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The long and winding road of reprogramming-induced rejuvenation – Nature.com

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The long and winding road of reprogramming-induced rejuvenation - Nature.com

Looking for the Path to Safe Cell Rejuvenation – Lifespan.io News

By Induced Pluripotent Stem Cells

In Nature Communications, Ali Ycel and Vadim Gladyshev have published a review of the current state of the art in partial cellular reprogramming, detailing what this technology does and how it might be used safely.

This paper begins by treading familiar ground on the subject, explaining its end goals and purpose. When successful, partial cellular reprogramming induces reprogramming-induced rejuvenation (RIR), a state in which a cell is transformed into an epigenetically younger cell of the same type and fulfilling the same function [1]. This process has had multiple crucial successes in experimental models, including human muscle cells [2] and skin cells [3] along with restoring vision [4] and extending lifespan [5] in mice.

Much of this work has been done in mice that have been genetically modified to express the necessary factors when doxycycline is administered. This has even been accomplished after birth via an adeno-associated virus (AAV) [5]. While there are four Yamanaka factors, OSKM, the fourth, c-Myc, is often omitted because it raises the risk of cancer. OSK administration significantly reduced the frailty of the treated mice.

As the authors note, applying these sorts of genetic modification techniques directly to human beings is currently infeasible with existing technologies. Partial reprogramming requires carefully determined generation of Yamanaka factors inside cells. To apply this in a clinical setting would require gene therapy that has specific and strong effects on individual tissues, and using the AAV system that works on mice is not yet practical for people [6]. Generating partially reprogrammed cells outside the body, similarly to how induced pluripotent stem cells (iPSCs) are generated, may be feasible for therapeutic purposes.

Administering small molecules to people in order to effect rejuvenation in the form of a drug has been the dream of aging researchers for some time. Previous work has spurred the creation of iPSCs through such chemical means [7]. The authors of this review describe these methods as less powerful than gene therapy and requiring multiple stages of administration. This implies a degree of safety and control that makes them more attractive for human research.

An experiment on mouse cells, which also included Vadim Gladyshev, had revealed that using a 7c cocktail reduced multiple aspects of aging, including epigenetic clock measurements, age-related metabolic changes, and oxidative stress markers [8]. However, it also upregulates the senescence-associated p53 pathway, which is downregulated through normal reprogramming methods and may cause cells to become senescent earlier [9].

Normally, constant expression of the Yamanaka factors in a living organism causes its cells to completely revert to a pluripotent state, in which they forget their roles, become cancerous, and cause the organism to die. For example, inducing OSKM for six days in the hearts of mice was found to be beneficial for them, while extending it for a dozen days proved lethal [10]. However, constantly inducing OSK in neural ganglion cells for a full 10-18 months improved vision without this side effect [4].

The authors note many of the aspects of aging that are improved or possibly improved with RIR, of which the most obvious, epigenetic alterations, is only one. Inflammation and proteostasis are also affected. Telomere attrition, however, occurs only in later reprogramming and is not affected by the partial variety [11]. Direct changes to cellular communication and genomic stability are not yet known.

However, the authors point out that, while full reprogramming does not cells to mutate, creating colonies of iPSCs causes evolutionary pressure: cells with mutations that may not be beneficial for the whole organism may be more prevalent in iPSC colonies [12]. It remains to be seen if this is a concern for partial reprogramming.

The authors also mention a biochemical pluripotency network and the fundamental differences between full and partial rejuvenation. Most critically, they hold that partial reprogramming is caused by factors that are downstream of full reprogramming. If it is possible to directly affect these factors instead of relying on the Yamanaka full-reprogramming factors, it might be possible to cause RIR without risking the dangerous side effects associated with complete reprogramming. However, this area of research remains unexplored.

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[1] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.

[2] Sarkar, T. J., Quarta, M., Mukherjee, S., Colville, A., Paine, P., Doan, L., & Sebastiano, V. (2020). Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells. Nature communications, 11(1), 1545.

[3] Gill, D., Parry, A., Santos, F., Okkenhaug, H., Todd, C. D., Hernando-Herraez, I., & Reik, W. (2022). Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. Elife, 11, e71624.

[4] Lu, Y., Brommer, B., Tian, X., Krishnan, A., Meer, M., Wang, C., & Sinclair, D. A. (2020). Reprogramming to recover youthful epigenetic information and restore vision. Nature, 588(7836), 124-129.

[5] Macip, C. C., Hasan, R., Hoznek, V., Kim, J., Lu, Y. R., Metzger IV, L. E., & Davidsohn, N. (2024). Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice. Cellular Reprogramming, 26(1), 24-32.

[6] Pupo, A., Fernndez, A., Low, S. H., Franois, A., Surez-Amarn, L., & Samulski, R. J. (2022). AAV vectors: The Rubiks cube of human gene therapy. Molecular Therapy.

[7] Guan, J., Wang, G., Wang, J., Zhang, Z., Fu, Y., Cheng, L., & Deng, H. (2022). Chemical reprogramming of human somatic cells to pluripotent stem cells. Nature, 605(7909), 325-331.

[8] Mitchell, W., Goeminne, L. J., Tyshkovskiy, A., Zhang, S., Chen, J. Y., Paulo, J. A., & Gladyshev, V. N. (2023). Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation. bioRxiv, 2023-06.

[9] Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., & Donehower, L. A. (2002). p53 mutant mice that display early ageing-associated phenotypes. Nature, 415(6867), 45-53.

[10] Chen, Y., Lttmann, F. F., Schoger, E., Schler, H. R., Zelarayn, L. C., Kim, K. P., & Braun, T. (2021). Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice. Science, 373(6562), 1537-1540.

[11] Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell, 126(4), 663-676.

[12] Kosanke, M., Osetek, K., Haase, A., Wiehlmann, L., Davenport, C., Schwarzer, A., & Martin, U. (2021). Reprogramming enriches for somatic cell clones with small-scale mutations in cancer-associated genes. Molecular Therapy, 29(8), 2535-2553.

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Looking for the Path to Safe Cell Rejuvenation - Lifespan.io News

Company Trying to Resurrect a Mammoth Makes a Stem Cell Breakthrough – Gizmodo

By Induced Pluripotent Stem Cells

Colossal Biosciences, which calls itself the worlds first de-extinction company, has created stem cells it thinks will hasten the companys marquee goal of resurrecting the woolly mammoth. The teams research describing the accomplishment will be hosted on the preprint server bioRxiv.

