VEGF-Mediated Proliferation of Human Adipose Tissue-Derived Stem Cells

Guangfeng Chen,Cizhong Jiang,Xiangyi Wen,Ming Ying,Qing Zhou,Qionglan Yuan,Yan Zhang,Jieping Zhang,Min Li,Jun Huang,Jianwei Lu,Xiujuan Shi,Xiaoqing Liu,Yushan Zhang,Chen Sun,Chen Zhang,Yun-Yun Xue ,Guo‐Tong Xu ,Shao Nian Yang ,Lixia Lü ,Zi‐Bing Jin ,Yue Qiu

doi:10.1371/journal.pone.0073673

Abstract

Human adipose tissue-derived stem cells (ADSCs) are an attractive multipotent stem cell source with therapeutic applicability across diverse fields for the repair and regeneration of acute and chronically damaged tissues. In recent years, there has been increasing interest in ADSC for tissue engineering applications. However, the mechanisms underlying the regulation of ADSC proliferation are not fully understood. Here we show that 47 transcripts are up-regulated while 23 are down-regulated in ADSC compared to terminally differentiated cells based on global mRNA profiling and microRNA profiling. Among the up-regulated genes, the expression of vascular endothelial growth factor (VEGF) is fine-tuned by miR-199a-5p. Further investigation indicates that VEGF accelerates ADSC proliferation whereas the multipotency of ADSC remains stable in terms of adipogenic, chondrogenic and osteogenic potentials after VEGF treatment, suggesting that VEGF may serve as an excellent supplement for accelerating ADSC proliferation during in vitro expansion.

Highlights

Stem cells are characterized by their ability to undergo selfrenewal and multilineage differentiation and form terminally differentiated cells [1]
Clustering analysis revealed a set of genes sharing a highly similar level of expression between human endothelial and fibroblast cells, whereas adipose tissue stem cells (ADSCs) had a significantly different expression profile compared to human endothelial and fibroblast cells (Fig. 1A)
Further bioinformatics analysis predicted that 47 transcripts were up-regulated while 23 transcripts were down-regulated in ADSC compared to terminally differentiated cells if the intersection of transcripts and miR-predicted targets was applied

Summary

Introduction

Stem cells are characterized by their ability to undergo selfrenewal and multilineage differentiation and form terminally differentiated cells [1]. Bone marrow derived MSCs are promising tools for basic research and regenerative medicine [5]; their isolation is an invasive and painful procedure that often results in a relatively low yield [6]. Similar proliferation rates and gene expression pathways for MSCs and ADSCs have been documented in terms of osteogenic, chondrogenic, adipogenic and neurogenic potentials [13,14,15]. In addition to their multipotency, ADSCs can be isolated from readily available white adipose tissues [6,16]. Due to the combination of these beneficial properties, ADSC research has gained more and more attention over the past decades, with particular focus on tissue engineering and regenerative medicine

Methods

Results

Conclusion