larger structure.

Gartner notes that people who work with stem cells tend to focus on either regenerative medicine or disease modeling. Those interested in disease make models of tissues so that they can understand how diseases work, while those interested in regenerative medicine try to make models of healthy tissue that couldbe transplanted. Gartner straddles both camps. He grows breast organoids. The mammary gland is great because we can simultaneously think about these two phenomena as two sides of the same coin, he says. One is regenerative medicine through self-organization, and the other is understanding the progression of breast cancer through a breakdown in self-organization.

So theres potentially a triple payoff in stem cell science: By deducing how a breast forms itself, Gartner might figure out how to grow the entire organ. By tracing how cancer throws a wrench in the works, he may be able to target ways to stop that process. And by growing a human organ in a dish, he avoids making cross-species assumptions or putting animals or humans at risk in testing potential drugs to cure breast cancer, greatly accelerating the push toward a cure.

On Kleins team, Jeffrey Bush, PhD, an assistant professor of cell and tissue biology, looks at organoids through the lens of disease.

The organoids he grows model craniofrontonasal syndrome a birth defect that is caused by a mutation in a single gene and that dramatically impacts the shape of the face and head. He knows from studies reproducing craniofrontonasal syndrome in mice that the first place something goes wrong is in a cell type called the neuroectoderm. To create an organoid to study this, he obtained skin cells from Pomerantz, an associate professor of surgery, who has patients with the syndrome who were willing to donate tissue samples. Such collaborations between basic scientists and clinicians are key to bringing research out of the lab and into patient care.

We studied this simple system to see how this mutation affected the organization of these cells, says Bush. His group has filmed cells as they rush about to self-organize when theyre mixed together. In those films, he explains, you can see that the mutated cells, which are dyed red, segregate from the normal cells, which are green they are like oil and water. In other words, the mutated cells completely disrupt the behavior of all the cells. By contrast, in the films of cells without the mutation, all the cells circulate easily among one another, like fish in an aquarium. This understanding has allowed Bush to begin to think about a drug that blocks this separation. He has several promising candidates that his team will test in pregnant mice. Right now, he says, there isnt a single drug that we can use for any kind of structural birth defects. If we could show that a medication blocks the effects of this mutation, it would serve as proof of principle that something besides surgery can be done. But we would have to know that it was safe for mother and child and that we could catch it early enough.

Jason Pomerantz, MD, a plastic surgeon, falls into the regeneration camp. His clinical work is typified by a recent eight-hour operationon a 17-year-old boy with Crouzon syndrome, a severely disfiguring condition affecting every organ in the craniofacial structure muscle, bone, and skin. My patient is excited for the outcome, but not about the process, says Pomerantz, surgical director of the UCSF Craniofacial Center. For three months, the patient will wear a large metal frame on his head with wires that will pull the bones in his face forward. Prior to the surgery, the boys face was nearly concave, collapsed inward at the nose.

Yet bone is not all Pomerantz needs to work with to restructure a face. The subtle bends, creases, and curves of expressionthat make a face ones own are the work of tiny muscles.Right now we can move a big muscle say, from the thighto the face so that people can smile, he says. But we cant reconstruct the fine ones that enable people to move their eyebrows up or move the eyeballs around. That requires little muscles. This is where we can make headway with stem cell biology.

We have actually made a humanized organ in an animal, he continues, pointing to a picture of a mouse on his wall. Pomerantz is now considering incubating small human muscles in animals for use in his patients faces. In a recent project, he inserted stem cells from human muscles into a mouse whose own muscle stem cells had been incapacitated. He then perturbed the muscle to stimulate regeneration. As the muscle healed, the cells created new muscle tissue, which the mouses nerves innervated to make a functioning muscle. Its exactly the size of the muscles Pomerantz needs for full articulation of expression and function in a human face or hand.

Muscles are part of a vast and intricate system strewn throughoutthe body. Teeth, on the other hand, are islands unto themselves. Teeth intrigue me from a regeneration perspective, says OphirKlein, MD, PhD, chair of the Division of Craniofacial Anomalies, the Hillblom Professor of Craniofacial Anomalies, the Epstein Professor of Human Genetics, and a resident alumnus. They are discrete organs all the parts are there. More intriguing still is the fact that many rodents have the ability to grow their front teeth continuously. Elephants and walruses also have ever-growing tusks, and even some primates lemurs can regrow their teeth.

