CXCR4-SF1 bifunctional adipose-derived stem cells benefit for the treatment of Leydig cell dysfunction-related diseases

CXCR4-SF1双功能脂肪来源干细胞对治疗睾丸间质细胞功能障碍相关疾病有益

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作者:Xue Li,Ao Xu,Kai Li,Jie Zhang,Qin Li,Gang Zhao,Yue Zhang,Hang Yuan,Yafei Guo,Ping Lin,Lugang Huang

Abstract

Stem cell transplantation is a candidate method for the treatment of Leydig cell dysfunction-related diseases. However, there are still many problems that limit its clinical application. Here, we report the establishment of CXCR4-SF1 bifunctional adipose-derived stem cells (CXCR4-SF1-ADSCs) and their reparative effect on Leydig cell dysfunction. CD29+ CD44+ CD34- CD45- ADSCs were isolated from adipose tissue and purified by fluorescence-activated cell sorting (FACS). Infection with lentiviruses carrying the CXCR4 and SF1 genes was applied to construct CXCR4-SF1-ADSCs. The CXCR4-SF1-ADSCs exhibited enhanced migration and had the ability to differentiate into Leydig-like cells in vitro. Furthermore, the bifunctional ADSCs were injected into BPA-mediated Leydig cell damage model mice via the tail vein. We found that the CXCR4-SF1-ADSCs were capable of homing to the injured testes, differentiating into Leydig-like cells and repairing the deficiency in reproductive function caused by Leydig cell dysfunction. Moreover, we investigated the mechanism underlying SF1-mediated differentiation and testosterone synthesis in Leydig cells, and the B-box and SPRY Domain Containing Protein (BSPRY) gene was proposed to be involved in this process. This study provides insight into the treatment of Leydig cell dysfunction-related diseases.

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