Stem Cell Clinic

Dual-Targeted CAR-T Therapies in Solid Tumors: Q&A With Dr Wayne Marasco – Cancer Therapy Advisor

By adminSeptember 24, 2019Uncategorized

The dawn of chimeric antigen receptor (CAR) T-cell (CAR-T) therapies ushered in a period of intense medical innovation. Despite this, researchers are still struggling with translating the success seen with CAR-T in hematologic malignancies into the area of solid tumors.

Wayne Marasco, MD, PhD, professor in the department of cancer immunology at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, is investigating the use of CAR-T in triple negative breast cancer (TNBC) and ovarian cancer. His lab, in collaboration with the Dana-Farber Cancer Institute, entered into an exclusive option with OncoSec for the company to license the product candidates and the associated intellectual property resulting from the research coming out of the Marasco lab using engineered single-chain variable fragment (scFv) antibodies in a dual-targeted bispecific CAR T-cell approach.1

His interests include marrying stimulatory cytokines and anti-inhibitory antibodies to break through the hostile tumor microenvironment that exists in solid tumors. To do this, he envisions using the local delivery of CAR-T cells to restore local antitumor immunity in the tumor microenvironment, and then allowing educated T cells to get out of the tumor cells so they can contribute to a systemic immune surveillance system that may help cells throughout the body persist against cancer for the long term.

Cancer Therapy Advisor sat down to speak to Dr Marasco to find out if he thinks CAR-T therapies should be categorized as cell or gene therapies, the feasibility of the approaches that can be used to deliver CAR-T payloads, and how dual-targeting CAR-Ts could be the one of the most durable options across adoptive cell therapy approaches.

This interview has been lightly condensed and edited for the purpose of clarity.

Cancer Therapy Advisor (CTA): Im curious about the use of a vaccine boost with CAR-T theres new research thats been out with other teams that combines the 2, and I was wondering how that works and if you could explain it.

Dr Marasco: So, first of all, I havent made it through the Ma et al. paper2 in great detail Lets just talk about the big picture, and that is that CAR-T cells can deliver payloads.

What may not be evident from what youve read from the press releases,1 and the internal information, is that we have designed CAR-T cell factories. So, theyre not just CAR-T cells, the whole basis of the work that we do is deliver payloads. So, the CAR-T cells not only get to the tumor in an antigen-specific way and thats where the dual targeting comes in once they get there, they secrete molecules locally, at the tumor site, to change the tumor microenvironment.

In the case of the vaccine boost, its really that concept that youre allowing molecules get to antigen-presenting cells to be able to boost the local immunity there. So, I havent been able to get through the paper in detail yet, but thats, basically, the 64,000-foot view of what theyre trying to do.

So, the idea of using CAR-T cells to deliver payloads, and to change the tumor microenvironment is inherent in the approach that is now published in this vaccine paper, as well as the work that we do, which is to change the tumor microenvironment in a different way the end result being restoration of immunities so that educated T cells that get to the tumor, that cant do anything because they are suppressed, become unsuppressed, if you will, and restore local antitumor immunity.

CTA: Based on the press release that I read [about the partnership with OncoSec, The Marasco Laboratory, and the Dana-Farber Cancer Institute], some candidates were mentioned in that release. Could you share which ones they are?

Dr Marasco: Were not releasing the targets yet because the work is still fairly early on, and we dont want to disclose what the actual targets that were doing are. The diseases that were looking at, I think, are fair game, and to that question, thats triple-negative breast cancer, as well as ovarian cancer, which was not mentioned in the press release, but thats the other cancer that were working on for the team so, 2 womens cancers.

CTA: There was a mention of the [use of OncoSecs] intratumoral TAVO IL-12, that would help facilitate getting the actual engineered CAR-T cells into the tumor microenvironment. How does that work, and also, how does that keep them persistent in that microenvironment?

Dr Marasco: So, the data (OncoSecs and the science that led to it) really show that IL-12 is a pretty potent cytokine to enhance T-cell stimulation, and I think the fact that theyre getting the clinical responses that they are shows that its working when injected locally perhaps systemically, but certainly locally. So, the idea there is that that, in and of itself, is changing the tumor microenvironment.

The limitations of it, of course, are that its a plasma-based therapy, so that when you do your local electroporation, youre getting the IL-12 gene taken up by the cells that are being electroporated, secreting that locally, thats enhancing the entire local immune system, including recruitment of white blood cells. And to an extent thats not totally worked out, because we just dont have enough data yet to carve it in stone, is that theyre also changing the tumor microenvironment. So, the concept here is that whatever boost that we can get in the tumor microenvironment to be able to let those CAR-T cells work more potently, would be an added benefit.

So, for example, in our case, the work that weve published so far has looked at the PD-1/PD-L1 axis by secluding antiPDL-1 locally at the tumor site. So, we know from many clinical trials now that that is certainly 1 of the keystones in the tumor microenvironment, that particular axis, but it doesnt work 100% in patients, and it varies depending on the tumor, and a number of other factors. So, PD-L1/PD-1, and CTLA-4 are 2 of the cornerstones in that they, in themselves, may not be enough.

So, those 2 axes that have led to the whole breakthrough in the field, are really to put on the brakes of suppressive molecules. Theyre not costimulatory; theyre blocking inhibitory pathways. So, when you look at the tumor microenvironment, and the whole way T cells get stimulated, theres a number of molecules that suppress T-cell stimulation, and theres a number of molecules that stimulate it. So, with therapy support, you only gain reverse in suppression. So, the idea of IL-12 is that it would be stimulatory.