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The cells are induced pluripotent stem cells (iPSC), a type of cell that can be reprogrammed to develop into any other type of cell. The cells are especially useful in bioengineering, for their applications in cell development, therapy, and transferring genetic information across species. Colossals new iPSCs are the first engineered elephant cells converted into an embryonic state, a useful development if youre in pursuit of a woolly mammoth. Or rather, an animal that looks like a woolly mammoth.

In the past, a multitude of attempts to generate elephant iPSCs have not been fruitful. Elephants are a very special species and we have only just begun to scratch the surface of their fundamental biology, said Eriona Hysolli, who heads up Colossals biological sciences team, in a statement. The Colossal mammoth team persisted quite successfully as this progress is invaluable for the future of elephant assisted reproductive technologies as well as advanced cellular modeling of mammoth phenotypes.

According to the Colossal release, the new stem cells were able to differentiate into the three germ layers that result in every cell type. It opens the door to establishing connections between genes and traits for both modern and extinct relativesincluding resistance to environmental extremes and pathogens, said George Church, a geneticist and co-founder of Colossal, in a press release.

The animals Colossal hopes to produce will be Asian elephants (E. maximus), genetically engineered to be resistant to the cold and, most notably, covered in shaggy hair la woolly mammoth, their extinct cousin. Colossal also has plans to produce approximate (or proxy) species of the Tasmanian tiger or thylacine, which went extinct around 1936, and the dodo, a flightless bird native to Mauritius, which was gone by 1681. Other companiesnamely Revive & Restorehave similar aims with other species, including the heath hen and passenger pigeon.

A proxy species isnt truly the old creature brought back to life. As described in a 2016 report by the International Union for Conservation of Natures Species Survival Commission, Proxy is used here to mean a substitute that would represent in some sense (e.g. phenotypically, behaviourally, ecologically) another entity the extinct form. The group added that Proxy is preferred to facsimile, which implies creation of an exact copy.

One expert who spoke to Gizmodo previously referred to the end-goals of these companies as something out of Lovecraft and the elephantine effort as a simulacrum that has no phylogenetic relationship with actual mammoths.

Its not just a question of having biological material from an extinct animal. Researchers exploring the possibility of resurrecting the Christmas Island rat found that some genetics were simply lost to time, in spite of the amount that could be gleaned from historic tissues and its nearest extant relatives. One member of the team told Gizmodo that We arent actually planning to do it, as probably the world doesnt need any more rats, and probably the money it would take to do the best job possible could be spent on better things, e.g., conserving living things. (That researcher is now a member of Colossals advisory board.) Nevertheless, the production of elephant iPSCs is a step toward producing these proxy animals, an aim that many scientists see as likely but fewer see as useful.

Once Colossal produces a herd of proxy mammoths, its intention is to decelerate the melting of the permafrost by loosing the animals on a swath of Siberia. Ultimately, Colossal says, the mammoth steppethe ancient ecosystem in which the giant proboscideans roamedcould be restored, helping fight climate change and pushing new technologies in gene editing in the process, helping extant elephants, which face their own survival threats.

But other technological breakthroughs will be necessary to make any of that possible. As noted by Nature, Church intends to use artificial elephant wombs to produce the proxy mammoths, so as to not require Asian elephant surrogates. Asian elephants are an endangered species; to use them as surrogates for proxy mammoths would be the cherry-on-top of an ethical dilemma sundae.

Were still a long way off from Colossals ultimate goals, but this recent achievement is a significant one, and a reminder that these de-extinction efforts involve serious science.

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Company Trying to Resurrect a Mammoth Makes a Stem Cell Breakthrough - Gizmodo

Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration – Nature.com

By Induced Pluripotent Stem Cells

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Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration - Nature.com

Vampire Breast Lift 101: Everything to Know About the Trending Treatment – NewBeauty Magazine

By Platelet Rich Plasma Injections

By now you must have heard of the Vampire Facial which was first popularized in 2013 when Kim Kardashian took a now infamous bloody selfie. Just like the Vampire Facial, the Vampire Breast Lift utilizes platelet-rich plasma (PRP) derived from a persons own blood. The Vampire Breast Lift involves injections of PRP in the breasts to enhance fullness and lift for a quick cleavage boost.

Developed by Fairhope, AL, dermatologist Charles Runels, MD, the procedure involves drawing blood, isolating platelets containing growth factors, and combining them with hyaluronic acid fillers. Injecting this cocktail directly into the breasts can address concerns like inverted nipples, sagging, stretch marks and lack of perkiness.

Huntington Beach, CA, plastic surgeonPeter Newen, MD says that PRP injections may improve skin quality, but dont expect a lift. PRP injections may achieve some skin improvement but claims such as increased fatty tissue volume and lifting will not be observable, says Dr. Newen.

Although patients may see a temporary improvement, the results do not compare to a traditional breast lift. This should not be compared with a surgical breast lift or augmentation, in which there is a clear, long-lasting improvement.Adding PRP to the breasts can improve theskin, but it wont make a noticeable difference in breast volume or perkiness, he adds.

Dr. Runels claims that the effects of the Vampire Breast Lift may last one to two years, although these assertions lack independent verification. Grand Rapids, MI, plastic surgeonBradley Bengtson, MDexpresses concerns about the lack of data and clinical studies supporting the procedures safety and efficacy. Candidates for the Vampire Breast Lift should consult with a qualified medical professional to assess suitability and potential risks. The concerns I have with this procedureare that it tends to be performed by non-core physicians and nonsurgical doctors. There is absolutely no data about it yet, nor have there been any studies or findings on either the benefits or clinical risks associated with it, says Dr. Bengtson.

The procedure, which reportedly takes just 15 minutes, typically ranges in cost from $1,500 to $2,000. However, the exact price may vary depending on factors such as practice location and the expertise of the administering physician.

There are minimal risks, including potential bruising and swelling that typically resolve within a few days. It is essential for individuals considering this treatment to consult with board-certified providers.

While the procedure is generally deemed safe, Dr. Bengtson highlights the lack of conclusive evidence regarding long-term safety, particularly in relation to its potential impact on breast health. The breast is a cancer-prone organ, and with one in eight women in the U.S. developing breast cancer, you must wonder, what effect do these injections have on an established cancer? We dont have an answer to that yet, he cautions.

