Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF.Human embryonic stem cells(ES)provide an alternative source for mesenchymal stem cells(MSCs)because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics.Embryonic stem cell-derived mesenchymal stem cells(ES-MSCs)are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs.However,possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells(BMMSCs)in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF.Either human ES-MSCs or BMMSCs were transplanted into these mice.Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ESMSCs and/or BM-MSCs,we evaluated body weight,estrous cyclicity,folliclestimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation.Moreover,terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling,real-time PCR,Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation.Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor,insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTS The human ES-MSCs significantly restored hormone secretion,survival rate and reproductive function in POF mice,which was similar to the results obtained with BM-MSCs.Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles.Notably,the transplanted mice generated new offspring.The results of different analyses showed increases in antiapoptotic and trophic proteins and genes.CONCLUSION These results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility.The possible mechanisms of human ES-MSC were related to promotion of follicular development,ovarian secretion,fertility via a paracrine effect and ovarian cell survival.

Noggin versus basic fibroblast growth factor on the differentiation of human embryonic stem cells

The difference between Noggin and basic fibroblast growth factor for the neural precursor differen- tiation from human embryonic stem cells has not been studied. In this study, 100 tJg/L Noggin or 20 IJg/L basic fibroblast growth factor in serum-free neural induction medium was used to differen- tiate human embryonic stem cells H14 into neural precursors using monolayer differentiation. Two weeks after induction, significantly higher numbers of neural rosettes formed in the Noggin-induced group than the basic fibroblast growth factor-induced group, as detected by phase contrast micro- scope. Immunofluorescence staining revealed expression levels of Nestin, [3-111 Tubulin and Sox-1 were higher in the induced cells and reverse-transcription PCR showed induced cells expressed Nestin, Sox-1 and Neurofilament mRNA. Protein and mRNA expression in the Noggin-induced group was increased compared with the basic fibroblast growth factor-induced group. Noggin has a greater effect than basic fibroblast growth factor on the induction of human embryonic stem cell differentiation into neural precursors by monolayer differentiation, as Noggin accelerates and in- creases the differentiation of neural precursors.

The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells

This study aimed to compare epithelial cells derived from human embryonic stem cells(hESCs) to human ameloblast-lineage cells (ALCs),as a way to determine their potential use as a cell source for ameloblast regeneration.Induced by various concentrations of bone morphogenetic protein 4(BMP4),retinoic acid(RA) and lithium chloride(LiCI) for 7 days,hESCs adopted cobble-stone epithelial phenotype(hESC-derived epithelial cells(ES-ECs)) and expressed cytokeratin 14.Compared with ALCs and oral epithelial cells(OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs.ES-ECs were compared with human fetal skin epithelium,human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well.ALCs had relatively high expression levels of cytokeratin 76,which was also found to be upregulated in ES-ECs.Based on the present study,with the similarity of gene expression with ALCs,ES-ECs are a promising potential cell source for regeneration,which are not available in erupted human teeth for regeneration of enamel.

Tyrosine hydroxylase-positive cells and dopaminergic neuronal function in human embryonic stem cells: An electrophysiological validation

BACKGROUND： Induced differentiation strategies and cytochemical properties of human embryonic stem ceils （hESCs） have been investigated. However, the electrophysiological functions of tyrosine hydroxylase （TH）-positive cells dedved from hESCs remain unclear. OBJECTIVE： To investigate the differentiation efficiency of TH-positive cells from hESCs in vitro using modified four-step culture methods, including embryoid body formation, and to examine the functional characteristics of the differentiated TH-positive cells using electrophysiological techniques. DESIGN, TIME AND SETTING： Neuroelectrophysiology was performed at the Reproductive Medicine Center and Stem Cell Research Center, Peking University Third Hospital, and the Neuroscience Research Institute and Department of Neurobiology, Peking University, from September 2004 to August 2008. MATERIALS： The hESC line, PKU-1.1, a monoclonal cell line derived from a pre-implantation human blastocyst in the Reproductive Medical Center of Peking University Third Hospital. The patch clamp recording system was provided by the Neuroscience Research Institute and Department of Neurobiology, Peking University. METHODS： The hESC line was induced to differentiate into TH-positive cells in vitro using a modified four-step culture method, including the formation of embryoid body, as well as the presence of sonic hedgehog and fibroblast growth factor 8. The cell karyotype was assessed by G-banding karyotype analysis techniques and specific markers were detected immunocytochemically. Whole-cell configuration was obtained after obtaining a tight seal of over 1 GΩ. Ionic currents were detected by holding the cells at -70 mV and stepping to test voltages between -80 and 40 mV in 10-mV increments in voltage-clamp configuration. MAIN OUTCOME MEASURES： We measured the cell karyotype, specific cell markers, and the electrophysiological properties of the voltage-gated ion channels on the cell membrane of TH-positive dopaminergic cells differentiated from our hESCs line in vitro. RESULTS： The differentiated cells had a consistent appearance, and the majority of cells （〉 90%） expressed TH and β-tubulion, as well as the neural progenitor marker, nestino Cell karyotype analysis demonstrated that all of the hESCs had a stable and normal karyotype （46, XX） after differentiation. In addition, patch clamp recording showed that the 10 recorded TH-positive cells exhibited a fast inward current when the test voltage depolarized to -30 mV, and a delayed outward current when the test voltage depolarized to -10 mV. The peak of inward current was obtained at voltage between 10 mV and 0 mV, while the peak of outward current was obtained at 40 mV. The average peak of inward current density was （ -50.05 ± 15.50） pA/pF, and the average peak of outward current density was （41.98 ± 13.55） pA/pE CONCLUSION： More than 90% of the differentiated hESC-derived cells induced by the modified four-step culture method exhibit dopaminergic neuronal properties, including general electrophysiological functional properties, such as functional potassium and sodium channels.

Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells

Overexpression of receptor-interacting protein 140（RIP140） promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2（ERK1/2） signaling.However,involvement of RIP140 in human neural differentiation remains unclear.We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells.Moreover,RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation,and positively correlated with the neural stem cell marker Nestin during later stages.Thus,ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

Human embryonic stem cells as an in vitro model for studying developmental origins of type 2 diabetes

The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.

Developmental toxicity assessment of neonicotinoids and organophosphate esters with a human embryonic stem cell-and metabolism-based fast-screening model

In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to animals.Thus,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during development.We employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals.We show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers up-regulated.Human liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and OPEs.Our findings suggest that NEOs and OPEs interfere with human early embryonic development.

A human embryonic stem cell-based in vitro model revealed that ultrafine carbon particles may cause skin inflammation and psoriasis

Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin,and be absorbed into the bloodstream.Here,we employed a human embryonic stem cell(h ESC)-based differentiation system towards keratinocytes,to test the effects of ultrafine carbon particles,which mimic ambient ultrafine particles,at environment related concentrations.We found that10 ng/mL to 10μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in h ESCs.Moreover,1μg/mL to 10μg/mL carbon particle treatments disrupted the keratinocyte differentiation,and up-regulated inflammationand psoriasis-related genes,such as IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,CXCL8,and S100 A7 and S100 A9,respectively.Overall,our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.

Cytotoxic effects of mono-（2-ethylhexyl） phthalate on human embryonic stem cells

Background Mono-（2-ethylhexyl） phthalate （MEHP）, the metabolite of di-（2-ethylhexyl） phthalate （DEHP）, was suspected to be toxic to human embryos. This study contributes to investigating its toxic effects by an embryonic stem cell test （EST） based on two human embryonic stem cell （hESCs） lines. Methods CH1 established in our own lab and H1, a federally registered cell line were two human embryonic stem cell lines used in this test. Four endpoint measurements were performed consisting of cell viability, proliferation ability, apoptosis as well as changes of gene expression patterns after spontaneous differentiation were determined. For measuring effects on the first three endpoints, the cells were treated with various concentrations of MEHP dissolved in dimethyl sulfoxide （DMSO） and only with DMSO which served as control and harvested after 5 days. For measuring effects during spontaneous differentiation, the RNA of embryoid bodies （EBs） formed after 8 days＇ MEHP exposure was collected and changes in differentiation specific gene expression patterns were analyzed by quantitative real time RT-PCR. Results As a result the viability and proliferation ability of both cell lines decreased significantly at 1000 μmol/L MEHP, while there was no effect on apoptosis or cell morphology. In addition MEHP also changed the gene expression pattern in the EBs of both cell lines. Conclusion MEHP in a high dose was cytotoxic and affected the development of hESCs, which indicates its embryo toxicitv in human embrvos.