In studying species that can [regrow teeth], we hope to unlock the regenerative potential in our own cells.

Ophir Klein, MD, PhD

Chair of the Division of Craniofacial Anomalies

A tooth can be regenerated in parts. Stem cells can be used to grow the root, and then a crown can be added to complete the tooth. To generate a whole organ at once, Kleins colleagues are planning to partner with bioengineers who can produce a biocompatible material that could serve as a framing device to jump-start the creation of dentin, one of the hard components of a tooth. If they start with the right cells, then the scaffolding will give the cellsthe shape information they need to create the right design. But even that isnt Kleins endgame. In my lab, were interested in figuring out why humans cant regrow teeth, he says. In studying species that can, we hope to unlock the regenerative potential in our own cells that might be turned off.

Kleins work to generate teeth is inspired by his patients with ectodermal dysplasia, a congenital disorder characterized by lack of sweat glands, hair, or teeth. Being able to generate the roots of teeth would be remarkable for these patients, since the rest can be done with a crown. Right now, they must be fitted with dentures.

Klein is also taking another tack to help these patients. We completed a clinical trial of a drug that basically goosed up the development of the organs when they werent forming properly, he says. The drug a protein developed by Swiss collaborators of Kleins, based on studies of embryonic mice, who develop theseorgans in early- to mid-gestation was given to infants with the disorder right after birth. The trial was unsuccessful. Now, scientists in Germany are running a trial of the same drug, giving it instead to mothers carrying babies with this genetic disorder. The scientists will try to gauge what the best timing is for delivering the drug.

Whats great about this drug is that it doesnt seem to have any effects on any other organs besides teeth,hair, and sweat glands, says Klein. Drugs for other conditions are far riskier, because they affect pathways that are important inthe development of many organs.

Sarah Knox, PhD, an assistant professor of cell and tissue biology, is using stem cells to figure out howto regenerate salivary glands compromised by radiation treatments for head and neckcancers or by craniofacial deformities. Her focus is on how the environment contributes to the activation and maintenance ofthe gland. The salivary gland, like all organs, is continuously replenishing the supply ofcells and tissues it needs to function. Knoxs research shows that the gland takesdirectional cues from nearby nerve cells not only to remain functional, but also to continuously replace itself. Her organoids are made of cells from a patient and nerve cells (ganglia) from a fetal mouse. We are trying to explore the relationship between the stem cells and the nerves, she says. How do the nerves know the tissue is there? How do the nerves provide instruction and feedback? Individual cells die off and new cells have to replace them. Organoids are giving us insight as to where those new cells are coming from and how we keep repopulating [them] all our lives.

As head of the UCSF Program in Craniofacial Biology which is based in the School of Dentistry and the Division of Genetics in the School of Medicine Klein stands at one of sciences most compelling crossroads: regenerative medicine and genetics. Far in the future, both fields have potential that seem like science fiction today. We live in a world where people die waiting for organ transplants. What if we could pull these organoids from their petri dish and supply them with the fuel they need to become full-blown organs? Such a feat would necessitate either a host embryo perhaps from apig, because pigs have organs the size of human organs or some other biological foundation. Some scientists are hoping to jump-start organ development with scaffolding, or cells engineered to speed the developmental process. Others are zeroing in on the genome, particularly in kids with craniofacial anomalies caused by just one mutation, like craniofrontonasal syndrome; for example, a tool called CRISPR could allow scientists to splice that gene out and replace it with a normal gene. But the tool has yet to be used in humans, let alone a human fetus.

Ethical questions pepper either route. At their best, stem cells regenerate tissues; at their worst, they go rogue and grow into a tumor. Yet with gene editing tools like CRISPR, you literally have the potential to change the species, says Klein. And in both scenarios, the cells can act with unforeseen off-target effects. Klein and his colleagues are in continual discussion about the repercussions of their work with the director of UCSF Bioethics, Barbara Koenig, RN, PhD 88. Gene therapy is an example of an exciting new treatment that cured one serious pediatric illness severe combined immunodeficiency syndrome (SCID) but the genes unwittingly led to the development of leukemia, explains Koenig. Genetic and stem cell interventions must be painstakingly studied before application. And, once they are ready, who will regulate them? Thereare many questions yet to be answered. The challenges are most extreme when we talk about modifying an egg or sperm cell, where the changes are passed on to the next generation.