If you combined a stimulatory cytokine, with the correct T cell thats secreting anti-inhibitory antibodies, you may be able to get marked change in the tumor microenvironment, and therefore lead to a significant increase in T-cell simulation. So, thats the idea between marrying the 2 therapies.

Healthy bone marrow may be important in fertility – BioNews

By adminSeptember 24, 2019Uncategorized

23 September 2019

A study in mice suggests that bone marrow-derived stem cells may play a role in establishing pregnancy.

The research showed that the stem cells can travel through blood circulation to the uterus, making it more receptive for a new embryo. Specifically, the authors showed that these cells concentrate in the lining of the uterus where the embryo is about to implant. There, they become specialised uterine cells or decidual cells, which are critical for maintaining the embryo.

'We have always known that two kind of things were necessary for pregnancy: you must have ovaries to make eggs, and you must also have a uterus to receive the embryo,' said senior author, Dr Hugh Taylor at Yale University in New Haven, Connecticut. 'But knowing that bone marrow has a significant role is a paradigm shift.'

Previous studies had shown that small numbers of bone-marrow stem cells contribute to the renewal of the lining of the non-pregnant uterus, but it remained unknown whether they play a part in pregnancy.

This study is the first to show a physiological role for bone-marrow stem cells in pregnancy.

This work was possible due to a methodological breakthrough. Dr Taylor and his team at Yale were able to develop a mild chemotherapy for their mouse model that 'wiped out' the bone marrow of these mice without affecting their eggs, and therefore their fertility. Then they fertilised these mice before and after healthy bone-marrow transplantation to investigate whether the bone-marrow stem cells contributed to the establishment of pregnancy.

The team also used mice that lack a protein called Hoxa11, usually expressed in both uterine and bone marrow progenitor cells - mice without this protein have a deficient womb and cannot become pregnant. Mice that only partially lack Hoxa11 can become pregnant, but they experience recurrent miscarriages. When these mice received bone marrow transplants from healthy mice, both sets were able to become pregnant. The partially-deficient mice went ahead to have as many pregnancies as their healthy mice.

Several studies have implicated Hoxa11 production and conditions that relate in pregnancy failure, such as endometriosis. The authors suggest further investigations for the role of Hoxa11 and bone-marrow stem cells in the human pregnancy and its establishment.

'We are currently translating these findings into humans to better understand the role that these bone marrow-derived stem cells play in recurrent implantation failure and recurrent pregnancy loss, two conditions that are unexplained in the majority of women and have no effective treatment,' said Dr Reshef Tal, study first author.

'The findings of this study open exciting new avenues for research into the cause of these conditions as well as developing new treatments for women suffering from them.'

The research was published in PLOS Biology.

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Healthy bone marrow may be important in fertility - BioNews

Actinium Announces Iomab-B Poster Selected for Honorable Distinction Award at the 2019 Society of Hematologic Oncology Annual Meeting from Nearly Four…

By adminSeptember 24, 2019Uncategorized

NEW YORK, Sept. 23, 2019 /PRNewswire/ --Actinium Pharmaceuticals, Inc., (NYSE AMERICAN: ATNM) ("Actinium") today announced that a poster highlighting Iomab-B, its pivotal Phase 3 targeted conditioning candidate, was awarded Honorable Distinction at the 2019 SOHO (Society of Hematologic Oncology) Annual Meeting. SOHO is the only international society specific to the field of hematologic oncology and has grown to over 3,000 members. This year's SOHO annual meeting was attended by nearly 1,400 physicians, nurses and healthcare professionals and nearly four hundred abstracts and posters were presented including over 70 focused on AML or acute myeloid leukemia.

Benjamin Tomlinson, M.D., Assistant Professor, Adult Hematologic and Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center (Cleveland, OH) and lead author of the poster, said, "It is an honor for our work to be recognized by SOHO's scientific committee from the significant number of posters and abstracts that were submitted. The AML therapeutic landscape has evolved rapidly in recent years with eight therapies gaining approval since 2017 including targeted agents like Bcl-2, FLT3 and IDH inhibitors. While these therapies are important advancements for patients with AML, they are not curative, and bone marrow transplant remains the only curative treatment option for patients with active relapsed or refractory AML. Iomab-B is highly differentiated as a targeted agent with a strong anti-leukemic effect as we have demonstrated in this poster selected by SOHO and targeted conditioning ability that led to all patients receiving Iomab-B achieving successful bone marrow transplant and engraftment. These findings are highly encouraging as I am not aware of any other agents that offer such a high probability of bone marrow transplant for this patient population. I look forward to continuing to participate in the SIERRA study and am excited for additional data in the future."

Mark Berger, M.D., Actinium's Chief Medical Officer, said, "This Honorable Distinction award from SOHO adds to the growing recognition for Iomab-B's value proposition as the only late-stage targeted conditioning agent for the older relapsed or refractory AML patient population. Since achieving twenty-five percent enrollment and making important changes to the trial protocol, including adding targeted therapies like venetoclax as options in the control arm and reducing the time to crossover evaluation to fourteen days, we have seen a dramatic increase in physician interest and enthusiasm for the SIERRA trial. This groundswell of interest continued to build after preliminary data from the first twenty-five percent of patients was presented in an oral presentation at the ASH annual meeting in 2018 and a late-breaking oral presentation at the TCT annual meeting in February 2019. These data demonstrated Iomab-B's ability to enable transplant universally, with deep donor chimerism and no non-relapse mortality at one hundred days post-transplant in the Iomab-B arm. Additionally, Iomab-B's ability as a single agent to rapidly deplete all circulating leukemic blasts prior to transplant has drawn strong recognition from the medical community, as evidenced by this award from SOHO. These data gained widespread visibility throughout the transplant and hematology communities and as a result, we have seen new sites come into the SIERRA trial bringing us to twenty sites in total at present. There has also been significant physician engagement, which drove us powerfully past fifty-percent enrollment. With the important fifty percent enrollment milestone achieved, we look forward to completing the SIERRA study and further demonstrating Iomab-B's value proposition at future medical meetings."