As of now, there is no FDA approval specifically for this procedure. Patients considering this treatment should thoroughly discuss potential side effects and concerns with their healthcare provider before proceeding.

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Vampire Breast Lift 101: Everything to Know About the Trending Treatment - NewBeauty Magazine

Stem Cells. Let’s get things straight about what they are, and what they are not. Ethically and legally Sonoran News – Sonoran News

By Embryonic Stem Cells

Once again, I receive so many emails regarding stem cells, and where they come from. This is the biggest topic of questions I receive each week. The first thing Id like to say is that in my office, Accurate Care Medical Wellness Center, only ethical and legal sources of stem cells are used. We also use cells and protocols that are the most effective for each condition a patient may have. I personally go to three stem cell conferences a year to stay current with all of the products and protocols that are available.

It seems that people have been told about what used to be done back when stem cell therapy started. Very little information is available to the public that explains the recent technology and sources of stem cells and their ability to restore function to otherwise dysfunctional systems of the body to promote healing. I will do my best to shed light on this subject, while clarifying what they are and what they are not.

Lets start with what stem cells we do not use in my office. Embryonic stem cells are derived from embryos that are typically created through in vitro fertilization (IVF) procedures for reproductive purposes. These unused embryos are typically donated for research purposes with the informed consent of the donors. In some cases, aborted embryos may be used. In 2001, then-President George W. Bush announced a policy limiting federal funding for research involving embryonic stem cells. This policy allowed federal funding only for research on embryonic stem cell lines that had already been established before August 9, 2001. In 2009, President Barack Obama issued an executive order that lifted the restrictions on federal funding for embryonic stem cell research. This allowed for the funding of research on new embryonic stem cell lines. We do not use embryonic stem cells for treatments in my office, as we do not use products that are illegal, unethical or controversial.

Amniotic stem cells are derived from the amniotic fluid and amniotic membrane surrounding the fetus during pregnancy, generally obtained through procedures like amniocentesis, the umbilical cord (in stem cell therapy for labs), or during a cesarean section childbirth. Unlike embryonic stem cells, which are derived from embryos, amniotic stem cells are obtained without harming the fetus and are ethically uncontroversial. We use MSCs or Mesenchymal Stem Cells, and extra cellular cells or exosomes in my office.

We use stem cells, now known as HCT or Human Cellular Tissue Therapy. This term is now used, as not all products used for treatments today contain stem cells, Some are extracellular products. Extracellular vesicles (EVs)derived from mesenchymal stem cells, (MSCs) play a critical role in the development of immune regulation and regeneration. These mimic the effects of stem cells and perform powerful functions. In my office, each patient, case and condition is unique, therefore different products and protocols are used for each and every patient. As work continues, researchers are actively developing engineered EVs that are even more effective.

Many patients tell me that theyve previously received the following types of stem cells when they received stem cell therapy that did not work prior to coming to my office.

Two of the popular forms of stem cell therapy theyve received are adipose (fat) and bone marrow derived cells. These two sources of stem cells can work well for younger patients. The challenge that arises with older patients, especially those over the age of 60, is that these cells come from an older body.

Many of the regenerative properties of the cells have been used up and overworked over the years. This leaves the patient with compromised cells that are not going to regrow the tissue in question to the level and expectations the patient and doctor are willing to see. The two forms of stem cell extraction from the patient are invasive, and can be quite painful, especially those from bone marrow. Using stem cells, and extracellular cells from the donated umbilical cord of live birth of a baby is much less invasive for the donor (baby) and the recipient (patient).

For any questions regarding regenerative medicine, and whether it may help you, please call my office for a complimentary consultation. I offer special discounts for my readers as well. We frequently offer evening lectures in my office to learn more about regenerative medicine. If you would like to be added to our list for future events, please call my office.

For questions regarding any of my articles, please email me at [emailprotected] Leisa-Marie Grgula. DC Chiropractic Physician Accurate Care Medical Wellness Center 18261 N. Pima Rd. Ste. #115 Scottsdale, AZ 85255 480-584-3955

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Stem Cells. Let's get things straight about what they are, and what they are not. Ethically and legally Sonoran News - Sonoran News

Distinct pathways drive anterior hypoblast specification in the implanting human embryo – Nature.com

By Embryonic Stem Cells

Ethics statement

Human embryo work was regulated by the Human Fertility and Embryology Authority under licence R0193. Approval was obtained from the Human Biology Research Ethics Committee at the University of Cambridge (reference HBREC.2021.26). All work is compliant with the 2021 International Society for Stem Cell Research (ISSCR) guidelines. Patients undergoing IVF at CARE Fertility, Bourn Hall Fertility Clinic, Herts & Essex Fertility Clinic, and Kings Fertility were given the option of continued storage, disposal or donation of embryos to research (including research project specific information) or training at the end of their treatment. Patients were offered counselling, received no financial benefit and could withdraw their participation at any time until the embryo had been used for research. Research consent for donated embryos was obtained from both gamete providers. Embryos were not cultured beyond day 14 post-fertilization or the appearance of the primitive streak. Human stem cell work was approved by the UK Stem Cell Bank Steering Committee (under approval SCSC21-38) and adheres to the regulations of the UK Code of Practice for the Use of Human Stem Cell Lines. Mice were kept in an animal house in individually ventilated housing on 12:12h lightdark cycle with ad libitum access to food and water. Ambient temperature was maintained at 2122C and humidity at 50%. Experiments with mice are regulated by the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 and carried out following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body. Experiments were approved by the Home Office under licences 70/8864 and PP3370287. CD1 wild-type males aged 645weeks and CD1 wild-type females aged 618weeks were used for this study. Animals were inspected daily, and those showing health concerns were culled by cervical dislocation.