So Klein and his colleagues proceed with caution, curiosity, and awe. The next decade will be an incredibly exciting time, says Klein. With continual advances in human genetics and developmental and cell biology, we hope to be able to make drugs and use genetic tools to appreciably change the lives of our patients.

Bone grows like a runaway train in Edward Hsiaos patients with fibrodysplasia ossificans progressiva (FOP). The slightest bump or injury can set off a spurt of bone growth that can fuse their vertebrae, lock their joints, or even freeze up their rib cages, leaving them unable to breathe.

No one, to date, has successfully engineered bone. Hsiao, MD, PhD, is hoping to spark the process with the help of a 3-D printer from Organovo, a firm that specializes in bioprinting technology. From iPSCs, he can make many of the essential ingredients of bone, including mesenchymal stem cells, endothelial cells, and macrophages. We are putting cells into the equivalent of an ink. Then we will print the structures with the ink, let the ink dissolve, and leave the cells, explains Hsiao. The hope is that the cells can then recapitulate the normal developmental process.

If the approach is successful, Hsiao hopes to use the resulting models to test drugs and other treatments to halt or prevent bone deformities. Down the line, his progress also stands to transform bone and joint replacements. Through his work with FOP, hes uncovered one mechanism that drives rapid bone growth. In these patients, we know that mature bone formation can happen in as quickly as two weeks, so it is possible to grow bone in an adult. We need to understand how to modulate that, says Hsiao. Someday, my dream would be to be able to identify the cells we need, give someone a drug that induces the right genes and recruits the right cells to the correct site, and have the cells rebuild the joint from scratch.

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Sowing Stem Cells: Lab-Grown Organoids Hold Promise for Patient Treatments - UCSF News Services

Does the sex of a cell matter in research? – News from Tulane

Dr. Franck Mauvais-Jarvis is a leading voice in the debate to bring sex parity to pre-clinical research. Photo by Paula Burch-Celentano.

Over the last decade, many drugs that have been pulled from the market due to toxicity were withdrawn because they affected women more than men. It turns out, the studies that brought the drugs to market were designed using only male cells and animal models, a common flaw a Tulane endocrinologist is working to help correct. We really need to study both sexes, says Dr. Franck Mauvais-Jarvis, a leading voice in the debate to bring sex parity to pre-clinical research. The focus on a single sex threatens to limit the impact of research findings as results may be relevant to only half of the population. Mauvais-Jarvis, a professor of endocrinology at Tulane University School of Medicine, is the lead author of a newly published article in the journal Cell Metabolism to help scientists who study obesity, diabetes or other metabolic diseases better account for inherent sex differences in research. While the National Institutes of Health recently mandated researchers consider sex as a biological variable by including both sexes in pre-clinical research, there is little guidance in designing studies to fully consider sex differences in underlying biological mechanisms. The article outlines the causes of sex differences in research models and the methods for investigators to account for these factors. Mauvais-Jarvis goal is to help investigators better understand that sex differences are not simply a superficial aspect of research that only account for different sets of hormones. He maintains that male and female are two different biological systems. Sex differences are at the core of the mechanism for biological traits and disease, Mauvais-Jarvis says. We believe that the incorporation of appropriately designed studies on sex differences in metabolism and other fields will accelerate discovery and enhance our ability to treat disease. This is the fundamental basis of precision medicine. The article is co-authored by Drs. Arthur Arnold and Karen Reue, two experts in the genetics of sex differences at the University of California, Los Angeles.

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Does the sex of a cell matter in research? - News from Tulane

Type of sugar may treat atherosclerosis, mouse study shows – Washington University School of Medicine in St. Louis

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Trehalose triggers cellular housekeeping in artery-clogging plaque

A new study shows that a type of natural sugar called trehalose triggers an important cellular housekeeping process in immune cells that helps treat atherosclerotic plaque. The image shows a cross section of a mouse aorta, the main artery in the body, with a large plaque. Straight red lines toward the upper left are the wall of the aorta. Yellow areas are where housekeeping cells called macrophages are incinerating cellular waste.