The poster presented at SOHO highlighted Iomab-B's ability as a single agent activity to rapidly deplete peripheral blasts leading to lower circulating leukemia tumor burden prior to BMT, which is critical for successful engraftment. It was observed that a single therapeutic infusion of Iomab-B resulted in a median reduction of peripheral blasts of 98% by day 3 and 100% reduction by day 8 following administration and prior to any other pre-BMT conditioning in the sixteen patients who were evaluated. Rapid reduction of peripheral blasts has been observed as an independent prognostic marker that is predictive of both CR or Complete Response and RFS or Relapse-Free Survival in patients with AML after receiving cytotoxic chemotherapy. Gianfaldoni et al1 performed an analysis of 30 newly diagnosed AML patients who were treated with cytotoxic induction chemotherapy and found that a rapid reduction of peripheral leukemia blasts correlated with responses and all patients that achieved CR had a rapid reduction of their peripheral blasts. Elliot et al2, performed a retrospective analysis of 86 adult patients with AML and identified time to clearance of circulating leukemia blasts as an independent prognostic marker of RFS that superseded all other known risk factors including karyotype and number of cycles of induction therapy needed to achieve CR. As previously presented, all patients receiving Iomab-B in the SIERRA trial, including cross over patients, received a BMT and achieved engraftment without delay.

The poster selected by SOHO for honorable distinction can be viewed on Actinium's website (here) or the SOHO Annual Meeting website (here).

About the Society of Hematologic OncologyThe Society of Hematologic Oncology (SOHO) is an international society designed specifically for clinicians, research scientists and related healthcare professionals who specialize in the research and treatment of patients with hematologic malignancies. SOHO's mission is to promote worldwide research and education through the exchange of scientific information. Organized by its founders and world class committees, SOHO is the only international society specific to this field. The 2019 SOHO Annual Meeting took place September 11-14 in Houston, Texas, with attendance from nearly 1,400 hematologic oncology professionals from across the globe. Nearly 400 abstracts were accepted for oral or poster presentation at the Annual Meeting. Published abstracts are available through the official journal of the Society, 'Clinical Lymphoma, Myeloma and Leukemia,' published by Elsevier. Online access is open to the public at https://www.clinical-lymphoma-myeloma-leukemia.com/issue/S2152-2650(19)X0009-9through December 31, 2019. For more information about the Society or to sign-up for FREE membership, go to the official website at https://www.sohoonline.org/.

About Iomab-B Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the anti-CD45 antibody apamistamab and the radioisotope iodine-131 that is intended to be a targeted conditioning agent prior to a BMT or bone marrow transplant. Iomab-B was developed at the Fred Hutchinson Cancer Research Center and has been studied in over 300 patients in multiple hematologic indications across 12 clinical trials in addition to the ongoing SIERRA study in older patients with active, relapsed or refractory AML or Acute Myeloid Leukemia prior to patients receiving an allogeneic BMT or bone marrow transplant. Iomab-B is Actinium's lead targeting conditioning ARC in its multi-target, multi-indication targeted conditioning pipeline that includes the Iomab-B and Actimab-MDS programs for BMT and the Iomab-ACT program that will study a lower dose of Iomab-B for lymphodepletion prior to CAR-T and other cellular therapies.

About Actinium Pharmaceuticals, Inc.Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT. Its Iomab-ACT or Adoptive Cell Therapy program targets CD45 and utilizes a lower dose of iodine-131 than Iomab-B or lutetium-177 and is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 100 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Sources:

1) Gianfaldoni et al. clearance of leukemic blasts from peripheral blood during standard induction treatment predicts the bone marrow response in acute myeloid leukemia: a pilot study. British Journal of Haematology, 2006 March 16; 134, 54-57.

2) Elliott et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood. 2007 Dec 15; 110(13):4172-4. Epub 2007 Oct 1.

Forward-Looking Statements for Actinium Pharmaceuticals, Inc. This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contact:

Actinium Pharmaceuticals, Inc. Actinium Pharmaceuticals, Inc.Steve O'LoughlinPrincipal Financial Officerinvestorrelations@actiniumpharma.com

Hans VitzthumLifeSci Advisors, LLCHans@LifeSciAdvisors.com(617) 535-7743

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Gene Therapy For Beta-Thalassemia: Updated Perspectives | TACG – Dove Medical Press

By adminSeptember 24, 2019Stem Cell Medicine

Garyfalia Karponi,1,* Nikolaos Zogas2,*

1Department of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece

*These authors contributed equally to this work

Correspondence: Garyfalia KarponiLaboratory of Microbiology and Infectious Diseases, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, GreeceTel +30 2310-999-956Fax +30 2310-999-934Email gkarponi@vet.auth.gr