Raw fastq files from human datasets26,27,36,45, cynomolgus monkey datasets28,35 and mouse datasets68,69,70,71 were obtained from public repositories with wget. All human datasets were aligned to the GRCh38 reference using kb-pythons kb ref function to generate a reference. For cynomolgus monkey, National Center for Biotechnology Information (NCBI) genome build 5.0 transcriptome fasta files were adjusted to Ensembl style and used in kb ref to generate a custom index. For the mouse, GRCm39 reference was used with kb ref to generate a custom index. All datasets were re-aligned using either kb-python or kallisto72,73, after data handling as below. Human datasets: 10x v2 data from Mol et al. were processed as previously described10. For Zhou et al.27, read1 files were trimmed using cutadapt74 for the reported adapter sequence. Trimmed reads were then aligned using the kb-python kb count function with custom specifications (-x 1,0,8:1,8,16:0,0,0) and the custom barcode whitelist available. Each pair of fastqs was processed individually into barcodegene matrices and concatenated. For Xiang et al.26, a batch file was generated with cell ID, read1 and read2 for each fastq pair listed. Kallistos pseudo quant command was then used to generate a cell IDgene matrix. For Blakely et al.36, reads were aligned using kallisto pseudo quant. For Petropoulos et al.45, single-end reads were processed with kallisto pseudo quant with a pre-made batch file as above with 43 base pair read length specified. Cynomolgus datasets: for Ma et al.28, read1 fastqs were trimmed using cutadapt for TSO and polyA tail as described in the original publication. Next, kb pythons kb count function was used with custom specifications (x 1,0,8:1,8,16:0,0,0). For Yang et al.35, reads were aligned using kb pythons kb count command with 10xv3 technology specified. For Nakamura et al.21, available count tables were used given the use of SOLiD sequencer limiting re-alignment program options. Mouse datasets: for Mohammed et al.70, kallisto pseudo quant with a generated batch file was used to generate a cell IDgene matrix. For Deng et al.69 and Cheng et al.68, single-end reads were aligned with kallisto pseudo quant. Finally, for Pijuan-Sala et al.71, each sample set of 33 fastq files was aligned with kb count, with 10xv1 technology specified. The resulting set of barcodegene matrices was then concatenated for downstream analysis.

Following re-alignment, any datasets not generated using unique molecular identifier counts were normalized using quminorm75. First, matrices were converted to transcripts per kilobase million (TPM), and then the TPM matrix ran through quminorm with a shape parameter up to a maximum of 2 that did not create not available/applicable (NA) values in the matrix. Then, each individual dataset was made into a Seurat object76. Each individual dataset was then merged into a species-specific Seurat object, with SCT batch correction applied across datasets. Clusters were identified on the basis of canonical marker expression. To perform module scoring, gene lists were obtained from rWikiPathways77. For the monkey and mouse, gene symbols were converted to human homologues using bioMart78. Seurats AddModuleScore function was used with WikiPathway gene lists of interests as input. For CellPhoneDB analysis41, human data were split on the basis of stage, and subset matrix and metadata for cell type were output as txt files. CellPhoneDB was then run with respective files and counts-data set to gene_name. Data visualization was performed using Seurats DimPlot, FeaturePlot and VlnPlot functions, Scillus (https://scillus.netlify.app) Plot_Measure function, pheatmap and CellPhoneDBs dotplot function.

The scripts used for analyses are available at ref. 79.

Human embryos were thawed and cultured as described previously10,24. Briefly, cryopreserved human blastocysts (day 5 or 6) were thawed using the Kitazato thaw kit (VT8202-2, Hunter Scientific) according to the manufacturers instructions. The day before thawing, TS solution was placed at 37C overnight. The next day, IVF straws were submerged in 1ml pre-warmed TS for 1min. Embryos were then transferred to DS for 3min, WS1 for 5min and WS2 for 1min. These steps were performed in reproplates (REPROPLATE, Hunter Scientific) using a STRIPPER micropipette (Origio). Embryos were incubated at 37C and 5% CO2 in normoxia and in pre-equilibrated human IVC1 supplemented with 50ngml1 insulin growth factor-1 (IGF1) (78078, STEMCELL Technologies) under mineral oil for 14h to allow for recovery. Following thaw, blastocysts were briefly treated with acidic Tyrodes solution (T1788, Sigma) to remove the zona pellucida and placed in pre-equilibrated human IVC1 in eight-well -slide tissue culture plates (80826, Ibidi) in approximately 400l volume per embryo per well. Half medium changes were done every 24h. For small-molecule experiments, human IVC1 was supplemented with either 2M A83-01 (72022, STEMCELL Technologies)80,81, 25ngml1 Activin-A (Qk001, QKINE)82,83,84, 200nM LDN (S2618, SelleckChem)85,86, 50ngml1 BMP6 (SRP3017, Sigma Aldrich)85,86, 20M DAPT (72082, STEMCELL Technologies)87,88,89,90, 10M Compound-E (ab142164, Abcam)91,92,93, 20M MK-0752 (S2660, Selleck Chemicals)94,95,96 or dimethyl sulfoxide (DMSO) for 48h. In all cases, these concentrations fall within a range of those used for either vertebrate embryos or complex human ES cell-derived models of the embryo. Within these ranges, a low-to-intermediate concentration was selected to avoid non-specific cytotoxic effects while still considering the higher concentration needed for embryo permeation compared with minimal 2D cell culture to achieve inhibitor action. Further, all small molecules and proteins were tested on human ES cells to validate the efficacy and test for cytotoxicity. For analysis, embryos were fixed in 4% paraformaldehyde for 20min at room temperature for downstream analysis.

Pregnant, time-staged mice were culled by cervical dislocation, and uteri were dissected and placed in M2 medium (pre-warmed if embryos were for in vitro culture, ice cold if for fixing). E3.5 blastocysts were flushed out of uteri of pregnant females and either fixed for immunofluorescence analysis or transferred to acidic Tyrodes solution for zona pellucida removal. Embryos were cultured for 48h in CMRL (11530037, Thermo Fisher Scientific) supplemented with 1 B27 (17504001, Thermo Fisher Scientific), 1 N2 (made in-house), 1 penicillinstreptomycin (15140122, Thermo Fisher Scientific), 1 GlutaMAX (35050-038, Thermo Fisher Scientific), 1 sodium pyruvate (11360039, Thermo Fisher Scientific), 1 essential amino acids (11130-036, Thermo Fisher Scientific), 1 non-essential amino acids (11140-035, Thermo Fisher Scientific) and 1.8mM glucose (G8644, Sigma) supplemented with 20% foetal bovine serum5,28. Embryos were incubated with 25ngml1 Activin-A, 200nM LDN, 50ngml1 BMP6, 20M DAPT or DMSO for 48h. For E4.5, E5.5 and E5.75 collections, embryos were dissected directly from the uteri and fixed for analysis. For E5.0 collection, embryos were dissected from the uteri, and Reicherts membrane was removed before culturing or 36h with relevant small molecules as described above.

