Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.
Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.
J Cell Mol Med. 2020 Apr;24(8):4633-4645. doi: 10.1111/jcmm.15128. Epub 2020 Mar 17.
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.
干细胞移植是治疗莱迪希细胞功能障碍相关疾病的候选方法。然而，仍有许多限制其临床应用的问题。在这里，我们报告了 CXCR4-SF1 双功能脂肪来源干细胞（CXCR4-SF1-ADSCs）的建立及其对莱迪希细胞功能障碍的修复作用。通过流式细胞术（FACS）从脂肪组织中分离出 CD29 CD44 CD34 CD45 ADSCs 并进行纯化。应用携带 CXCR4 和 SF1 基因的慢病毒感染来构建 CXCR4-SF1-ADSCs。CXCR4-SF1-ADSCs 表现出增强的迁移能力，并具有体外分化为莱迪希样细胞的能力。此外，通过尾静脉将双功能 ADSCs 注射到 BPA 介导的莱迪希细胞损伤模型小鼠中。我们发现 CXCR4-SF1-ADSCs 能够归巢到受损的睾丸，分化为莱迪希样细胞，并修复莱迪希细胞功能障碍引起的生殖功能缺陷。此外，我们研究了 SF1 介导的莱迪希细胞分化和睾酮合成的机制，提出 B-box 和 SPRY 结构域包含蛋白（BSPRY）基因参与这一过程。这项研究为治疗莱迪希细胞功能障碍相关疾病提供了新的思路。