Abstract: Allogeneic hematopoietic stem cell transplantation was until very recently, the only permanent curative option available for patients suffering from transfusion-dependent beta-thalassemia. Gene therapy, by autologous transplantation of genetically modified hematopoietic stem cells, currently represents a novel therapeutic promise, after many years of extensive preclinical research for the optimization of gene transfer protocols. Nowadays, clinical trials being held on a worldwide setting, have demonstrated that, by re-establishing effective hemoglobin production, patients may be rendered transfusion- and chelation-independent and evade the immunological complications that normally accompany allogeneic hematopoietic stem cell transplantation. The present review will offer a retrospective scope of the long way paved towards successful implementation of gene therapy for beta-thalassemia, and will pinpoint the latest strategies employed to increase globin expression that extend beyond the classic transgene addition perspective. A thorough search was performed using Pubmed in order to identify studies that provide a proof of principle on the aforementioned topic at a preclinical and clinical level. Inclusion criteria also regarded gene transfer technologies of the past two decades, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for beta-thalassemia. Overall, after decades of research, that included both successes and pitfalls, the path towards a permanent, donor-irrespective cure for beta-thalassemia patients is steadily becoming a realistic approach.

Keywords: gene therapy, gene editing, thalassemia, mobilization, viral vectors, clinical trials, hematopoietic stem cells

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Adipose Tissue-derived Stem Cells Market to Witness Comprehensive Growth by 2018 2028 – Commerce Gazette

By adminSeptember 24, 2019Stem Cell Medicine

Adipose tissue is rich in multi potent stem cells that have the capability to differentiate into a number of cell types including adipocytes, osteocytes, chondrocytes and others, in vitro. These Adipose Tissue-derived Stem Cells are used for a number of applications including stem cell differentiation studies, regenerative medicine, cell therapy, tissue engineering and development of induced pluripotent stem cell lineage. Adult stem cells such as the Adipose Tissue-derived Stem Cells have a very good potential for regenerative medicine. The Adipose Tissue-derived Stem Cells show higher yields compared with other stem cell sources. Some of the regenerative medicine applications using Adipose Tissue-derived Stem Cells include skin, bone and cartilage regeneration.

Although, Adipose Tissue-derived Stem Cells have the ability to differentiate into different cell types in vitro, unlike the embryonic stem cells they lack the ability to differentiate into all types of organs and tissues of the body. Derivation of stem cells from adipose tissue have a number of advantages including that fat tissue contain 100 to 1000 times more mesenchymal stem cells than the bone marrow. Furthermore the method of collection of fat tissue is relatively easier and is less invasive than that of bone marrow collection. Although Adipose Tissue-derived Stem Cells have a potential to be used in cell-based therapy, there are a number of challenges the Adipose Tissue-derived Stem Cells market has to face. Some of the challenge include the safety issue for the clinical use of Adipose Tissue-derived Stem Cells, development and differentiation of the cells, delivery of the cells in vivo and immune response after the transplant.

The global Adipose Tissue-derived Stem Cells market is segmented based on product type and end user. Based on product type the Adipose Tissue-derived Stem Cells can be categorized into cell line and reagent & kits. Cell line can be further classified based on the source of the adipose tissue such as human and rodents. Based on reagents the Adipose Tissue-derived Stem Cells market is further classified as media & sera and kits. Based on application the Adipose Tissue-derived Stem Cells market is classified into regenerative medicine, cell therapy, tissue engineering, and other applications such as cell differentiation studies and other similar research. End users of Adipose Tissue-derived Stem Cells market are biotechnology companies and academic and research institutes.

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The Global Adipose Tissue-derived Stem Cells market is classified on the basis of product type, end user and region:

Based on the Product Type, Adipose Tissue-derived Stem Cells market is segmented into following: Cell Line Human Adipose Tissue-derived Stem Cells Rat Adipose Tissue-derived Stem Cells Reagents & Kits Media & Sera Kits

Based on the application, Adipose Tissue-derived Stem Cells market is segmented into following: Regenerative medicine Tissue engineering Cell therapy Others

Based on the end user, Adipose Tissue-derived Stem Cells market is segment as below: Biotechnology companies Academic & Research Institutes

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Growing research activities using stem cells along with the growth of regenerative medicine and cell therapy the global Adipose Tissue-derived Stem Cells market is set to expand considerably during the forecast period. However, ethical concerns and stringent regulations may hinder the growth of the global Adipose Tissue-derived Stem Cells market.

On the basis of geography, global Adipose Tissue-derived Stem Cells market is segmented into six major regions that include North America, Latin America, Europe, Asia-Pacific excluding China, China and Middle East & Africa. North America is expected to be the most lucrative Adipose Tissue-derived Stem Cells market owing to increased research activity of stem cells. Furthermore government support for regenerative and stem cell based studies along with cell therapy studies is driving the growth of the Adipose Tissue-derived Stem Cells market in the region. Changing government regulations in china is supporting the research activity that supports the growth of the adipose tissue-derived stem cell market in the region at a considerable rate.

Key participants operating in the Adipose Tissue-derived Stem Cells market are: Lonza, ThermoFisher Scientific, Celprogen, Inc, American CryoStem, Rexgenero Ltd, iXCells Biotechnologies, Merck KGaA, Lifeline Cell Technology, and others.

