Therapeutic Effects and Repair Mechanism of HGF Gene-Transfected Mesenchymal Stem Cells on Injured Endometrium
Xuan Xu, Qiong Xing, Ruijun Liu, Dong Liu, Zhen Yu, Ying Wang, Ping Zhou, Ying V. Zhang, Jianye Wang, Yunxia Cao, Zhaolian Wei
Abstract
There are many studies on the advantages of using mesenchymal stem cells (MSCs) that secrete various paracrine factors for repairing endometrial injury. However, the stability and effectiveness of MSCs require improvement to become a viable therapy. Hepatocyte growth factor (HGF), one of the cytokines secreted by MSCs, promotes vascular repair and mesenchymal to epithelial transformation (MET). Therefore, HGF likely promotes the repair process of the endometrium. We prepared MSCs transfected with the HGF gene to explore its repair effects and mechanism using a damaged endometrium mouse model. HGF gene-transfected MSCs were prepared by electroporation. The transfected MSCs retained their cellular characteristics and significantly increased the expression of HGF ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>P</a:mi> <a:mo><</a:mo> <a:mn>0.01</a:mn> </a:math> ). HGF gene-transfected MSCs helped damaged endometrium to recover its morphological characteristics, improved proliferation and decreased apoptosis of endometrial cells, increased the expression of endometrial vascular growth-related factors, and activated phosphorylated c-Met and AKT in the mouse endometrial damage model ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo><</c:mo> <c:mn>0.05</c:mn> </c:math> ). Compared with normal MSCs, HGF gene-transfected MSCs produced a more significant effect on damaged endometrial epithelium repair by activating the HGF/c-Met and downstream signaling pathways. Our results indicate that HGF gene-transfected MSCs provide an effective and promising tool for injured endometrium therapy.