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Theranostics 2020; 10(19):8705-8720. doi:10.7150/thno.46854 This issue Cite

Research Paper

Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model

Kai Xia1,2*, Hong Chen2*, Jiancheng Wang2,8*, Xin Feng1,2*, Yong Gao3, Yi Wang2, Rongda Deng1, Chunxing Wu7, Peng Luo1, Min Zhang1,2, Chao Wang2, Yong Zhang7, Yadong Zhang1, Guihua Liu4, Xiang'an Tu1, Xiangzhou Sun1, Weiqiang Li2,3, Qiong Ke2✉, Chunhua Deng1,5✉, Andy Peng Xiang2,6✉

1. Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
2. Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
3. Reproductive Medicine Center, The Key Laboratory for Reproductive Medicine of Guangdong Province, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
4. Center for Reproductive Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
5. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
6. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
7. Department of Nuclear Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
8. Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
*These authors made equal contributions to this work.

✉ Corresponding authors: Andy Peng Xiang (E-mail: xiangpsysu.edu.cn), Chunhua Deng (E-mail: dch0313com) and Qiong Ke (E-mail: kqbearcom).

Citation:
Xia K, Chen H, Wang J, Feng X, Gao Y, Wang Y, Deng R, Wu C, Luo P, Zhang M, Wang C, Zhang Y, Zhang Y, Liu G, Tu X, Sun X, Li W, Ke Q, Deng C, Xiang AP. Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model. Theranostics 2020; 10(19):8705-8720. doi:10.7150/thno.46854. https://www.thno.org/v10p8705.htm
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Abstract

Graphic abstract

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.

Keywords: Stem Leydig cell, Autologous, Transplantation, Testosterone deficiency, Non-human primate

Citation styles

APA
Xia, K., Chen, H., Wang, J., Feng, X., Gao, Y., Wang, Y., Deng, R., Wu, C., Luo, P., Zhang, M., Wang, C., Zhang, Y., Zhang, Y., Liu, G., Tu, X., Sun, X., Li, W., Ke, Q., Deng, C., Xiang, A.P. (2020). Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model. Theranostics, 10(19), 8705-8720. https://doi.org/10.7150/thno.46854.

ACS
Xia, K.; Chen, H.; Wang, J.; Feng, X.; Gao, Y.; Wang, Y.; Deng, R.; Wu, C.; Luo, P.; Zhang, M.; Wang, C.; Zhang, Y.; Zhang, Y.; Liu, G.; Tu, X.; Sun, X.; Li, W.; Ke, Q.; Deng, C.; Xiang, A.P. Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model. Theranostics 2020, 10 (19), 8705-8720. DOI: 10.7150/thno.46854.

NLM
Xia K, Chen H, Wang J, Feng X, Gao Y, Wang Y, Deng R, Wu C, Luo P, Zhang M, Wang C, Zhang Y, Zhang Y, Liu G, Tu X, Sun X, Li W, Ke Q, Deng C, Xiang AP. Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model. Theranostics 2020; 10(19):8705-8720. doi:10.7150/thno.46854. https://www.thno.org/v10p8705.htm

CSE
Xia K, Chen H, Wang J, Feng X, Gao Y, Wang Y, Deng R, Wu C, Luo P, Zhang M, Wang C, Zhang Y, Zhang Y, Liu G, Tu X, Sun X, Li W, Ke Q, Deng C, Xiang AP. 2020. Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model. Theranostics. 10(19):8705-8720.

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