The report covers exhaustive analysis on: Adipose Tissue-derived Stem Cells Market Segments Adipose Tissue-derived Stem Cells Market Dynamics Historical Actual Market Size, 2013 2017 Adipose Tissue-derived Stem Cells Market Size & Forecast 2018 to 2026 Adipose Tissue-derived Stem Cells market Current Trends/Issues/Challenges Competition & Companies involved Adipose Tissue-derived Stem Cells Market Drivers and Restraints

Regional analysis includes North America Latin America Europe Asia Pacific Excluding China China Middle East & Africa

Report Highlights: Shifting Industry dynamics In-depth market segmentation Historical, current and projected industry size recent industry trends Key Competition landscape Strategies for key players and product offerings Potential and niche segments/regions exhibiting promising growth A neutral perspective towards market performance

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Adipose Tissue-derived Stem Cells Market to Witness Comprehensive Growth by 2018 2028 - Commerce Gazette

Suntanner, Heal Thyself: Exosome Therapy May Enable Better Repair of Sun, Age-Damaged Skin – NC State News

By adminSeptember 24, 2019Stem Cell Medicine

In the future, you could be your very own fountain of youth or at least your own skin repair reservoir. In a proof-of-concept study, researchers from North Carolina State University have shown that exosomes harvested from human skin cells are more effective at repairing sun-damaged skin cells in mice than popular retinol or stem cell-based treatments currently in use. Additionally, the nanometer-sized exosomes can be delivered to the target cells via needle-free injections.

Exosomes are tiny sacs (30 150 nanometers across) that are excreted and taken up by cells. They can transfer DNA, RNA or proteins from cell to cell, affecting the function of the recipient cell. In the regenerative medicine field, exosomes are being tested as carriers of stem cell-based treatments for diseases ranging from heart disease to respiratory disorders.

Think of an exosome as an envelope with instructions inside like one cell mailing a letter to another cell and telling it what to do, says Ke Cheng, professor of molecular biomedical sciences at NCState, professor in the NCState/UNC-Chapel Hill Joint Department of Biomedical Engineering and corresponding author of a paper describing the work. In this case, the envelope contains microRNA, non-coding RNA that instructs the recipient cell to produce more collagen.

To test whether exosomes could be effective for skin repair, Cheng and his team first grew and harvested exosomes from skin cells. They used commercially available human dermal fibroblast cells, expanding them in a suspension culture that allowed the cells to adhere to one another, forming spheroids. The spheroids then excreted exosomes into the media.

These 3D structures generate more procollagen more potent exosomes than you get with 2D cell expansion, says Cheng.

In a photoaged, nude mouse model, Cheng tested the 3D spheroid-grown exosomes against three other treatments: retinoid cream; 2D-grown exosomes; and bone marrow derived mesenchymal stem cells (MSCs) exosomes, a popular stem cell-based anti-aging treatment currently in use. The team compared improvements in skin thickness and collagen production after treatment. They found that skin thickness in 3D exosome treated mice was 20% better than in the untreated and 5% better than in the MSC-treated mouse. Additionally, they found 30% more collagen production in skin treated with the 3D exosomes than in the MSC treated skin, which was the second most effective treatment.

I think this study shows the potential for 3D exosomes to be used in anti-aging skin treatments, says Cheng. There are two major benefits to exosome treatments over conventional treatments: one, you can use donor skin cells from anyone to grow and harvest these exosomes they arent cells, so you dont run the risk of rejection. And two, the treatment can be administered without needles exosomes are small enough to be able to penetrate the skin via pressure, or jet injection methods.

Our hope is that eventually people may be able to bank skin samples and come back to them, or use donor exosome treatments that they can administer themselves. We believe that this work is an important step toward potentiating future human clinical trials in the prevention and treatment of cutaneous aging.

The work appears in ACS Nano, and was sponsored in part by the National Institutes of Health and the American Heart Association. Postdoctoral researcher Shiqui Hu is first author.

-peake-

Note to editors: An abstract follows.

Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging

DOI: 10.1021/acsnano.9b04384

Authors: Shiqi Hu, Zhenhua Li, Jhon Cores, Ke Huang, Teng Su, Phuong-Uyen Dinh, Ke Cheng, North Carolina State University Molecular Biomedical Sciences Department and NCState/UNC-Chapel Hill Joint Department of Biomedical EngineeringPublished: Online in ACS Nano

Abstract: Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated in vitro and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-) and the upregulation of transforming growth factor beta (TGF-). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.

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Suntanner, Heal Thyself: Exosome Therapy May Enable Better Repair of Sun, Age-Damaged Skin - NC State News

Brain tumors form synapses with healthy neurons, Stanford-led study finds – Stanford Medical Center Report

By adminSeptember 24, 2019Stem Cell Medicine

Using optogenetic techniques, which relied on laser light to activate the cancer cells in mice implanted with human gliomas, the researchers demonstrated that increasing electrical signals into the tumors caused more tumor growth. Proliferation of the tumors was largely prevented when glioma cells expressed a gene that blocked transmission of the electrical signals.

Existing drugs that block electrical currents also reduced growth of high-grade gliomas, the research found. A seizure medication called perampanel, which blocks activity of neurotransmitter receptors on the receiving end of a synapse, reduced proliferation of pediatric gliomas implanted into mice by 50%. Meclofenamate, a drug that blocks the action of gap junctions, resulted in a similar decrease in tumor proliferation.

Monjes team plans to continue investigating whether blocking electrical signaling within tumors could help people with high-grade gliomas. Its a really hopeful new direction, and as a clinician Im quite excited about it, she said.

