Here we propose that the rejuvenation of leukocytes with iPSC technology in vitro and transfusion of cancer cellresistant white blood cells back to human body provide a prospective therapy for cancer patients.
Stem cell therapies show great potential for use in regenerative medicine, though advancements in safe stem cell technology need to be realized. Human induced pluripotent stem cells (hiPSCs) hold an advantage over oth...Stem cell therapies show great potential for use in regenerative medicine, though advancements in safe stem cell technology need to be realized. Human induced pluripotent stem cells (hiPSCs) hold an advantage over other stem cell types for use in cell-based therapies due to their potential as an unlimited source of rejuvenated and immunocompatible SCs which do not elicit the ethical and moral debates associated with the destruction of human embryos. Towards realization of this potential this review focuses on the recent progress in DNA-and xeno-free reprogramming methods, particularly small molecule methods, as well as addresses some of the latest insights on donor cell gene expression, telomere dynamics, and epigenetic aberrations that are a potential barrier to successful widespread clinical applications.展开更多
Reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, w...Reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification （methylation and acetylation） and DNA modification （methylation） during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations.展开更多
Background Parkinson’s disease(PD)is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic(DA)neurons in the substantia nigra region of the brain.Substantial evidence indicates that ...Background Parkinson’s disease(PD)is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic(DA)neurons in the substantia nigra region of the brain.Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfoldedα-synuclein aggregations.Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD.However,there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function.In addition,the half-life of mitochondria varies between days to a few weeks.Thus,identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes.In this study,we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD.Methods We generated DA neurons and astrocytes from human iPSCs and hESCs.We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer,as well as the neuroprotective effect of mitochondrial transfer.We employed immunocytochemistry and FACS analysis to track mitochondria.Results We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media(ACM)can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model.Specifically,we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media.Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway.Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone.When rotenone injured neurons were cultured in presence of ACM depleted of mitochondria(by ultrafiltration),the neuroprotective effects were abolished.Conclusions Our studies provide the proof of principle that iPSCs-derived astrocytes can act as mitochondria donor to the injured DA neurons and attenuate pathology.Using iPSCs derived astrocytes as a donor can provide a novel strategy that can be further developed for cellular therapy for PD.展开更多
Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA （mtDNA） mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy,...Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA （mtDNA） mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells （MiPSCs） that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes （MELAS）. We engineered mitochondrial-targeted transcription activator-like effector nucleases （mitoTALENs） and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.展开更多
Embryonic stem cells （ESCs） derived from the early embryos possess two important characteristics：self-renewal and pluripotency,which make ESCs ideal seed cells that could be potentially utilized for curing a number...Embryonic stem cells （ESCs） derived from the early embryos possess two important characteristics：self-renewal and pluripotency,which make ESCs ideal seed cells that could be potentially utilized for curing a number of degenerative and genetic diseases clinically.However,ethical concerns and immune rejection after cell transplantation limited the clinical application of ESCs.Fortunately,the recent advances in induced pluripotent stem cell （iPSC） research have clearly shown that differentiated somatic cells from various species could be reprogrammed into pluripotent state by ectopically expressing a combination of several transcription factors,which are highly enriched in ESCs.This ground-breaking achievement could circumvent most of the limitations that ESCs faced.However,it remains challenging if the iPS cell lines,especially the human iPSCs lines,available are fully pluripotent.Therefore,it is prerequisite to establish a molecular standard to distinguish the better quality iPSCs from the inferior ones.展开更多