Researchers have long sought ways to harness the bodys immune system to treat disease, especially cancer. Now, scientists have found that the immune system may be triggered to treat atherosclerosis and possibly other metabolic conditions, including fatty liver disease and type 2 diabetes.

Studying mice, researchers at Washington University School of Medicine in St. Louis have shown that a natural sugar called trehalose revs up the immune systems cellular housekeeping abilities. These souped-up housecleaners then are able to reduce atherosclerotic plaque that has built up inside arteries. Such plaques are a hallmark of cardiovascular disease and lead to an increased risk of heart attack.

The study is published June 7 in Nature Communications.

We are interested in enhancing the ability of these immune cells, called macrophages, to degrade cellular garbage making them super-macrophages, said senior author Babak Razani, MD, PhD, an assistant professor of medicine.

Macrophages are immune cells responsible for cleaning up many types of cellular waste, including misshapen proteins, excess fat droplets and dysfunctional organelles specialized structures within cells.

In atherosclerosis, macrophages try to fix damage to the artery by cleaning up the area, but they get overwhelmed by the inflammatory nature of the plaques, Razani explained. Their housekeeping process gets gummed up. So their friends rush in to try to clean up the bigger mess and also become part of the problem. A soup starts building up dying cells, more lipids. The plaque grows and grows.

In the study, Razani and his colleagues showed that mice prone to atherosclerosis had reduced plaque in their arteries after being injected with trehalose. The sizes of the plaques measured in the aortic root were variable, but on average, the plaques measured 0.35 square millimeters in control mice compared with 0.25 square millimeters in the mice receiving trehalose, which translated into a roughly 30 percent decrease in plaque size. The difference was statistically significant, according to the study.

The effect disappeared when the mice were given trehalose orally or when they were injected with other types of sugar, even those with similar structures.

Found in plants and insects, trehalose is a natural sugar that consists of two glucose molecules bound together. It is approved by the Food and Drug Administration for human consumption and often is used as an ingredient in pharmaceuticals. Past work by many research groups has shown trehalose triggers an important cellular process called autophagy, or self-eating. But just how it boosts autophagy has been unknown.

In this study, Razani and his colleagues show that trehalose operates by activating a molecule called TFEB. Activated TFEB goes into the nucleus of macrophages and binds to DNA. That binding turns on specific genes, setting off a chain of events that results in the assembly of additional housekeeping machinery more of the organelles that function as garbage collectors and incinerators.

Trehalose is not just enhancing the housekeeping machinery thats already there, Razani said. Its triggering the cell to make new machinery. This results in more autophagy the cell starts a degradation fest. Is this the only way that trehalose works to enhance autophagy by macrophages? We cant say that for sure were still testing that. But is it a predominant process? Yes.

The researchers are continuing to study trehalose as a potential therapy for atherosclerosis, especially since it is not only safe for human consumption but is also a mild sweetener. One obstacle the scientists would like to overcome, however, is the need for injections. Trehalose likely loses its effectiveness when taken orally because of an enzyme in the digestive tract that breaks trehalose into its constituent glucose molecules. Razani said the research team is looking for ways to block that enzyme so that trehalose retains its structure, and presumably its function, when taken by mouth.

This work was supported by grants from the National Institutes of Health (NIH), grant numbers K08 HL098559 and R01 HL125838; the Washington University Diabetic Cardiovascular Disease Center and Diabetes Research Center, grant number P30 DK020579; The Foundation for Barnes-Jewish Hospital; and the Wylie Scholar Award from the Vascular Cures Foundation.

Sergin I, Evans TD, Zhang X, Bhattacharya S, Stokes CJ, Song E, Ali S, Dehestani B, Holloway KB, Micevych PS, Javaheri A, Crowley JR, Ballabio A, Schilling JD, Epelman S, Weihl CC, Diwan A, Fan D, Zayed MA, Razani B. Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis. Nature Communications. June 7, 2017.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Type of sugar may treat atherosclerosis, mouse study shows - Washington University School of Medicine in St. Louis