title: Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection.
abstract: BACKGROUND
  Severe spinal cord injury often causes temporary or permanent damages in strength, sensation, or autonomic functions below the site of the injury. So far, there is still no effective treatment for spinal cord injury. Mesenchymal stem cells (MSCs) have been used to repair injured spinal cord as an effective strategy. However, the low neural differentiation frequency of MSCs has limited its application. The present study attempted to explore whether the grafted MSC-derived neural-like cells in a gelatin sponge (GS) scaffold could maintain neural features or transdifferentiate into myelin-forming cells in the transected spinal cord.
  
  
  METHODS
  We constructed an engineered tissue by co-seeding of MSCs with genetically enhanced expression of neurotrophin-3 (NT-3) and its high-affinity receptor tropomyosin receptor kinase C (TrkC) separately into a three-dimensional GS scaffold to promote the MSCs differentiating into neural-like cells and transplanted it into the gap of a completely transected rat spinal cord. The rats received extensive post-operation care, including cyclosporin A administrated once daily for 2 months.
  
  
  RESULTS
  MSCs modified genetically could differentiate into neural-like cells in the MN + MT (NT-3-MSCs + TrKC-MSCs) group 14 days after culture in the GS scaffold. However, after the MSC-derived neural-like cells were transplanted into the injury site of spinal cord, some of them appeared to lose the neural phenotypes and instead transdifferentiated into myelin-forming cells at 8 weeks. In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons. And the injured host neurons were rescued, and axon regeneration was induced by grafted MSCs modified genetically. In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups.
  
  
  CONCLUSIONS
  Grafted MSC-derived neural-like cells in the GS scaffold can transdifferentiate into myelin-forming cells in the completely transected rat spinal cord.
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. qiuxuecheng1990@163.com.
authors.forename: Xue-Cheng
authors.initials: XC
authors.lastname: Qiu
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. 821512179@qq.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. rongyiz@126.com.
authors.forename: Rong-Yi
authors.initials: RY
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. dingying@mail.sysu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. xiangzeng83@gmail.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. laibiqin@126.com.
authors.forename: Bi-Qin
authors.initials: BQ
authors.lastname: Lai
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. eng_ang_ling@nuhs.edu.sg.
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.affiliation: Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. wujl@mail.sysu.edu.cn.
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. zengysh@mail.sysu.edu.cn.|Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. zengysh@mail.sysu.edu.cn.|Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China. zengysh@mail.sysu.edu.cn.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. zengysh@mail.sysu.edu.cn.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001369:Axons / Q000502:physiology*; D001522:Behavior, Animal; D018929:Cell Culture Techniques; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function; D012038:Regeneration; D013119:Spinal Cord Injuries / Q000628:therapy*; D054457:Tissue Scaffolds
chemical_list: D020933:Neurotrophin 3; D020812:Receptor, trkC