title: Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells.
abstract: Neural crest stem cells (NCSCs), a population of multipotent cells that migrate extensively and give rise to diverse derivatives, including peripheral and enteric neurons and glia, craniofacial cartilage and bone, melanocytes and smooth muscle, have great potential for regenerative medicine. Non-human primates provide optimal models for the development of stem cell therapies. Here, we describe the first derivation of NCSCs from cynomolgus monkey embryonic stem cells (CmESCs) at the neural rosette stage. CmESC-derived neurospheres replated on polyornithine/laminin-coated dishes migrated onto the substrate and showed characteristic expression of NCSC markers, including Sox10, AP2α, Slug, Nestin, p75, and HNK1. CmNCSCs were capable of propagating in an undifferentiated state in vitro as adherent or suspension cultures, and could be subsequently induced to differentiate towards peripheral nervous system lineages (peripheral sympathetic neurons, sensory neurons, and Schwann cells) and mesenchymal lineages (osteoblasts, adipocytes, chondrocytes, and smooth muscle cells). CmNCSCs transplanted into developing chick embryos or fetal brains of cynomolgus macaques survived, migrated, and differentiated into progeny consistent with a neural crest identity. Our studies demonstrate that CmNCSCs offer a new tool for investigating neural crest development and neural crest-associated human disease and suggest that this non-human primate model may facilitate tissue engineering and regenerative medicine efforts.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Key Laboratory of Reproductive Medicine of Guangdong Province, Guangzhou, Guangdong, PR China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Department of Blood Transfusion, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Wanyi
authors.initials: W
authors.lastname: Lin
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Department of Cell Biology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ke
authors.affiliation: Center for Reproductive Medicine, Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Xingqiang
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Neurobiology, Zhongshan School of Medicine, Sun-Yat Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Department of Anatomy and Neurobiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, PR China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Center for Neurobiology, Zhongshan School of Medicine, Sun-Yat Sen University, Guangzhou, Guangdong, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, PR China. Electronic address: songwu@mail.sysu.edu.cn.
authors.forename: Wu
authors.initials: W
authors.lastname: Song
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China; Key Laboratory of Reproductive Medicine of Guangdong Province, Guangzhou, Guangdong, PR China. Electronic address: xiangp@mail.sysu.edu.cn.
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004594:Electrophysiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
keywords: Differentiation; Embryonic stem cells; Neural crest stem cells; Non-human primates