PMID- 27497699 OWN - NLM STAT- MEDLINE DCOM- 20170718 LR - 20181202 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 18 IP - 10 DP - 2016 Oct TI - 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. PG - 1256-69 LID - S1465-3249(16)30449-2 [pii] LID - 10.1016/j.jcyt.2016.06.015 [doi] AB - BACKGROUND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - Copyright (c) 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Zheng, Meige AU - Zheng M AD - 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. FAU - Duan, Junxiu AU - Duan J AD - School of Medicine, Shenzhen University, Shenzhen, China. FAU - He, Zhendan AU - He Z AD - School of Medicine, Shenzhen University, Shenzhen, China. FAU - Wang, Zhiwei AU - Wang Z AD - Department of Neurology, Shenzhen Shekou People's Hospital, Shenzhen, China. FAU - Mu, Shuhua AU - Mu S AD - Psychology & Social College, Shenzhen University, Shenzhen, China. FAU - Zeng, Zhiwen AU - Zeng Z AD - School of Medicine, Shenzhen University, Shenzhen, China. FAU - Qu, Junle AU - Qu J AD - Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China. FAU - Zhang, Jian AU - Zhang J AD - School of Medicine, Shenzhen University, Shenzhen, China. Electronic address: jzhanghappy@163.com. FAU - Wang, Dong AU - Wang D AD - 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. LA - eng PT - Journal Article DEP - 20160803 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - EC 2.7.10.1 (Receptor, trkA) SB - IM MH - Animals MH - Bone Marrow Cells/*physiology MH - Cell Differentiation/*genetics MH - Cell Survival/genetics MH - Cells, Cultured MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*physiology MH - Nerve Regeneration/*genetics MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkA/*genetics/metabolism MH - Schwann Cells/cytology/*physiology MH - Sciatic Nerve/pathology/*physiology MH - Up-Regulation/genetics OTO - NOTNLM OT - BMSCs OT - Schwann-like cell differentiation OT - TrkA overexpression OT - nerve transplantation OT - shRNA interfere OT - survival EDAT- 2016/08/09 06:00 MHDA- 2017/07/19 06:00 CRDT- 2016/08/08 06:00 PHST- 2016/05/24 00:00 [received] PHST- 2016/06/28 00:00 [accepted] PHST- 2016/08/08 06:00 [entrez] PHST- 2016/08/09 06:00 [pubmed] PHST- 2017/07/19 06:00 [medline] AID - S1465-3249(16)30449-2 [pii] AID - 10.1016/j.jcyt.2016.06.015 [doi] PST - ppublish SO - Cytotherapy. 2016 Oct;18(10):1256-69. doi: 10.1016/j.jcyt.2016.06.015. Epub 2016 Aug 3.