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Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model
Rationale: Stem Leydig cells (SLCs) transplantation can restore testosterone production in rodent models and is thus a potential solution for treating testosterone deficiency (TD). However, it remains unknown whether these favorable effects will be reproduced in more clinically relevant large-animal...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392013/ https://www.ncbi.nlm.nih.gov/pubmed/32754273 http://dx.doi.org/10.7150/thno.46854 |
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author | Xia, Kai Chen, Hong Wang, Jiancheng Feng, Xin Gao, Yong Wang, Yi Deng, Rongda Wu, Chunxing Luo, Peng Zhang, Min Wang, Chao Zhang, Yong Zhang, Yadong Liu, Guihua Tu, Xiang'an Sun, Xiangzhou Li, Weiqiang Ke, Qiong Deng, Chunhua Xiang, Andy Peng |
author_facet | Xia, Kai Chen, Hong Wang, Jiancheng Feng, Xin Gao, Yong Wang, Yi Deng, Rongda Wu, Chunxing Luo, Peng Zhang, Min Wang, Chao Zhang, Yong Zhang, Yadong Liu, Guihua Tu, Xiang'an Sun, Xiangzhou Li, Weiqiang Ke, Qiong Deng, Chunhua Xiang, Andy Peng |
author_sort | Xia, Kai |
collection | PubMed |
description | Rationale: Stem Leydig cells (SLCs) transplantation can restore testosterone production in rodent models and is thus a potential solution for treating testosterone deficiency (TD). However, it remains unknown whether these favorable effects will be reproduced in more clinically relevant large-animal models. Therefore, we assessed the feasibility, safety and efficacy of autologous SLCs transplantation in a testosterone-deficient non-human primate (NHP) model. Methods: Cynomolgus monkey SLCs (CM-SLCs) were isolated from testis biopsies of elderly (> 19 years) cynomolgus monkeys by flow cytometry. Autologous CM-SLCs were injected into the testicular interstitium of 7 monkeys. Another 4 monkeys were injected the same way with cynomolgus monkey dermal fibroblasts (CM-DFs) as controls. The animals were then examined for sex hormones, semen, body composition, grip strength, and exercise activity. Results: We first isolated CD271(+) CM-SLCs which were confirmed to expand continuously and show potential to differentiate into testosterone-producing Leydig cells (LCs) in vitro. Compared with CM-DFs transplantation, engraftment of autologous CM-SLCs into elderly monkeys could significantly increase the serum testosterone level in a physiological pattern for 8 weeks, without any need for immunosuppression. Importantly, CM-SLCs transplantation recovered spermatogenesis and ameliorated TD-related symptoms, such as those related to body fat mass, lean mass, bone mineral density, strength and exercise capacity. Conclusion: For the first time, our short-term observations demonstrated that autologous SLCs can increase testosterone levels and ameliorate relevant TD symptoms in primate models. A larger cohort with long-term follow-up will be required to assess the translational potential of autologous SLCs for TD therapy. |
format | Online Article Text |
id | pubmed-7392013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-73920132020-08-03 Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model Xia, Kai Chen, Hong Wang, Jiancheng Feng, Xin Gao, Yong Wang, Yi Deng, Rongda Wu, Chunxing Luo, Peng Zhang, Min Wang, Chao Zhang, Yong Zhang, Yadong Liu, Guihua Tu, Xiang'an Sun, Xiangzhou Li, Weiqiang Ke, Qiong Deng, Chunhua Xiang, Andy Peng Theranostics Research Paper Rationale: Stem Leydig cells (SLCs) transplantation can restore testosterone production in rodent models and is thus a potential solution for treating testosterone deficiency (TD). However, it remains unknown whether these favorable effects will be reproduced in more clinically relevant large-animal models. Therefore, we assessed the feasibility, safety and efficacy of autologous SLCs transplantation in a testosterone-deficient non-human primate (NHP) model. Methods: Cynomolgus monkey SLCs (CM-SLCs) were isolated from testis biopsies of elderly (> 19 years) cynomolgus monkeys by flow cytometry. Autologous CM-SLCs were injected into the testicular interstitium of 7 monkeys. Another 4 monkeys were injected the same way with cynomolgus monkey dermal fibroblasts (CM-DFs) as controls. The animals were then examined for sex hormones, semen, body composition, grip strength, and exercise activity. Results: We first isolated CD271(+) CM-SLCs which were confirmed to expand continuously and show potential to differentiate into testosterone-producing Leydig cells (LCs) in vitro. Compared with CM-DFs transplantation, engraftment of autologous CM-SLCs into elderly monkeys could significantly increase the serum testosterone level in a physiological pattern for 8 weeks, without any need for immunosuppression. Importantly, CM-SLCs transplantation recovered spermatogenesis and ameliorated TD-related symptoms, such as those related to body fat mass, lean mass, bone mineral density, strength and exercise capacity. Conclusion: For the first time, our short-term observations demonstrated that autologous SLCs can increase testosterone levels and ameliorate relevant TD symptoms in primate models. A larger cohort with long-term follow-up will be required to assess the translational potential of autologous SLCs for TD therapy. Ivyspring International Publisher 2020-07-09 /pmc/articles/PMC7392013/ /pubmed/32754273 http://dx.doi.org/10.7150/thno.46854 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Xia, Kai Chen, Hong Wang, Jiancheng Feng, Xin Gao, Yong Wang, Yi Deng, Rongda Wu, Chunxing Luo, Peng Zhang, Min Wang, Chao Zhang, Yong Zhang, Yadong Liu, Guihua Tu, Xiang'an Sun, Xiangzhou Li, Weiqiang Ke, Qiong Deng, Chunhua Xiang, Andy Peng Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model |
title | Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model |
title_full | Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model |
title_fullStr | Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model |
title_full_unstemmed | Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model |
title_short | Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model |
title_sort | restorative functions of autologous stem leydig cell transplantation in a testosterone-deficient non-human primate model |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392013/ https://www.ncbi.nlm.nih.gov/pubmed/32754273 http://dx.doi.org/10.7150/thno.46854 |
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