title: Overexpression of tropomyosin receptor kinase A improves the survival and Schwann-like cell differentiation of bone marrow stromal cells in nerve grafts for bridging rat sciatic nerve defects.
abstract: Bone marrow stromal cells (BMSCs) can differentiate into Schwann-like cells in vivo and effectively promote nerve regeneration and functional recovery as the seed cells for peripheral nerve repair. However, the survival rate and neural differentiation rate of the transplanted BMSCs are very low, which would limit their efficacy.
  
  
  
  In this work, rat BMSCs were infected by recombinant lentiviruses to construct tropomyosin receptor kinase A (TrkA)-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then used in transplantation for rat sciatic nerve defects.
  
  
  
  We showed that lentivirus-mediated overexpression of TrkA in BMSCs can promote cell survival and protect against serum-starve-induced apoptosis in vitro. At 8 weeks after transplantation, the Schwann-like differentiated ratio of the existing implanted cells had reached 74.8 ± 1.6% in TrkA-overexpressing BMSCs-laden nerve grafts, while 40.7 ± 2.3% and 42.3 ± 1.5% in vector and control BMSCs-laden nerve grafts, but only 8.2 ± 1.8% in TrkA-shRNA-expressing BMSCs-laden nerve grafts. The cell apoptosis ratio of the existing implanted cells in TrkA-overexpressing BMSCs-laden nerve grafts was 16.5 ± 1.2%, while 33.9 ± 1.9% and 42.6 ± 2.9% in vector and control BMSCs-laden nerve grafts, but 87.2 ± 2.5% in TrkA-shRNA-expressing BMSCs-laden nerve grafts.
  
  
  
  These results demonstrate that TrkA overexpression can improve the survival and Schwann-like cell differentiation of BMSCs and prevent cell death in nerve grafts, which may have potential implication in advancing cell transplantation for peripheral nerve repair.
authors: Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China.
authors: Meige
authors: M
authors: Zheng
authors: School of Medicine, Shenzhen University, Shenzhen, China.
authors: Junxiu
authors: J
authors: Duan
authors: School of Medicine, Shenzhen University, Shenzhen, China.
authors: Zhendan
authors: Z
authors: He
authors: Department of Neurology, Shenzhen Shekou People's Hospital, Shenzhen, China.
authors: Zhiwei
authors: Z
authors: Wang
authors: Psychology & Social College, Shenzhen University, Shenzhen, China.
authors: Shuhua
authors: S
authors: Mu
authors: School of Medicine, Shenzhen University, Shenzhen, China.
authors: Zhiwen
authors: Z
authors: Zeng
authors: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China.
authors: Junle
authors: J
authors: Qu
authors: School of Medicine, Shenzhen University, Shenzhen, China. Electronic address: jzhanghappy@163.com.
authors: Jian
authors: J
authors: Zhang
authors: Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, China. Electronic address: david74429@126.com.
authors: Dong
authors: D
authors: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D012584:Sciatic Nerve / Q000473:pathology / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020917:Receptor, trkA
keywords: BMSCs; Schwann-like cell differentiation; TrkA overexpression; nerve transplantation; shRNA interfere; survival