Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells

Li, Weiqiang; Hu, Lihua; Lin, Wanyi; Qin, Ke; Chen, Rui; Lai, Xiaomin; Wang, Xiaoyu; Zhang, Jifeng; Meihua, Jiang; Huang, Weijun; Wang, Tao; Yang, Xuesong; Chen, Yuan; Wu, Song; Xiang, Andy Peng

doi:10.1016/j.biomaterials.2014.10.056

Cited by 18 publications

(7 citation statements)

References 40 publications

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“…Previous research showed that human ESCs and iPSCs can generate central and PNS components from neural precursors via an intermediate rosette stage ( Lee et al., 2010 ). Here, we cultured CMT1A hiPSCs under conditions designed to generate NCSCs via EB formation, as previously described ( Li et al., 2015 ). When EBs were adherently cultured in neural crest induction medium, neural rosettes emerged after 3 days of culture ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs

Shi

et al. 2018

Stem Cell Reports

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SummaryCharcot-Marie-Tooth disease type 1A (CMT1A), one of the most frequent inherited peripheral neuropathies, is associated with PMP22 gene duplication. Previous studies of CMT1A mainly relied on rodent models, and it is not yet clear how PMP22 overexpression leads to the phenotype in patients. Here, we generated the human induced pluripotent stem cell (hiPSC) lines from two CMT1A patients as an in vitro cell model. We found that, unlike the normal control cells, CMT1A hiPSCs rarely generated Schwann cells through neural crest stem cells (NCSCs). Instead, CMT1A NCSCs produced numerous endoneurial fibroblast-like cells in the Schwann cell differentiation system, and similar results were obtained in a PMP22-overexpressing iPSC model. Therefore, despite the demyelination-remyelination and/or dysmyelination theory for CMT1A pathogenesis, developmental disabilities of Schwann cells may be considered as an underlying cause of CMT1A. Our results may have important implications for the uncovering of the underlying mechanism and the development of a promising therapeutic strategy for CMT1A neuropathy.

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Section: Resultsmentioning

confidence: 99%

Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs

Shi

et al. 2018

Stem Cell Reports

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“…The next step was to confirm the identity of cells migrating out from the DRG. The low-affinity neurotrophin receptor (P75)—a transmembrane glycoprotein—is expressed in enteric NCSCs and glial cells 40 and has been used as a selection marker for successfully isolating NCSCs from the gut tissue of mice and humans 41–43 . In combination with the NCSCs marker Sox10 and neural stem cell (NSC) marker Nestin, P75 was used to identify the NCSCs from the DRG.…”

Section: Resultsmentioning

confidence: 99%

DRG-Derived Neural Progenitors Differentiate into Functional Enteric Neurons Following Transplantation in the Postnatal Colon

Ding

et al. 2018

Cell Transplant

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Cell therapy has great promise for treating gastrointestinal motility disorders caused by intestinal nervous system (ENS) diseases. However, appropriate sources, other than enteric neural stem cells and human embryonic stem cells, are seldom reported. Here, we show that neural progenitors derived from the dorsal root ganglion (DRG) of EGFP mice survived, differentiated into enteric neurons and glia cells, migrated widely from the site of injection, and established neuron-muscle connections following transplantation into the distal colon of postnatal mice. The exogenous EGFP+ neurons were physiologically functional as shown by the activity of calcium imaging. This study shows that that other tissues besides the postnatal bowel harbor neural crest stem cells or neural progenitors that have the potential to differentiate into functional enteric neurons in vivo and can potentially be used for intestinal nerve regeneration. These DRG-derived neural progenitor cells may be a choice for cell therapy of ENS disease as an allograft. The new knowledge provided by our study is important for the development of neural crest stem cell and cell therapy for the treatment of intestinal neuropathy.

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“…For mesenchymal differentiation, ciNCCs were cultured for 3 weeks in -MEM containing 10% FBS, as previously described (57). The differentiation potential of ciNCC-derived mesenchymal stem cells was achieved by incubation with adipogenesis medium, osteogenesis medium, and chondrogenesis medium, respectively (Cyagen Biosciences).…”

Section: Cincc Differentiationmentioning

confidence: 99%

Conversion of mouse embryonic fibroblasts into neural crest cells and functional corneal endothelia by defined small molecules

et al. 2021

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Reprogramming of somatic cells into desired functional cell types by small molecules has vast potential for developing cell replacement therapy. Here, we developed a stepwise strategy to generate chemically induced neural crest cells (ciNCCs) and chemically induced corneal endothelial cells (ciCECs) from mouse fibroblasts using defined small molecules. The ciNCCs exhibited typical NCC features and could differentiate into ciCECs using another chemical combination in vitro. The resulting ciCECs showed consistent gene expression profiles and self-renewal capacity to those of primary CECs. Notably, these ciCECs could be cultured for as long as 30 passages and still retain the CEC features in defined medium. Transplantation of these ciCECs into an animal model reversed corneal opacity. Our chemical approach for direct reprogramming of mouse fibroblasts into ciNCCs and ciCECs provides an alternative cell source for regeneration of corneal endothelia and other tissues derived from neural crest.

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Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells

Cited by 18 publications

References 40 publications

Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs

Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs

DRG-Derived Neural Progenitors Differentiate into Functional Enteric Neurons Following Transplantation in the Postnatal Colon

Conversion of mouse embryonic fibroblasts into neural crest cells and functional corneal endothelia by defined small molecules

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