Shef6 human ES cells (R-05-031, UK Stem Cell Bank) were routinely cultured on 1.6% v/v Matrigel (354230, Corning) in mTeSR1 medium (85850, STEMCELL Technologies) at 37C and 5% CO2. Cells were passaged every 35days with TrypLE Express Enzyme (12604-021, Thermo Fisher Scientific). The ROCK inhibitor Y-27632 (72304, STEMCELL Technologies) was added for 24h after passaging. Cells were routinely tested for mycoplasma contamination by polymerase chain reaction. To convert primed human ES cells to RSeT or PXGL naive conditions, cells were passaged onto mitomycin-C inactivated CF-1 MEFs (3103 cellscm2; GSC-6101G, Amsbio) in human ES cell medium containing Dulbeccos modified Eagle medium (DMEM)/F12 supplemented with 20% Knockout Serum Replacement (10828010, Thermo Fisher Scientific), 100M -mercaptoethanol (31350-010, Thermo Fisher Scientific), 1 GlutaMAX (35050061, Thermo Fisher Scientific), 1 non-essential amino acids, 1 penicillinstreptomycin and 10ngml1 FGF2 (University of Cambridge, Department of Biochemistry) and 10M ROCK inhibitor Y-27632 (72304, STEMCELL Technologies). For RSeT conversion, cells were switched to RSeT medium (05978, STEMCELL Technologies). Cells were maintained in RSeT and passaged as above every 46days. For PXGL conversion, previously described protocols were used97. Briefly, cells were cultured in hypoxia and medium was switched to chemically Resetting Media 1 (cRM-1), which consists of N2B27 supplemented with 1M PD0325901 (University of Cambridge, Stem Cell Institute), 10ngml1 human recombinant LIF (300-05, PeproTech) and 1mM valproic acid. N2B27 contains 1:1 DMEM/F12 and Neurobasal A (10888-0222, Thermo Fisher Scientific) supplemented with 0.5 B27 (10889-038, Thermo Fisher Scientific) and 0.5 N2 (made in-house), 100M -mercaptoethanol, 1 GlutaMAX and 1 penicillinstreptomycin. cRM-1 was changed every 48h for 4days. Subsequently, medium was changed to PXGLN2B27 supplemented with 1M PD0325901, 10ngml1 human recombinant LIF, 2M G6983 (2285, Tocris) and 2M XAV939 (X3004, Merck). PXGL cells were passaged every 46days using TrypLE (12604013, Thermo Fisher Scientific) for 3min, and 10M ROCK inhibitor Y-27632 and 1lcm2 Geltrex (A1413201, Thermo Fisher Scientific) were added at passage for 24h.

For small-molecule experiments, primed or PXGL human ES cells were plated into ibiTreat dishes at normal passage densities. Forty-eight hours after passage, medium was changed to N2B27 supplemented with 25ngml1 Activin-A, 2M A83-01, 50ngml1 BMP6, 200nM LDN or 20M DAPT. Plates were then fixed for 20min in 4% paraformaldehyde for downstream analysis. For 3D culture of primed human ES cells, 30,000 cells were resuspended in 200l of ice-cold Geltrex and the resulting mix was plated into a single well of an 8 -well ibiTreat dish. Geltrex was polymerized by placement at 37C for 10min. Two-hundred microlitres of mTeSR1 with ROCK inhibitor Y-27632 was added after polymerization. Twenty-four hours later, the medium was changed to N2B27 (10M DAPT). Medium was refreshed 24h later, and the plate was fixed in 4% paraformaldehyde for 30min after a total of 48h in experimental conditions. Conditioned medium experiments were performed as described previously48. Briefly, 80l of ice-cold Geltrex was added to an 8 -well ibiTreat dish to create a 100% Geltrex bed. This was polymerized at 37C for 4min. A total of 1103 cellscm2 primed human ES cells were then added onto this bed in DMEM/F12 and allowed to settle for 15min. After this, medium was carefully switched to conditioned medium (described below) with 5% Geltrex (v/v) and 10M ROCK inhibitor Y-27632. Conditioned medium with 5% Geltrex was refreshed daily for the next 2days, and the resulting spheroids were fixed after a total of 72h.

YSLC differentiation was carried out as published48. Briefly, Shef6 human ES cells cultured in RSeT medium for at least 2weeks were plated onto ibiTreat dishes at 1103 cellscm2 in RSeT medium with 10M Y-27632. Medium was changed the next day to ACL differentiation medium consisting of N2B27 supplemented with 5% v/v Knockout Serum Replacement, 100ngml1 Activin-A, 3M CHIR99021 (University of Cambridge Stem Cell Institute) and 10ngml1 human recombinant LIF. Medium was refreshed every 48h, and 2M A83-01, 200nM LDN or 20M DAPT was added to ACL medium for 48h from either day 2 to day 4, followed by fixation, or day 4 to day 6 followed by fixation. For conditioned medium experiments, at day 6 cells were washed three times with phosphate-buffered saline and then mTeSR Plus medium (100-0276; STEMCELL Technologies) was added for 24h. Medium was collected from YSLCs and passed through a 0.45-m filter (16555, Sartorious), and stored for up to 1week at 4C.

CD1 mouse ES cells (generous gift from Prof. Jennifer Nichols (Stem Cell Institute, University of Cambridge, UK)) were routinely cultured on gelatin-coated (G7765, Sigma Aldrich) dishes in N2B27 supplemented with 1m PD0325901, 3m CHIR99021 and 10ngml1 mouse Lif (University of Cambridge, Stem Cell Institute). Medium was changed every 48h, and cells were passaged every 35days using trypsinethylenediaminetetraacetic acid (25300062; Life Technologies). For experiments, cells were passaged as normal into ibiTreat dishes. The following day, medium was switched to either N2B27+2iLif, N2B27, or N2B27+200nM LDN. Medium was refreshed after 24h, and cells were fixed after 48h.