Other Stanford co-authors of the paper are staff scientist Wade Morishita, PhD; postdoctoral scholars Anna Geraghty, PhD, Marlene Arzt, MD, and Kathryn Taylor, PhD; graduate student Shawn Gillespie; medical student Lydia Tam; staff scientist Cedric Espenel, PhD; research assistants Anitha Ponnuswami, Lijun Ni and Pamelyn Woo; Hannes Vogel, MD, professor of pathology and of pediatrics; and Robert Malenka, MD, PhD, professor of psychiatry and behavioral sciences.

Monje is a member of Stanford Bio-X, the Stanford Institute for Stem Cell Biology and Regenerative Medicine, the Stanford Maternal & Child Health Research Institute, the Stanford Cancer Institute and the Wu Tsai Neurosciences Institute at Stanford.

Scientists from Massachusetts General Hospital, Harvard Medical School, the Massachusetts Institute of Technology, Johns Hopkins University, the University of Michigan and the University of California-San Francisco also contributed to the research.

The research was funded by the National Institutes of Health (grant DP1 NS111132), the National Institute of Neurological Disorders and Stroke (grant NINDS R01NS092597), the National Cancer Institute (grant F31CA200273), the Michael Mosier Defeat DIPG Foundation, the ChadTough Foundation, the V Foundation, Ians Friends Foundation, the Department of Defense, the Mckenna Claire Foundation, Alexs Lemonade Stand Foundation, The Cure Starts Now Foundation and DIPG Collaborative, the Lyla Nsouli Foundation, Unravel Pediatric Cancer, the California Institute for Regenerative Medicine, the Joey Fabus Childhood Cancer Foundation, the N8 Foundation, the Sam Jeffers Foundation, Cancer Research UK, the Virginia and D.K. Ludwig Fund for Cancer Research, and the Stanford Maternal & Child Health Research Institutes Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases.

Stanfords Department of Neurology and Neurological Sciences also supported the work.

A second paper showing similar findings by another team of researchers was published simultaneously in Nature.

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Brain tumors form synapses with healthy neurons, Stanford-led study finds - Stanford Medical Center Report

Stem Cell Assay Market Expected to Secure Notable Revenue Share During 2019-2027 – Commerce Gazette

By adminSeptember 24, 2019Stem Cell Medicine

Regenerative medicine has emerged as new paradigm in human health. It has the potential to resolve unmet medical needs. Rapid growth in the interdisciplinary field of regenerative medicine is altering the health care domain by converting fundamental science into a variety of regenerative technologies. Stem cell is an undifferentiated mass of cell that has the ability to divide indefinite times. It can be further differentiated into specialized cells such as blood cells, skin cells, neurons, heart cells, chondrocytes, and osteocytes under specific conditions. Unspecialized nature, self-renewal capability, and dedifferentiation are the unique features of stem cells. Thus, these cells are useful in different applications in pharmaceutical research and medical fields. Stem cell research has grown significantly since 1978, when stem cells were discovered in human cord blood. Incidence of cancer is increasing across the globe due to the rise in aging population and changing lifestyle habits. This, in turn, is boosting the demand for anticancer drugs and therapies. According to the Centers for Disease Control and Prevention, 14.1 million new cancer cases were diagnosed around the globe in 2012 and around 19.3 million new cancer cases are expected to be diagnosed each year by 2025. Rise in incidences of chronic diseases is boosting the demand for research, making stem cells a highly preferred system for drug discovery due to its self-renewal capability and unspecialized nature.

Over the last decade, the application of cell-based assays has increased at a rapid pace among research institutes and pharmaceutical industries. This was primarily ascribed to the ethical issues associated with the use of animals for clinical trials. Furthermore, rise in approvals of clinical trials for stem cells based therapy, increase in funds from government organizations, and technological advancements are some of the factors driving the stem cell assay market. But, human embryonic stem cells, which are derived from inner cell mass of blastocyst are currently high on the political issues ethical concerns in many countries hampering the growth of the market. Additionally, lack of required infrastructure in developing countries and high cost associated with products are some of the factors restraining the stem cell assay market. Evolution of new therapies and low regulatory frameworks in emerging regions are expected to provide opportunities for market growth during the forecast period.

The global stem cell assay market has been segmented based on product, assay type, application, end-user, and region. In terms of product, the market for stem cell assay has been divided into human embryonic stem cell kits and adult stem cell kits. The adult stem cell kits segment is further divided into induced pluripotent stem cells kits, hematopoietic stem cell kits, mesenchymal stem cell kits, umbilical cord stem cell kits, and others. The adult stem cell kits segment is expected to account for the prominent share of the global stem cell assay market during the forecast period, led by the rise in product innovation activities and increasing focus on drug screening by biotechnology and pharmaceutical industries. Based on assay, the global stem cell assay market has been segregated into viability or cytotoxicity assay, cell identification assay, proliferation assay, differentiation assay, apoptosis assay, isolation & purification assay, and functional assay. Among these, the viability or cytotoxicity assay segment is anticipated to constitute key share of the global stem cell assay market during the forecast period, as cytotoxicity is an unavoidable stage during research.

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In terms of application, the global stem cell assay market has been segmented into drug discovery & development, regenerative medicine & therapy development, and clinical research. The regenerative medicine & therapy development segment is anticipated to expand at a rapid pace during the forecast period due to the rise in incidence of Parkinsons, Alzheimers, diabetes, and cancer diseases. This is anticipated to augment the focus on the development of new therapies and innovative drugs. Evolution of new therapies is estimated to provide new opportunities for the growth of the stem cell assay market during the forecast period.