Differentiated cells can be reprogrammed into pluripotent stem cells,known as“induced pluripotent stem cells”(iPSCs),through the overexpression of defined transcription factors.The creation of iPSC lines has opened ...Differentiated cells can be reprogrammed into pluripotent stem cells,known as“induced pluripotent stem cells”(iPSCs),through the overexpression of defined transcription factors.The creation of iPSC lines has opened new avenues for patient-specific cell replacement therapies for regenerative medicine.However,the clinical utilization of iPSCs is largely impeded by two limitations.The first limitation is the low efficiency of iPSCs generation from differentiated cells.The second limitation is that many iPSC lines are not authentically pluripotent,as many cell lines inefficiently differentiate into differentiated cell types when they are tested for their ability to complement embryonic development.Thus,the“quality”of iPSCs must be increased if they are to be differentiated into specialized cell types for cell replacement therapies.Overcoming these two limitations is paramount to facilitate the widespread employment of iPSCs for therapeutic purposes.Here,we summarize recent progress made in strategies enabling the efficient production of high-quality iPSCs,including choice of reprogramming factors,choice of target cell type,and strategies to improve iPSC quality.展开更多
Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compen...Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.展开更多
A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and d...A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and diseases.Herein,we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells(NPCs)from human ESC/iPSCs on Type I Collagen.The derived cells not only displayed the requisite markers,but also behaved similarly to classic NPCs both in vitro and in vivo.Upon transplantation into traumatic brain injury model,the derived NPCs facilitated recovery from injury.We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen,and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day.Meanwhile,ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction.Totally,our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases’treatment.展开更多
The breakthrough invention of induced pluripotent stem cells(iPSCs)ignited huge excitement with the promise of unlimited autologous cell sources for future regenerative medicine.1,2 However,before this expectation tur...The breakthrough invention of induced pluripotent stem cells(iPSCs)ignited huge excitement with the promise of unlimited autologous cell sources for future regenerative medicine.1,2 However,before this expectation turns into reality the safety and efficacy of these autologous cell products have to be meticulously evaluated and validated.Towards this end much research effort has been concentrated on three clinically relevant aspects:tumorigenesis,immunogenesis,and efficacy.展开更多
It is well recognized that transcription factor-induced iPSCs carry an aberrant genetic and epigenetic makeup.However,it is not clear whether these defects are developed de novo due to the reprogramming process or inh...It is well recognized that transcription factor-induced iPSCs carry an aberrant genetic and epigenetic makeup.However,it is not clear whether these defects are developed de novo due to the reprogramming process or inherited from the somatic source cells.Ma and colleagues presented convincing data that iPSCs derived through transcription factor over-expression carry a higher incidence of the epigenetic flaws in comparison with those generated through SCNT.The authors conclude that 1)the source of the epigenetic aberrations is more related to the reprogramming protocol,and less to the intrinsic abnormality of the somatic source cells;2)SCNT based protocol is superior to that involving a cocktail of transcription factors.These important findings by Ma and colleagues will certainly steer future research towards understanding the mechanisms underpinning the SCNTreprogramming.With these efforts a whole array of unknown factors is expected to emerge,which regulate the onset of early embryonic development and can be applied to induce iPSCs with a healthier epigenetic landscape.展开更多
In 2006,Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4,Sox2,Klf44,and c-Myc.Since then,the...In 2006,Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4,Sox2,Klf44,and c-Myc.Since then,the future clinical application of somatic cell reprogramming technology has become an attractive research topic in the field of regenerative medicine.Of note,considerable interest has been placed in circumventing ethical issues linked to embryonic stem cell research.However,tumorigenicity,immunogenicity,and heterogeneity may hamper attempts to deploy this technology therapeutically.This review highlights the progress aimed at reducing induced pluripotent stem cells tumorigenicity risk and howto assess the safety of induced pluripotent stem cells cell therapy products.展开更多
文摘Here we propose that the rejuvenation of leukocytes with iPSC technology in vitro and transfusion of cancer cellresistant white blood cells back to human body provide a prospective therapy for cancer patients.
文摘Stem cell therapies show great potential for use in regenerative medicine, though advancements in safe stem cell technology need to be realized. Human induced pluripotent stem cells (hiPSCs) hold an advantage over other stem cell types for use in cell-based therapies due to their potential as an unlimited source of rejuvenated and immunocompatible SCs which do not elicit the ethical and moral debates associated with the destruction of human embryos. Towards realization of this potential this review focuses on the recent progress in DNA-and xeno-free reprogramming methods, particularly small molecule methods, as well as addresses some of the latest insights on donor cell gene expression, telomere dynamics, and epigenetic aberrations that are a potential barrier to successful widespread clinical applications.