Embryos were fixed in 4% paraformaldehyde, permeabilized in 0.1M glycine with 0.3% Triton X-100 and placed in blocking buffer containing 1% bovine serum albumin and 10% foetal bovine serum. Primary antibodies were diluted in blocking buffer and added overnight at 4C. Fluorescently tagged secondary antibodies were added for 2h at room temperature. Primary antibodies used in this study are as follows: mouse monoclonal anti OCT3/4 (sc5279, Santa Cruz; 1:200 dilution), rat monoclonal anti SOX2 (14-19811-82, Thermo Fisher Scientific; 1:500 dilution), goat polyclonal anti NANOG (AF1997 R&D Systems; 1:500 dilution), rabbit monoclonal anti GATA6 (5851, Cell Signaling Technology; 1:2,000 dilution), goat polyclonal anti GATA6 (AF1700, R&D Systems; 1:200 dilution), mouse anti monoclonal Cdx2 (MU392-UC, Biogenex; 1:200 dilution), goat polyclonal anti CER1 (AF1075, R&D Systems; 1:250 dilution), rat monoclonal anti Cerebus1 (MAB1986, R&D Systems; 1:200 dilution), rabbit monoclonal anti Phospho-Smad1(Ser463/465)/Smad5(Ser463/465)/Smad9(Ser465/467) (13820T, Cell Signaling Technology; 1:200 dilution), rabbit monoclonal anti Smad2.3 (8685T, Cell Signaling Technology; 1:200 dilution), rabbit monoclonal anti-cleaved caspase 3 (9664, Cell Signaling Technology; 1:200 dilution), mouse monoclonal anti Podocalyxin (MAB1658, R&D Systems; 1:500 dilution), goat polyclonal anti Brachyury (AF2085, R&D Systems; 1:500 dilution), rat monoclonal anti GATA4 (14-9980-82, Thermo Fisher Scientific; 1:500 dilution), goat polyclonal anti AP2-gamma (AF5059, R&D Systems; 1:500 dilution), goat polyclonal anti Otx2 (AF1979, R&D Systems; 1:1,000 dilution) and Alexa Flour 594 Phalloidin (A12381, Thermo Fisher Scientific; 1:500 dilution).

Immunofluorescence images were captured on a Leica SP8 confocal and processed and analysed using Fiji (http://fiji.sc). Epiblast, hypoblast and CER1-positive cell numbers were manually counted using the multi-point cell counter plugin. Quantification of trophectoderm was performed using Imaris software (version 9.1.2) using the spots tool with manual curation. To quantify n/c SMAD2.3 in human and mouse embryos, the central three planes of individual cells were used to generate a three-plane z-stack. Individual 4,6-diamidino-2-phenylindole (DAPI)-positive nuclei were used to generate a nuclear mask using the Analyze Particles function on either the DAPI or lineage-associated transcription factor channel. The adjacent cytoplasmic area was drawn individually for each nucleus and the mean fluorescence of each region was measured, and the ratio computed. When embryos were stained with E-Cadherin, the membrane was delineated to allow for cytoplasmic region of interest determination. When embryos were stained with podocalyxin, the cytoplasmic region of interest was drawn to ensure delineation of a region captures suitable intra-cellular variation allowing for valid normalization. Measurements were computed on raw SMAD2.3 signal. To quantify pSMAD1.5.9 nuclear intensity, a nuclear mask generated on a central three-plane z-stack for each nucleus, and mean fluorescence values were measured. Within each three-plane z-stack, a background fluorescence taken adjacent to or within a cavity of the embryo was used for background normalization ((frac{text{mean nuclear intensity}}{1+text{mean background intensity}})). Background was normalized to (that is, to provide a comparable signal-to-noise ratio) rather than subtracted to account for the variability in laser penetration between experiments and z-planes. In stem cell experiments, nuclear masks were generated, mean fluorescence was measured, and all values were normalized to a control (DMSO) value of 1. To calculate the percentage of cleaved caspase-3-positive or CER1-positive cells, individual cells were manually counted using the cell counter plugin and presented as a percentage of all DAPI-negative or GATA6-positive cells. For 3D spheroid classification, the total number of structures was counted manually using the Cell Counter plugin, and each was assigned to a class of spheroid. For conditioned medium 3D spheroid quantifications, the central three planes of individual spheroids were used to generate a nuclear mask on the DAPI channel, and the mean nuclear pSMAD1.5.9 signal was quantified along with the signal of an acellular region for background normalization. To generate figures, images were processed by generating z-stacks of approximately five to ten planes to allow for visualization of embryo topology with cells on disparate planes followed by consistent adjustment of brightness and contrast.

No statistical method was used to pre-determine sample sizes. Sample sizes are similar to previous publications7,10,24. For characterization of normal development, embryos lacking any of the three lineages were excluded. Multiple SMAD fluorescence intensities were taken per lineage per embryo. All embryos were included in functional experiments and each cell type count is taken from individual embryos. All stem cell experiments were performed independently at least twice. Investigators were not blinded to group allocation during the experiment or analysis, as blinding would not have been possible due to medium preparation and changing requirements. Group allocation was not performed randomly; rather, based on visual assessment of embryos, investigators attempted to ensure balanced distributions of blastocysts/implanting embryos assessed as expanded with nice inner cell masses versus embryos that appeared delayed or with visible cell death across experimental groups. Statistical tests, except the Bayesian distribution model, were performed in Prism 9 (GraphPad), and where relevant, two-sided tests were used. Normality was tested with a ShapiroWilk test. Bayesian distribution modelling, which is suited to the small sample sizes used in human embryo studies, was used as a supplemental tool to assess how each small-molecule treatment affected the distribution of cell number. To do this, the brms R package was used98,99, with the assumption of a Poisson distribution and the Control counts set to inform the priors and be used as reference. Brms default Markov chain Monte Carlo settings were used. Coefficient credible intervals were either below 0.33, denoting a decrease in the distribution compared to control, or above 0.33, indicating an increase in the distribution compared to control. Credible intervals that bridged this range indicate no significant difference. All coefficients and credible intervals in addition to MannWhitney test P values are presented in Supplementary Table 8. For data presentation, box plots encompass the 25th to 75th percentile in the box, with the median marked by the central line, and the mean marked by a cross. The minimum and maximum are marked by the whiskers. For violin plots, the dashed line marks the median value and dotted lines mark the 25th and 75th percentiles. For summary plots (for example, Fig. 2h,i), the mean standard error of the mean is plotted.

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

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Distinct pathways drive anterior hypoblast specification in the implanting human embryo - Nature.com

Confronting IVF: Human Embryos Are Persons With a Right to Life – Walter Bradley Center for Natural and Artificial Intelligence

By Embryonic Stem Cells

On Sunday I posted on the Alabama Supreme Courts ruling that frozen embryos are considered children (i.e., minor persons) under Alabama law. The decision is well-reasoned and legally correct, and it highlights the profound ethical issues that accompany in vitro fertilization (IVF) of human beings. In that post, I also commented on Yale neurologist Steven Novellas uninformed opinion on the legal decision.