Based in end-user, the global stem cell assay market has been segregated into government research institutes, private research institutes, and industry research. The industry research segment is projected to account for the major share of the global stem cell assay market during the forecast period. Growth in adoption of stem cell assays for drug screening process and testing is likely to drive the segment in the near future.

In terms of geography, the global stem cell assay market has been divided into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America is expected to dominate the global stem cell assay market during the forecast period. Governmental initiatives for stem cell based research in North America are anticipated to boost the stem cell assay market in the region. The stem cell assay market in Asia Pacific is estimated to expand at a rapid pace; it is projected to overtake Europe in the near future. Development in the clinical research field and rise in patient pool are projected to augment the adoption of stem cell assay in Asia Pacific.

Key players operating in the stem cell assay market are Thermo Fisher Scientific,Merck KGaA, Promega Corporation, STEMCELL Technologies Inc., Bio-Techne Corporation, GE Healthcare, Cellular Dynamics International Inc., Hemogenix, Bio-Rad Laboratories, Inc., and Cell Biolabs Inc.

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The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

The study is a source of reliable data on: Market segments and sub-segments Market trends and dynamics Supply and demand Market size Current trends/opportunities/challenges Competitive landscape Technological breakthroughs Value chain and stakeholder analysis

The regional analysis covers: North America (U.S. and Canada) Latin America (Mexico, Brazil, Peru, Chile, and others) Western Europe (Germany, U.K., France, Spain, Italy, Nordic countries, Belgium, Netherlands, and Luxembourg) Eastern Europe (Poland and Russia) Asia Pacific (China, India, Japan, ASEAN, Australia, and New Zealand) Middle East and Africa (GCC, Southern Africa, and North Africa)

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

Highlights of the report: A complete backdrop analysis, which includes an assessment of the parent market Important changes in market dynamics Market segmentation up to the second or third level Historical, current, and projected size of the market from the standpoint of both value and volume Reporting and evaluation of recent industry developments Market shares and strategies of key players Emerging niche segments and regional markets An objective assessment of the trajectory of the market Recommendations to companies for strengthening their foothold in the market

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Stem Cell Assay Market Expected to Secure Notable Revenue Share During 2019-2027 - Commerce Gazette

Global Bio-Banks Market : Industry Analysis and Forecast (2017-2026) By Type, Product,Application,Analysis,and Region. – OnYourDesks

By adminSeptember 24, 2019Stem Cell Medicine

Global Bio-Banks Market was valued US$ 2.3 Bn in 2017 and is expected to reach US$ 6.7 Bn by 2026, at CAGR of 14.3% during forecast period.

Global Bio-Banks MarketAdvancement in biobanking operations in order to ensure optimization of sample storage and maintenance is one of the key factors driving this market. Regenerative medicine through stem cell technology is one of the important treatments for diseases, like Alzheimers, diabetes, cancers, and rare genetic diseases. In order to benefit from the existing therapies, umbilical cord cells and other stem cells are preserved. With the increase in awareness about stem cell therapies, there has been a larger number of parents who are choosing umbilical cord banks for their children. There are a number of donor banks that are coming up as well. Biobanks not only support in the therapies for genetic diseases but also in medical research on rare genetic disorders. Growing awareness about stem cell therapies and innovation in the field of regenerative medicine are driving the growth of the global biobank market.

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Growing in the incidence of chronic diseases, government initiatives, development in drug discovery, and innovation of regenerative medicines, increasing healthcare expenditure and improvement in the treatment of cell and tissue disorders are some of the key factors boosting the global biobanks market. Furthermore, increasing awareness about biobanks is projected to boost the market for biobanks. Rising demographics, economies, and growth in GDP in the emerging countries like India and China, technological advancement and new innovate techniques are expected to offer good opportunities in the global biobanks market. Green banking and virtual biobanks for energy efficiency are some of the key trends that have been observed in global biobanks market. At the same time, expensive techniques, lack of standardization, economic recession and ethical issues related are some of the major factors limiting the growth for global biobanks market.

According to various application, the biobank application is expected to hold a XX% share during the forecast period. On account of different biospecimens stored at biobanks are witnessing significant demand because to advancements in cell-based research activities. Growing demand from different end users has led to the establishment of a substantial number of population-based and disease-based banks in a few years. Population-based banks are established to support precision medicine research initiatives, whereas disease-specific biobanks provide resources to research communities to enable a better understanding of disease etiology.

Among the regions, North America presently leads the global market for biobanks, closely followed by Europe, and it is expected to expand further at the highest CAGR during the forecast period. The increasing demand for Bio-Banks in the U.S. and Canada has allowed the province to have the highest market share. The prominence of these regions on account of the increasing incidence of chronic diseases, the imperative need to find effective treatments for them, large amounts of government investments in the area of biobanks, and the growing number of research activities, together with drug discovery in the region.

The Bio-Banks market report contains in-depth analysis of major drivers, opportunities, challenges, industry trends and their impact on the market. The Bio-Banks market report also provides data about the company and its strategy. This report also provides information on the competitive landscape section of the report provides a clear insight into the market share analysis of key industry players. This research report also adds a snapshot of key competition, market trends during the forecast period, expected growth rates and the primary factors driving and impacting growth market data. This information will be beneficial or helpful to the decision makers.

