The remarkable similarity between non-human primates(NHPs)and humans establishes them as essential models for understanding human biology and diseases,as well as for developing novel therapeutic strategies,thereby pro...The remarkable similarity between non-human primates(NHPs)and humans establishes them as essential models for understanding human biology and diseases,as well as for developing novel therapeutic strategies,thereby providing more comprehensive reference data for clinical treatment.Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries.As continue to harness the potential of these biotechnological therapies,NHPs are increasingly being employed in preclinical trials,serving as a pivotal tool to evaluate the safety and efficacy of these interventions.Here,we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.展开更多
Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be hig...Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.展开更多
基金supported by grants from the National Key R&D Program of China(2021YFA0805700)the National Natural Science Foundation of China(U2102204)the Natural Science Foundation of Yunnan Province(202001BC070001 and 202102AA100053).
文摘The remarkable similarity between non-human primates(NHPs)and humans establishes them as essential models for understanding human biology and diseases,as well as for developing novel therapeutic strategies,thereby providing more comprehensive reference data for clinical treatment.Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries.As continue to harness the potential of these biotechnological therapies,NHPs are increasingly being employed in preclinical trials,serving as a pivotal tool to evaluate the safety and efficacy of these interventions.Here,we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.
基金supported by grants from the National Key R&D Program of China(2021YFA0805700 and 2021YFA1102000)the National Natural Science Foundation of China(U2102204)the Natural Science Foundation of Yunnan Province(202001BC070001 and 202102AA100053).
文摘Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.