Expression and reconstitution of the bioluminescent Ca2+reporter aequorin in human embryonic stem cells,and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

In order to develop a novel method of visualizing possible Ca^(2+) signaling during the early differentiation of h ESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca^(2+) reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca^(2+) signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca^(2+) transients(generated by release from intracellular stores) were detected in 1–12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or Ca Cl_2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor(IP_3R) agonist, small Ca^(2+) transients were generated from day 1 onward. That ATP was inducing Ca^(2+) release from functional IP_3 Rs was demonstrated by treatment with 2-APB, a known IP_3 R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor(Ry R) agonist, a minimal Ca^(2+) response was observed at day 8 of differentiation only. Thus, our data indicate that unlike Ry Rs, IP_3 Rs are present and continually functional at these early stages of cardiomyocyte differentiation.

Derivation and characterization of human embryonic stem cell lines from the Chinese population

Human embryonic stem cells （hESCs） can self-renew indefinitely and differentiate into all cell types in the human body. Therefore, they are valuable in regenerative medicine, human developmental biology and drug discovery. A number of hESC lines have been derived from the Chinese population, but limited of them are available for research purposes. Here we report the derivation and characterization of two hESC lines derived from human blastocysts of Chinese origin. These hESCs express alkaline phosphatase and hESC-specific markers, including Oct4, Nanog, SSEA-3, SSEA-4, TRA- 1-60 and TRA-1-81. They also have high levels of telomerase activity and normal karyotypes. These ceils can form embryoid body in vitro and can be differentiated into all three germ layers in vivo by teratoma formation. The newly established hESCs will be distributed for research purposes. The availability of hESC lines from the Chinese population will facilitate studies on the differences in hESCs from different ethnic groups.

Cryopreservation of human embryonic stem cells by vitrification

Background The efficiency of traditional cryopreservation of human embryonic stem (ES) cells is low, and there have been few attempts to prove new cryopreservation methods effective. This study was designed to evaluate the efficiency of cryopreservation of human ES cells using vitrification method.Methods Human ES cells clumped from an identical cell line were randomly allocated to be cryopreserved by vitrification or by slow freezing. The recovery rates, the growth and differentiation potential of thawed human ES cells were compared between these two groups. The pluripotency of human ES cells after thawing was identified.Results Eighty-one point nine percent (59/72) of human ES cell clumps were recovered after vitrification, while only 22.8% (16/70) were recovered after slow freezing (P<0.01). The colonies after vitrification manifested have not only faster growth but also a lower level of differentiation when compared to colonies subjected to the slow freezing protocol. However, the rates of growth and differentiation in undifferentiated colonies from both groups were identical to the rates in those of non-cryopreserved stem cells after a prolonged culture period. Passage 6 of vitrified human ES cells retained the properties of pluripotent cells, a normal karyotype and expressed the transcription factor OCT-4, stage specific expressed antigen-4 (SSEA-4) and SSEA-3. Teratoma growth of these cells demonstrated the ability to develop into all three germ layers.Conclusions Vitrification is effective in cryopreserving human ES cells. During a prolonged culture, human ES cells retain their pluripotency after cryopreservation.

Derivation and characterization of Chinese human embryonic stem cell line with high potential to differentiate into pancreatic and hepatic cells

Background Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embrvonic stem cell lines with clarified directly differentiation ability

Zichong granules(资冲颗粒)promote differentiation of ovarian granulosa-like cells from human embryonic stem cells in vitro

OBJECTIVE:To investigate whether Zichong granules(资冲颗粒,ZCKL),a very effective herbal formula for treating infertility,have an impact on the differentiation of ovarian granulosa cells from human embryonic stem cells(hESCs)in vitro,and to explore the cellular mechanisms of its clinical effects.METHODS:Serum from ZCKL-medicated rats was prepared and used to treat mesoderm cells derived from hESCs for 6 d.Normal rat serum and a set of growth factors were used as negative and positive controls,respectively.RESULTS:ZCKL-medicated rat serum,but not normal rat serum,induced hESCs-derived mesoderm cells to differentiate into functional ovarian granulosa-like cells(OGLCs)in a similar manner to defined growth factors.The induced OGLCs resembled the morphology of native human granulosa cells,expressed granulosa cell-specific markers at both the mRNA and protein levels,produced high levels of estradiol and strongly responded to follicle-stimulating hormone stimulation.Furthermore,mRNA levels of follistatin,mothers against decapentaplegic homolog 8 and bone morphogenetic protein 6 were dynamically changed during the process.CONCLUSION:In the ZCKL treatment of infertility,one mechanism by which ZCKL may act is by influencing ovarian granulosa cell differentiation and development,possibly through the follistatin and BMP/SMAD signaling pathways.

Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities,but effective clinical interventions for restoring neurological functions have yet to be developed.In early spinal cord development,neural progenitors of the motor neuron(pMN)domain,defined by the expression of oligodendrocyte transcription factor 2(OLIG2),in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes.Given their differentiation potential,pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury.However,fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging.In this study,based on chemical screening,we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells.More importantly,these OLIG2+pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly.Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Consistent apparent Young’s modulus of human embryonic stem cells and derived cell types stabilized by substrate stiffness regulation promotes lineage specificity maintenance

Background:Apparent Young’s modulus(AYM),which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization,has been investigated as potential indicators of cell fate in specific cell types.However,applying biophysical cues,such as modulating the substrate stiffness,to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications,remains a primary challenge during in vitro stem cell expansion.Moreover,substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation,yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion(from single-cell stage to multi-cell stage)has not been established.Results:Here,we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness.Moreover,the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types.Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics.On substrates that were too rigid or too soft,fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity.On a substrate with‘optimal’stiffness(i.e.,3.5 kPa),the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity.The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP.Conclusions:In summary,this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance,through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling.These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.

A versatile tool for tracking the differentiation of human embryonic stem cells

The ability of human embryonic stem cells(hESCs)to undergo indefinite self-renewal in vitro and to produce lineages derived from all three embryonic germ layers both in vitro and in vivo makes such cells extremely valuable in both clinical and research settings.However,the generation of specialized cell lineages from a mixture of differentiated hESCs remains technically difficult.Tissue specific promoter-driven reporter genes are power-ful tools for tracking cell types of interest in differentiated cell populations.Here,we describe the construction of modular lentivectors containing different tissue-specific promoters(Tα1 ofα-tubulin;aP2 of adipocyte Protein 2;and AFP of alpha fetoprotein)driving expression of humanized Renilla greenfluorescent protein(hrGFP).To this end,we used MultiSite gateway technology and employed the novel vectors to successfully monitor hESC differentiation.We present a versatile method permitting target cells to be traced.Our system will facilitate research in developmental biology,transplantation,and in vivo stem cell tracking.

Prostaglandin E2 promotes hematopoietic development from human embryonic stem cells

Recent studies have suggested that prostaglan-din(PG)E2(PGE2)and the prostaglandin pathway are essential for hematopoietic stem cell growth and develop-ment.However,similar studies on hematopoietic commit-ment from human embryonic stem cells(hESCs)are still limited.Here we report that the addition of PGE2 promotes hematopoietic differentiation of hESCs.The induced cells from hESCs/OP9 co-culture and in the presence of PGE2 were characterized by reverse transcription-PCR(RT-PCR),flow cytometry,colony-forming assays and Wright-Giemsa staining.Our results demonstrated that PGE2 exposure could alter the gene expression pattern and morphology of co-cultured hESCs and resulted in a robust hematopoietic differentiation with higher frequencies of CD34+and CD45+cells.Furthermore,the Smad signaling pathway may be involved in PGE2 and OP9 induced hematopoietic differentiation of hESCs.This research may improve our knowledge of stem cell regulation and hopefully lead to better stem cell-based therapeutic options.

ETV2 expression increases the efficiency of primitive endothelial cell derivation from human embryonic stem cells

Background:Endothelial cells line the luminal surface of blood vessels and form a barrier between the blood and other tissues of the body.Ets variant 2(ETV2)is transiently expressed in both zebrafish and mice and is necessary and sufficient for vascular endothelial cell specification.Overexpression of this gene in early zebrafish and mouse embryos results in ectopic appearance of endothelial cells.Ectopic expression of ETV2 in later development results in only a subset of cells responding to the signal.Findings:We have examined the expression pattern of ETV2 in differentiating human embryonic stem cells(ESCs)to determine when the peak of ETV2 expression occurs.We show that overexpression of ETV2 in differentiating human ESC is able to increase the number of endothelial cells generated when administered during or after the endogenous peak of gene expression.Conclusions:Addition of exogenous ETV2 to human ESCs significantly increased the number of cells expressing angioblast genes without arterial or venous specification.This may be a viable solution to generate in vitro endothelial cells for use in research and in the clinic.

For your eyes only:Harnessing human embryonic stem cell-derived retinal pigment epithelial cells to improve impaired vision

Vision loss or impairment resulting from the degeneration of the retinal pigment epithelium and photoreceptor death affects millions worldwide.Recent exciting results from clinical studies of small numbers of patients treated with human embryonic stem cell-derived retinal pigment epithelial cells may provide hope for affected individuals.