The objective of the report is to present a comprehensive assessment of the market and contains thoughtful insights, facts, historical data, industry-validated market data and projections with a suitable set of assumptions and methodology. The report also helps in understanding the global Bio-Banks market dynamics, structure by identifying and analysing the market segments and project the global market size. Further, the report also focuses on the competitive analysis of key players by product, price, financial position, product portfolio, growth strategies, and regional presence. The report also provides PEST analysis, PORTERs analysis, and SWOT analysis to address questions of shareholders to prioritizing the efforts and investment in the near future to the emerging segment in the global Bio-Banks market.

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Scope of Global Bio-Banks Market:

Global Bio-Banks Market, ByType:

Optimized Pre-Formulated Media Non-Optimized, Isotonic Formulation MediaGlobal Bio-Banks Market, By Product:

Refrigerators Ice Machines Freezers LN2 Supply Tanks Alarm and Monitoring Systems Cryogenic Storage Systems AccessoriesGlobal Bio-Banks Market, By Application:

Biobanking Regenerative Medicine Drug DiscoveryGlobal Bio-Banks Market, By Analysis:

Human tissue and tumor cells Bio-fluids Stem cells Umbilical cordGlobal Bio-Banks Market, By Region:

North America Europe Asia-Pacific South America Middle East & AfricaKey Players Operated in Market Include:

Home-Brew media solutions Teva Pharmaceuticals Organ Recovery Systems Genzyme Thermofisher Scientific VWR International Beckman Coulter Inc. Taylor-Wharton Tecan AG Panasonic Biomedical Sales Europe B.V. Thermo Fisher Scientific Inc. Taylor-Wharton International LLC So-Low Environmental Equipment Co.

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MAJOR TOC OF THE REPORT

Chapter One: Bio-Banks Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Bio-Banks Market Competition, by Players

Chapter Four: Global Bio-Banks Market Size by Regions

Chapter Five: North America Bio-Banks Revenue by Countries

Chapter Six: Europe Bio-Banks Revenue by Countries

Chapter Seven: Asia-Pacific Bio-Banks Revenue by Countries

Chapter Eight: South America Bio-Banks Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Bio-Banks by Countries

Chapter Ten: Global Bio-Banks Market Segment by Type

Chapter Eleven: Global Bio-Banks Market Segment by Application

Chapter Twelve: Global Bio-Banks Market Size Forecast (2019-2026)

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Global Bio-Banks Market : Industry Analysis and Forecast (2017-2026) By Type, Product,Application,Analysis,and Region. - OnYourDesks

Translational Regenerative Medicine Market : 2024 Shares, Trend and Growth – Bee Tribune

By adminSeptember 24, 2019Stem Cell Medicine

Regenerative medicine is a segment of translational research in molecular biology and tissue engineering. It involves the process of regeneration of human cells, tissues, or organs to re-establish their normal functions through stimulation of bodys repair system. They are widely used in the treatment of many degenerative disorders occurring in the areas of dermatology, orthopedic, cardiovascular and neurodegenerative diseases. Stem cell therapy is the available tool in the field of translational regenerative medicine. It has gained importance in the past few years as it is a bio-based alternative to synthetic options. Stem cells have high power of regeneration. Hence, these enable production of other cells in the body. This has increased demand for stem cell therapy in the treatment of degenerative diseases. Currently, stem cell therapy has applications in the treatment of diseases such as autism, cancer, retinal diseases, heart failure, diabetes, rheumatoid arthritis, Alzheimers. Extensive research is being carried out on stem cell therapy. The Centre for Commercialization of Regenerative Medicine (CCRM) has reported around 1900 active clinical trials undergoing currently. It also reported 574 active industry-sponsored cell therapy clinical studies, 50 of these are in phase 3 development. Hence, stem cell therapy is projected to contribute to the growth of the translational regenerative medicine market. However, ethical issues in the use of embryonic stem cells is likely to restrain the market.

Rising prevalence of degenerative diseases, aging population, rapid growth of emerging countries, and technical advancements in developed countries are the major factors fueling the growth of the translational regenerative medicine market.

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The global translational regenerative medicine market has been segmented based on product type, therapy, application, and region. In terms of product type, the market has been categorized into cellular and acellular. The cellular segment dominated the global market in 2016. Based on therapy, the global translational regenerative market has been segmented into cell therapy, gene therapy, immunotherapy, and tissue engineering. Immunotherapy is projected to be the fastest growing segment during the forecast period. In terms of application, the market has been segmented into orthopedic & musculoskeletal, cardiology, diabetes, central nervous system diseases, dermatology, and others. Cardiology and orthopedic & musculoskeletal are anticipated to be the fastest growing segments of the global translational regenerative medicine market.In terms of region, the global translational regenerative medicine market has been segmented into North America, Latin America, Europe, Asia Pacific, and Middle East & Africa. North America dominated the global regenerative medicine market owing to a large number of leading companies and expansion of research and development activities in the U.S. Increased medical reimbursement and advanced health care also drive the market in the region. Orthopedic is the leading application segment contributing to the growth of the market in the region. Asia Pacific is forecasted the huge growth because of large consumer pool, rising income, and health care expenditure. However, the market in Asia Pacific could face challenges such as high cost of bio-based medicines and stringent regulatory policies.

The global translational regenerative medicine market is dominated by key players such as CONMED Corporation, Arthrex, Inc., Organogenesis, Inc., Nuvasive, Inc., Osiris Therapeutics, Inc., Celgene Corporation, Brainstorm Cell Therapeutics Inc. and Medtronic.

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Translational Regenerative Medicine Market : 2024 Shares, Trend and Growth - Bee Tribune