Thrombospondin-1 modified bone marrow mesenchymal stem cells (BMSCs) promote neurite outgrowth and functional recovery in rats with spinal cord injury

Abstract

// Yujie Pu 1 , Ke Meng 1 , Chuanlong Gu 1 , Linlin Wang 1 and Xiaoming Zhang 1 1 Department of Basic Medicine Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, China Correspondence to: Linlin Wang, email: wanglinlin@zju.edu.cn Xiaoming Zhang, email: zxm@zju.edu.cn Keywords: spinal cord injury; bone marrow mesenchymal stem cells (BMSCs); thrombospondin-1 (TSP-1); neurite outgrowth; functional recovery Received: July 25, 2017     Accepted: September 23, 2017     Published: October 24, 2017 ABSTRACT Stem cell therapies are currently gaining momentum in the treatment of spinal cord injury (SCI). However, unsatisfied intrinsic neurite growth capacity constitutes significant obstacles for injured spinal cord repair and ultimately results in neurological dysfunction. The present study assessed the efficacy of thrombospondin-1 (TSP-1), a neurite outgrowth-promoting molecule, modified bone marrow mesenchymal stem cells (BMSCs) on promoting neurite outgrowth in vitro and in vivo of Oxygen–Glucose Deprivation (OGD) treated motor neurons and SCI rat models. The present results demonstrated that the treatment of BMSCs+TSP-1 could promote the neurite length, neuronal survival, and functional recovery after SCI. Additionally, TSP-1 could activate transforming growth factor-β1 (TGF-β1) then induced the smad2 phosphorylation, and expedited the expression of GAP-43 to promote neurite outgrowth. The present study for the first time demonstrated that BMSCs+TSP-1 could promote neurite outgrowth and functional recovery after SCI partly through the TGF-β1/p-Samd2 pathway. The study provided a novel encouraging evidence for the potential treatment of BMSCs modification with TSP-1 in patients with SCI.