Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells |
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| Institution: | 1. 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;2. Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China;3. Key Laboratory of Reproductive Medicine of Guangdong Province, Guangzhou, Guangdong, PR China;4. Department of Blood Transfusion, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, PR China;5. Department of Cell Biology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China;6. Center for Reproductive Medicine, Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China;7. Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, PR China;8. Center for Neurobiology, Zhongshan School of Medicine, Sun-Yat Sen University, Guangzhou, Guangdong, PR China;9. Department of Anatomy and Neurobiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong, PR China;10. Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, PR China;1. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan;2. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;3. Department of Biotechnology, Asia University, Taichung, Taiwan;4. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan;5. Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan;6. Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan;7. Taiji Fetal Medicine Center, Taipei, Taiwan;8. Gene Biodesign Co. Ltd., Taipei, Taiwan;9. Department of Bioengineering, Tatung University, Taipei, Taiwan;1. The Dutch Craniofacial Center, Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Sophia Children''s Hospital Rotterdam, Rotterdam, The Netherlands;2. Department of Plastic and Oral Surgery, (Head of department: Bonnie L. Padwa, DMD, MD), Boston Children''s Hospital, Boston, United States;3. The Craniofacial Unit, Great Ormond Street Hospital, London, United Kingdom;1. The Dutch Craniofacial Center, Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Sophia''s Children''s Hospital Rotterdam, ‘s Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands;2. The Craniofacial Unit, Great Ormond Street Hospital, 30 Guilford Street, London, WC1N1EH, United Kingdom;3. The Craniofacial Centre, Boston Children''s Hospital, 300 Longwood Avenue, Hunnewell Building, Boston, MA, 02115, United States;1. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People''s Hospital, Shanghai JiaoTong University School of Medicine, People''s Republic of China;2. Bio-X Institute of Shanghai JiaoTong University, People''s Republic of China |
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| 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. |
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| Keywords: | Neural crest stem cells Embryonic stem cells Differentiation Non-human primates |
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