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封装化人睾丸间质细胞样细胞移植:治疗睾酮缺乏的新选择。

Transplantation of encapsulated human Leydig-like cells: A novel option for the treatment of testosterone deficiency.

作者信息

Feng Xin, Xia Kai, Ke Qiong, Deng Rongda, Zhuang Jintao, Wan Zi, Luo Peng, Wang Fulin, Zang Zhijun, Sun Xiangzhou, Xiang Andy Peng, Tu Xiang'an, Gao Yong, Deng Chunhua

机构信息

Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.

Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.

出版信息

Mol Cell Endocrinol. 2021 Jan 1;519:111039. doi: 10.1016/j.mce.2020.111039. Epub 2020 Sep 24.

Abstract

Previous studies have demonstrated that the transplantation of alginate-poly-ʟ-lysine-alginate (APA)-encapsulated rat Leydig cells (LCs) provides a promising approach for treating testosterone deficiency (TD). Nevertheless, LCs have a limited capacity to proliferate, limiting the efficacy of LC transplantation therapy. Here, we established an efficient differentiation system to obtain functional Leydig-like cells (LLCs) from human stem Leydig cells (hSLCs). Then we injected APA-encapsulated LLCs into the abdominal cavities of castrated mice without an immunosuppressor. The APA-encapsulated cells survived and partially restored testosterone production for 90 days in vivo. More importantly, the transplantation of encapsulated LLCs ameliorated the symptoms of TD, such as fat accumulation, muscle atrophy and adipocyte accumulation in bone marrow. Overall, these results suggest that the transplantation of encapsulated LLCs is a promising new method for testosterone supplementation with potential clinical applications in TD.

摘要

先前的研究表明,移植藻酸盐-聚-L-赖氨酸-藻酸盐(APA)包封的大鼠睾丸间质细胞(LCs)为治疗睾酮缺乏症(TD)提供了一种很有前景的方法。然而,LCs的增殖能力有限,限制了LC移植治疗的效果。在此,我们建立了一种高效的分化系统,以从人干细胞睾丸间质细胞(hSLCs)中获得功能性类睾丸间质细胞(LLCs)。然后,我们将APA包封的LLCs注射到未使用免疫抑制剂的去势小鼠腹腔中。APA包封的细胞在体内存活并部分恢复睾酮分泌达90天。更重要的是,移植包封的LLCs改善了TD的症状,如脂肪堆积、肌肉萎缩和骨髓中脂肪细胞堆积。总体而言,这些结果表明,移植包封的LLCs是一种有前景的补充睾酮的新方法,在TD中具有潜在的临床应用价值。

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