Effects on Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells Engineered to Express Neurotrophic Factors.

Yi Wang,Xiaoyan Cui,Youguo Ying

doi:10.1155/2016/1801340

Abstract

Mesenchymal stem cells (MSCs) are multipotential cells with capability to form colonies in vitro and differentiate into distinctive end-stage cell types. Although MSCs secrete many cytokines, the efficacy can be improved through combination with neurotrophic factors (NTFs). Moreover, MSCs are excellent opportunities for local delivery of NTFs into injured tissues. The aim of this present study is to evaluate the effects of overexpressing NTFs on proliferation and differentiation of human umbilical cord-derived mesenchymal stem cells (HUMSCs). Overexpressing NTFs had no effect on cell proliferation. Overexpressing NT-3, BDNF, and NGF also had no significant effect on the differentiation of HUMSCs. Overexpressing NTFs all promoted the neurite outgrowth of embryonic chick E9 dorsal root ganglion (DRG). The gene expression profiles of the control and NT-3- and BDNF-modified HUMSCs were compared using RNA sequencing and biological processes and activities were revealed. This study provides novel information about the effects of overexpressing NTFs on HUMSCs and insight into the choice of optimal NTFs for combined cell and gene therapy.

Highlights

Mesenchymal stem cells (MSCs) are multipotential cells with capability to form colonies in vitro and differentiate into distinctive end-stage cell types, such as adipocytes, osteoblasts, and chondrocytes, as well as other connective tissues and neuronal cells [1,2,3,4]
After transduction of Human umbilical cord-derived mesenchymal stem cells (HUMSCs) with NT3, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) lentivirus, we confirmed that production and secretion of these neurotrophic factors (NTFs) were increased in HUMSCs
In HUMSCs transduced with the respective NTFs using western blots, the protein of each of neurotrophin 3 (NT-3) and GDNF was significantly increased and the protein of each of BDNF and NGF was slightly increased (Figures 2(c) and 2(d))

Summary

Introduction

Mesenchymal stem cells (MSCs) are multipotential cells with capability to form colonies in vitro and differentiate into distinctive end-stage cell types, such as adipocytes, osteoblasts, and chondrocytes, as well as other connective tissues and neuronal cells [1,2,3,4]. They are a heterogeneous population and can be isolated from several tissues, including bone marrow, adipose, umbilical cord blood, umbilical cord, and amnion. They can migrate and secrete a variety of cytokines in an injury environment, including insulin-like growth factor (IGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), granulocytemacrophage colony stimulating factor (GM-CSF), fibroblast growth factor- (FGF-) 2, and transforming growth factor (TGF) [8]

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