Embryonic stem （ES） cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy...Embryonic stem （ES） cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy. ES cells of mouse and human have been successfully generated and applied in a wide range of research. However, no genuine ES cell lines have been obtained from rat to date. In this study, we identified pluripotent cells in early rat embryos using specific antibodies against markers of pluripotent stem ceils. Subsequently, by modifying the culture medium for rat blastocysts, we derived pluripotent rat ES-like cell lines, which expressed pluripotency markers and formed embryoid bodies （EBs） in vitro. Importantly, these rat ES-like cells were able to produce teratomas. Both EBs and teratomas contained tissues from all three embryonic germ layers. In addition, from the rat ES-like cells, we derived a rat primitive endoderm （PrE） cell line. Furthermore, we conducted transcriptional profiling of the rat ES-like cells and identified the unique molecular signature of the rat pluripotent stem cells. Our analysis demonstrates that multiple signaling pathways, including the BMP, Activin and mTOR pathways, may be involved in keeping the rat ES-like cells in an undifferentiated state. The cell lines and information obtained in this study will accelerate our understanding of the molecular regulation underlying pluripotency and guide us in the appropriate manipulation of ES cells from a particular species.展开更多
Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the ide...Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.展开更多
In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongo...In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.展开更多
Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of variou...Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases.In this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic organoids.We also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this technology.Finally,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.展开更多
Recently we have established a new culture condition enabling the derivation of extended pluripotent stem(EPS)cells,which,compared to conventional pluripotent stem cells,possess superior developmental potential and ge...Recently we have established a new culture condition enabling the derivation of extended pluripotent stem(EPS)cells,which,compared to conventional pluripotent stem cells,possess superior developmental potential and germline competence.However,it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment.Here,we show that EPS cells can be robustly generated from non-permissive NOD-sc/d Il2rg 1 mice through de novo derivation from blastocysts.Furthermore,these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-sc/d II2rg-/-fibroblasts.NOD-sc/d II2rg-/-EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting.Notably,these cells contribute to both embryonic and extraembryonic lineages in vivo.More importantly,they can produce chimeras and integrate into the E13.5 genital ridge.Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains,which could potentially be a general strategy for deriving mouse pluripotent cells.The generation of NOD-sc/d II2rg-/-Yaqin Du and Ting Wang contributed equally to this work.Electronic supplementary material The online version of this article(https://doi.org/10.1007/s13238-018-0558-z)contains supplementary material,which is available to authorized users.EPS cell lines permits sophisticated genetic modification in NOD-scid II2rg-/-mice,which may greatly advance the optimization of humanized mouse models for biomedical applications.展开更多
文摘Embryonic stem （ES） cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy. ES cells of mouse and human have been successfully generated and applied in a wide range of research. However, no genuine ES cell lines have been obtained from rat to date. In this study, we identified pluripotent cells in early rat embryos using specific antibodies against markers of pluripotent stem ceils. Subsequently, by modifying the culture medium for rat blastocysts, we derived pluripotent rat ES-like cell lines, which expressed pluripotency markers and formed embryoid bodies （EBs） in vitro. Importantly, these rat ES-like cells were able to produce teratomas. Both EBs and teratomas contained tissues from all three embryonic germ layers. In addition, from the rat ES-like cells, we derived a rat primitive endoderm （PrE） cell line. Furthermore, we conducted transcriptional profiling of the rat ES-like cells and identified the unique molecular signature of the rat pluripotent stem cells. Our analysis demonstrates that multiple signaling pathways, including the BMP, Activin and mTOR pathways, may be involved in keeping the rat ES-like cells in an undifferentiated state. The cell lines and information obtained in this study will accelerate our understanding of the molecular regulation underlying pluripotency and guide us in the appropriate manipulation of ES cells from a particular species.
基金Supported by the Korea Health Technology RD Project through the Korea Health Industry Development Institutethe Ministry of Health and Welfare,No.HI16C-2207+1 种基金the Basic Science Research Program through the NRF,No.NRF-2018R1D1A1A09083264Ewha Womans University,No.RP-grant2017
文摘Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.
基金National Natural Science Foundation of China,No.81271122 and No.81371122Shanghai Leading Academic Discipline Project,No.S30206
文摘In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.
文摘Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases.In this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic organoids.We also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this technology.Finally,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.
基金the National Key Research and Development Program of China(2016YFA01001002017YFA0103000)+4 种基金the National Natural Science Foundation of China(Grant Nos.31730059 and 31521004)the Guangdong Innovative and En trepreneurial Research Team Program(2014ZT05S216)the Science and Technology Planning Project of Guangdong Province,China(2014B020226001 and 2016B030232001)the Science and Technology Program of Guangzhou,China(201508020001)National Natural Science Foundation of China(Grant No.31571052).
文摘Recently we have established a new culture condition enabling the derivation of extended pluripotent stem(EPS)cells,which,compared to conventional pluripotent stem cells,possess superior developmental potential and germline competence.However,it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment.Here,we show that EPS cells can be robustly generated from non-permissive NOD-sc/d Il2rg 1 mice through de novo derivation from blastocysts.Furthermore,these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-sc/d II2rg-/-fibroblasts.NOD-sc/d II2rg-/-EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting.Notably,these cells contribute to both embryonic and extraembryonic lineages in vivo.More importantly,they can produce chimeras and integrate into the E13.5 genital ridge.Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains,which could potentially be a general strategy for deriving mouse pluripotent cells.The generation of NOD-sc/d II2rg-/-Yaqin Du and Ting Wang contributed equally to this work.Electronic supplementary material The online version of this article(https://doi.org/10.1007/s13238-018-0558-z)contains supplementary material,which is available to authorized users.EPS cell lines permits sophisticated genetic modification in NOD-scid II2rg-/-mice,which may greatly advance the optimization of humanized mouse models for biomedical applications.