基金supported by the Lundbeck Foundation(No.R151-2013-14439)the Danish Research Council for Independent Research(No.16942)
文摘Reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification （methylation and acetylation） and DNA modification （methylation） during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations.
基金This work was in part supported by grants from RO1HD087566,RO1HD091325National Natural Science Foundation of China(81801258)+1 种基金Youth fund of Jiangsu Province’s natural science foundation(BK20170355)Gusu Health Talents Training Project(GSWS2019041).
文摘Background Parkinson’s disease(PD)is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic(DA)neurons in the substantia nigra region of the brain.Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfoldedα-synuclein aggregations.Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD.However,there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function.In addition,the half-life of mitochondria varies between days to a few weeks.Thus,identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes.In this study,we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD.Methods We generated DA neurons and astrocytes from human iPSCs and hESCs.We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer,as well as the neuroprotective effect of mitochondrial transfer.We employed immunocytochemistry and FACS analysis to track mitochondria.Results We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media(ACM)can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model.Specifically,we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media.Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway.Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone.When rotenone injured neurons were cultured in presence of ACM depleted of mitochondria(by ultrafiltration),the neuroprotective effects were abolished.Conclusions Our studies provide the proof of principle that iPSCs-derived astrocytes can act as mitochondria donor to the injured DA neurons and attenuate pathology.Using iPSCs derived astrocytes as a donor can provide a novel strategy that can be further developed for cellular therapy for PD.
基金This work was supported in part by the ＂Reproductive health and major birth defects prevention and control research＂ Key Special Fund （No. 2016YFC1000601）, the National Natural Science Foundation of China （Grant Nos. 31371521, 81370766, 81401254, 81570101, 81671121, 31601187, 81521002）, the Guangdong Province Science and Technology Project （2014TQ01R683, 2017A020 214005, 2016A020216023, 2015A030310119, 2016B030229008）, the Bureau of Science and Technology of Guangzhou Municipality （201505011111498）, the ＂Reproductive health and major birth defects prevention and control research＂ Key Special Fund （Nos. 2016YFC1000201 and 2016YFC1000302）, the Ministry of Science and Technology of China Grants （973 program 2014CB943203）, and the Beijing Nova Program （xxjh2015011）.
文摘Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA （mtDNA） mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells （MiPSCs） that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes （MELAS）. We engineered mitochondrial-targeted transcription activator-like effector nucleases （mitoTALENs） and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
基金supported by the grants from the Ministry of Science and Technology of China (Nos 2008AA022311,2010CB944900 and 2008AA1011005)
文摘Embryonic stem cells （ESCs） derived from the early embryos possess two important characteristics：self-renewal and pluripotency,which make ESCs ideal seed cells that could be potentially utilized for curing a number of degenerative and genetic diseases clinically.However,ethical concerns and immune rejection after cell transplantation limited the clinical application of ESCs.Fortunately,the recent advances in induced pluripotent stem cell （iPSC） research have clearly shown that differentiated somatic cells from various species could be reprogrammed into pluripotent state by ectopically expressing a combination of several transcription factors,which are highly enriched in ESCs.This ground-breaking achievement could circumvent most of the limitations that ESCs faced.However,it remains challenging if the iPS cell lines,especially the human iPSCs lines,available are fully pluripotent.Therefore,it is prerequisite to establish a molecular standard to distinguish the better quality iPSCs from the inferior ones.
基金partially funded by Program for New Century Excellent Talents in University(NCET-11-0482)by the National Key Basic Research and Development Program of China(Nos.2009CB941003,2011CBA01102,2011CBA01001,and 2010CB945404).