In that same post, Frozen embryos are not people, Novella offers an opinion on the ethics of IVF that is more thoughtful. I disagree with his conclusion that human embryos are not persons from an ethical standpoint. Ill examine his view step by step, and then provide my own.

Novella:

I [lay] out the core question here when does a clump of cells become a person? Standard rhetoric in the anti-abortion community is to frame the question differently, claiming that from the point of fertilization we have human life. But from a legal, moral, and ethical perspective, that is not the relevant question. My colon is human life, but its not a person. Similarly, a frozen clump of cells is not a child.

What is a potential human?

Unlike many people who deny the personhood of very young human beings, Novella recognizes the obvious scientific fact that human life begins at fertilization and that zygotes/embryos/fetuses/newborns are human beings. They are not potential humans.

A sperm and an egg separately constitute a potential human. But when they unite, the result is a human being from the moment of fertilization. Human beings are not defined by the number of cells in the body be it one cell or 30 trillion cells. A big complex human being is not more human than a small simple human being.

There is no actual debate about this the basic biology of human reproduction was understood in the early 19th century, and any doctor or scientist who denies the humanity of a human being in the womb is either ignorant or deliberately misrepresenting science to advance an ideological agenda. I have explained the scientific fact that human life begins at fertilization here.

And the colon? Novellas invocation of his colon in this debate is nonsense. A colon is an organ its a part of a person, not a whole person. A colon is not a human life. An embryo is a human life, even though he or she is much simpler than Dr. Novellas colon or any other part of an adults body.

This is just basic biology, which Dr. Novella should know.

What is a person?

There are two issues in the IVF debate the question of humanity of the embryo and the question of the personhood of the embryo. They are different questions. The fact that an embryo is a human being is not debatable. But the question Is an embryo a person is another matter, and it is debatable.

What is a person? Novella believes that an embryo is a potential person:

those cells have the potential to become a person. But the potential to become a thing is not the same as being a thing. If allowed to develop those cells have the potential to become a person but they are not a person.

So, according to Novella, what confers personhood on a human being? He states:

The real debate comes down to ethical philosophy and legal theory. How do we balance these various facts:

A human embryo is a human, but not sentient.

Sentience and personhood develops gradually throughout the pregnancy.

Fetuses are dependent on the life of their mother until they develop sufficiently to be viable outside the womb.

Pregnancy is a serious biological process with significant implications for the life of the mother.

Sentience and independence

Novella equates personhood with sentience and independence. Sentience and independence are certainly characteristic of most persons we know (including ourselves), but they are not satisfactory criteria for personhood.

A newborn baby, a person with severe mental handicaps, and a person in a deep coma all lack appreciable sentience and independence but they are undoubtedly persons. Using sentience and independence as fundamental criteria for personhood even implies that temporary unconsciousness such as non-sentience during deep sleep or dependence on others such as being critically ill renders us transient non-persons. In fact, we are persons even when we are non-sentient and dependent on others.

Even more disturbing is the fact that gradations of sentience have long been used to deny basic human rights to categories of people based on real or perceived cognitive differences. An illiterate man is, in a very real sense, less sentient than a literate genius, but is he less of a person?

So what, exactly, is a person? Many different definitions have been offered, but it seems to me that there is one continuous thread that runs through what it means to be a person: a person is a human being who has rights and who is entitled to respect. Certainly, to deny a human being any respect and to deny him all rights is to deny his personhood in a fundamental way.

Most rights of persons are linked to particular acquired skills or milestones in the persons life the right to drive a car, the right to vote, the right to keep and bear arms, etc. Yet there is one right that is not linked to skills or milestones, and it is in fact the right on which all other rights depend the right to life. If I am a person with the right to drive and vote and so on, but not the right to life, my life can therefore be taken from me arbitrarily at the whim of another. Then I really dont have any rights at all, and I am not treated as a person. All other rights are meaningless without the right to life.

The right to life is the indispensable cornerstone of all rights, and the right to life is the cornerstone of personhood. Thus a person is a human being with a right to life.

Are all human beings persons? Or are there two classes of humans?

This is the crux of the debate about IVF, abortion, and other life issues: are all human beings persons with an unalienable right to life? Those of us in the pro-life movement answer that question emphatically in the affirmative. Those who support the destruction of human beings in the womb or in the petri dish, etc., believe there are two classes of human beings: those with the right to life, and those without the right to life. This is the issue at hand.

It is certainly the case that in pregnancy and in the production of frozen embryos there are other rights involved the rights of the mother, the rights of the parents (although, of course, to refer to mother and parents implicitly affirms that the unborn are children, not lumps of cells). In sorting out these various rights the right to bodily autonomy, the right to dispose of property, etc. the right to life always takes precedence.

The right to life is the cornerstone of all rights, and even when the rights of the mother or parents are significant and generally worthy of protection, they do not trump the right to life of the young human being the young person in the womb or in the petri dish or in the nursery.

The implications of IVF

A deeply troubling social and moral issue arises with IVF as well. IVF is the industrial manufacture of human beings. The brave new world that is dawning on us has risks and horrors that should chill us. IVF provides the opportunity to screen embryonic human beings for genetic traits (which is already being done), and this technology can and will be used in the future to breed human beings with certain desired traits obsequious servants, aggressive warriors, attractive sex slaves, and compliant organ donors.

We are learning to mass produce human beings, and although the technology thus far has been used mainly for the sympathetic goal of providing childless couples with children, only a naif would believe that it will end here. The industrial manufacture of human beings opens the door to evil on a scale that is the stuff of nightmares.

IVF is an ethically problematic technology with horrifying implications. If we are to survive this brave new world of mass-produced children, conceived not via conjugal love of a husband and wife in a family but via a pipette in a human assembly line, we must affirm that human life begins at fertilization, and that all human beings are persons with the right to life and deserving of respect. This is the essence of the pro-life movement and the philosophy of human exceptionalism. It is stated most cogently in the Christian view that we are created in Gods image. It is that Image that confers personhood and the unalienable right to life on each of us, from fertilization to natural death.

You may also wish to read: Are IVF human embryos children? A recent court decision Neurologist Steven Novella claims that the Alabama Supreme Court ruling that they are children under the law essentially referenced god The ruling not only did not reference God, it was meticulously based on precedent. So those who seek to remove protection from IVF embryos must lobby for that.