文摘Differentiated cells can be reprogrammed into pluripotent stem cells,known as“induced pluripotent stem cells”(iPSCs),through the overexpression of defined transcription factors.The creation of iPSC lines has opened new avenues for patient-specific cell replacement therapies for regenerative medicine.However,the clinical utilization of iPSCs is largely impeded by two limitations.The first limitation is the low efficiency of iPSCs generation from differentiated cells.The second limitation is that many iPSC lines are not authentically pluripotent,as many cell lines inefficiently differentiate into differentiated cell types when they are tested for their ability to complement embryonic development.Thus,the“quality”of iPSCs must be increased if they are to be differentiated into specialized cell types for cell replacement therapies.Overcoming these two limitations is paramount to facilitate the widespread employment of iPSCs for therapeutic purposes.Here,we summarize recent progress made in strategies enabling the efficient production of high-quality iPSCs,including choice of reprogramming factors,choice of target cell type,and strategies to improve iPSC quality.
文摘Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.
基金supported by the National Key Research and Development Program of China(2017YFA0104800)the“Strategic Priority Research Program”of the Chinese Academy of Sciences(XDA16010505)+5 种基金the National Natural Science Foundation of China(81570944,31300901,and 31900547)Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education FoundationScience and Technology Planning Project of Guangdong Province,China(2017B030314056)Natural Science Foundation of Guangdong Province,China(2017A030310098,2016A030313165,2015A030310026,and 2014A030313732)Science and Technology Planning Project of Guangzhou,China(201904010474)Shenzhen Peacock Plan(KQTD2016113015442590)。
文摘A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and diseases.Herein,we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells(NPCs)from human ESC/iPSCs on Type I Collagen.The derived cells not only displayed the requisite markers,but also behaved similarly to classic NPCs both in vitro and in vivo.Upon transplantation into traumatic brain injury model,the derived NPCs facilitated recovery from injury.We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen,and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day.Meanwhile,ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction.Totally,our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases’treatment.
文摘The breakthrough invention of induced pluripotent stem cells(iPSCs)ignited huge excitement with the promise of unlimited autologous cell sources for future regenerative medicine.1,2 However,before this expectation turns into reality the safety and efficacy of these autologous cell products have to be meticulously evaluated and validated.Towards this end much research effort has been concentrated on three clinically relevant aspects:tumorigenesis,immunogenesis,and efficacy.
文摘It is well recognized that transcription factor-induced iPSCs carry an aberrant genetic and epigenetic makeup.However,it is not clear whether these defects are developed de novo due to the reprogramming process or inherited from the somatic source cells.Ma and colleagues presented convincing data that iPSCs derived through transcription factor over-expression carry a higher incidence of the epigenetic flaws in comparison with those generated through SCNT.The authors conclude that 1)the source of the epigenetic aberrations is more related to the reprogramming protocol,and less to the intrinsic abnormality of the somatic source cells;2)SCNT based protocol is superior to that involving a cocktail of transcription factors.These important findings by Ma and colleagues will certainly steer future research towards understanding the mechanisms underpinning the SCNTreprogramming.With these efforts a whole array of unknown factors is expected to emerge,which regulate the onset of early embryonic development and can be applied to induce iPSCs with a healthier epigenetic landscape.
基金We thank the National Natural Science Foundation of China(grants No.32171387 and 32071452)Shenzhen Bay Laboratory Open Program(grant No.SZBL2020090501003)the Pearl River Talents Program Local Innovative and Research Teams(grant No.2017BT01S131).
文摘In 2006,Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4,Sox2,Klf44,and c-Myc.Since then,the future clinical application of somatic cell reprogramming technology has become an attractive research topic in the field of regenerative medicine.Of note,considerable interest has been placed in circumventing ethical issues linked to embryonic stem cell research.However,tumorigenicity,immunogenicity,and heterogeneity may hamper attempts to deploy this technology therapeutically.This review highlights the progress aimed at reducing induced pluripotent stem cells tumorigenicity risk and howto assess the safety of induced pluripotent stem cells cell therapy products.