See more here:
Confronting IVF: Human Embryos Are Persons With a Right to Life - Walter Bradley Center for Natural and Artificial Intelligence

Striving to Support Gender Equality in Health Care – City of Hope

By Stem Cell Medicine

Nadia Carlesso, M.D., Ph.D.

As a member of the newest class of 24 women selected nationwide to participate in the Carol Emmott Fellowship, Nadia Carlesso, M.D., Ph.D., wants to take this unique and competitive opportunity to move the needle in advancing diversity, equity and inclusion (DEI) on both sides of the research bench.

The Carol Emmott Foundation is a national nonprofit organization that is dedicated to achieving fully inclusive gender equality in health care leadership and governance. The fellowship includes a 14-month experience in which fellows can receive mentorship for their personal projects that support gender equity in health care.

Based on the Duarte, California, campus, Carlesso joined City of Hope in 2016. She is currently professor and chair of the Department of Stem Cell Biology and Regenerative Medicine.

As a scientist in the stem cell field and as chair of the Department of Stem Cell Biology and Regenerative Medicine, I feel the responsibility and commitment to contribute, in the measure I can, to decreasing health disparities in the areas of innovative cell and gene therapies, Carlesso said.

Carlesso said health disparities exist in some part due to the prohibitive costs associated with getting treatment and participating in clinical trials.

We are living in exciting times in terms of the progress and availability of cell and gene therapies potentially curative therapies, she said. But these products have a high cost that can unfortunately widen the care gap. Access to innovative therapies is expensive for many complex reasons. As a community, scientists, technologists and health care professionals must come together to be part of the solution.

There's no easy answer, and not a problem that will be resolved tomorrow, but the conversation has started within scientific circles, and Carlesso wants to further that dialogue and parlay it into actions that can truly make progress.

One step in the right direction is to increase diversity within the scientific community in all aspects, in the name of advancing clinical knowledge.

City of Hope is a diverse and inclusive organization, and I would like to leverage that commitment, Carlesso said. The Emmott Fellowship has given me the opportunity to focus more intently on growing the diversity within our scientific environment.

Innovative biomedical research flourishes when people with different perspectives, experience and skills are empowered to explore new ideas and to work collaboratively and inclusively, she continued. Recruiting, training, retaining and nurturing a workforce representing all dimensions of diversity is critical for the development and implementation of leading-edge therapies that can reach underserved populations. These communities have not had their voices heard: Targeting these communities to be active participants of this specialized workforce and future leaders in this sector is key to decrease barriers to health equity.

Another key step toward this goal is to increase awareness among these communities that their voices are important.

There is not sufficient knowledge out there that they are needed, Carlesso explained. There are cultural biases that have to be overcome. If patients can see themselves in our medical and scientific staff, they will feel more represented and more comfortable that their best interests are at heart.

As an Emmott Fellow, Carlesso said she has identified three areas that she wishes to address in her research project.

The first part is for me to get the numbers, to look at the current diversity within our clinical trials, within our GMP teams, clinical trial coordinators, research nurses, clinicians and basic scientists, she said. At any given time, we have more than 30 investigational new drug applications and 300 clinical trials going on. I want to take advantage of this ideal setting and generate a complete database of the progress weve made, the challenges we still face, and where the bottlenecks are that are compromising diversity and inclusion at all levels.

Establishing a discourse, conversations among peers, is essential to stimulate a reaction toward diversity in research that will benefit all of us, Carlesso said.

A cohesive stem cell research community is critical not only to generate discoveries but also to bring awareness in health disparities and generate synergistic efforts to tackle this problem, she said.

Carlesso maintained that we can empower patients by empowering a diverse workforce, and one way we can do that is to recruit individuals from diverse backgrounds into careers in science, technology, engineering and math (STEM).

A powerful way to give a voice to underserved communities and people of underrepresented backgrounds, and to mitigate health disparities, is to train a workforce that represents them, she said. If underserved families start to have kids going to high school and college doing internships in science and contemplating a carrier in nursing, biomanufacturing, research, then they will have more information, more access and will be less afraid to ask and to pursue more advanced therapeutic solutions or participate to clinical trials.

City of Hope is committed to training the next generation of leaders in stem cells, gene therapy and regenerative medicine, and in fostering an inclusive and safe environment that embraces diversity. Our laboratories host interns every year from the California Institute for Regenerative Medicine bridge program, for example, and we recruit from all communities for our Eugene and Ruth Roberts Summer Student Academy. We also partner with California State Universities in our area and local high schools near the Duarte campus to grow the interest in STEM careers.

As an organization, we need to know that our research has great potential and is helping to close the care gap between socially economically disadvantaged groups and others, Carlesso said. Knowing where we are now is important, so we can define where we are going and how we are going to get there.

I am very excited and thankful to have been chosen for the Emmott Fellowship and the opportunities it represents, she said. I am thrilled and look forward to what I can learn, accomplish and change for the better in my work.

Learn more about the Carol Emmott Fellowship, Carlesso and other members of the Class of 2024, here.

Read the original here:
Striving to Support Gender Equality in Health Care - City of Hope

Transitioning from traditional surgical methods to the innovative use of stem cells – pharmaphorum

By Stem Cell Medicine

Patient lives are being transformed by a transitioning from traditional surgical methods to the innovative use of stem cells.

In todays podcast, host Nicole Raleigh welcomes Dr Jeffrey Gross, founder of ReCELLebrate, neurological surgeon, and expert in the field of regenerative medicine, to discuss this development. Their conversation delves into the recent appetite for the use of stem cells for longevity and explores the health span notion that is being ever more frequently spoken of.

But, essentially, regenerative medicine deals with the functional restoration of specific tissue and/or organ of patients, patients who might be suffering from severe injuries or chronic disease conditions, and who are in a state where the bodys own regenerative responses do not suffice and that is where stem cells, endorsed with indefinite cell division potential and the ability to transdifferentiate into other types of cells, are emerging as a frontline regenerative medicine source.

Yet, when it come to health and vitality, and to epigenetics and prolonged health, scepticism remains and Dr Gross attempts to demystify the landscape for listeners on that, too, including especially the most regenerative source of stem cells: the placenta.

You can listen to episode 121a of thepharmaphorum podcastin the player below, download the episode to your computer, or find it - and subscribe to the rest of the series - iniTunes,Spotify,acast,Stitcher,andPodbean.

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Transitioning from traditional surgical methods to the innovative use of stem cells - pharmaphorum

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