Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model
Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model
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自体间质干细胞移植在睾酮缺乏的非人灵长类动物模型中的恢复功能
DOI：
10.7150/thno.46854
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发表时间：
2020-07
期刊：
影响因子：
12.4
通讯作者：
Xiang Andy Peng
中科院分区：
文献类型：
--
作者：
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 Xiangan;Sun Xiangzhou;Li Weiqiang;Ke Qiong;Deng Chunhua;Xiang Andy Peng
基本原理：间质干细胞（SLCs）移植可以恢复啮齿动物模型中的睾酮产生，因此是治疗睾酮缺乏症（TD）的潜在解决方案。然而，目前尚不清楚这些有利的影响是否会在更临床相关的大动物模型中重现。因此，我们评估了在睾酮缺乏的非人灵长类动物（NHP）模型中自体SLC移植的可行性、安全性和有效性。方法：采用流式细胞术从老年食蟹猴（> 19岁）睾丸活检组织中分离出食蟹猴SLC（CM-SLC）。将自体CM-SLCs注射到7只猴的睾丸内。另4只猴以同样的方式注射食蟹猴皮肤成纤维细胞（CM-DF）作为对照。然后检查动物的性激素、精液、身体成分、握力和运动活动。结果如下：我们首先分离了CD 271 + CM-SLCs，这些细胞被证实在体外持续扩增并显示出分化为产生睾丸酮的Leydig细胞（LC）的潜力。与CM-DFs移植相比，自体CM-SLCs移植到老年猴体内可显著提高血清睾酮水平，持续8周，而不需要任何免疫抑制剂。重要的是，CM-SLC移植恢复了精子发生并改善了TD相关症状，例如与体脂量，瘦体重，骨矿物质密度，强度和运动能力相关的症状。结论：我们的短期观察首次证明，自体SLC可以增加灵长类动物模型中的睾酮水平并改善相关TD症状。需要一个更大的长期随访队列来评估自体SLC用于TD治疗的转化潜力。
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.
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影响因子：
16.6
作者：
Burwitz BJ;Wu HL;Abdulhaqq S;Shriver-Munsch C;Swanson T;Legasse AW;Hammond KB;Junell SL;Reed JS;Bimber BN;Greene JM;Webb GM;Northrup M;Laub W;Kievit P;MacAllister R;Axthelm MK;Ducore R;Lewis A;Colgin LMA;Hobbs T;Martin LD;Ferguson B;Thomas CR Jr;Panoskaltsis-Mortari A;Meyers G;Stanton JJ;Maziarz RT;Sacha JB
通讯作者：
Sacha JB
DOI：
10.1016/j.jsxm.2016.04.068
发表时间：
2016-07
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Trost LW;Mulhall JP
通讯作者：
Mulhall JP
影响因子：
4.2
作者：
L. O. Underdahl;A. Albert
通讯作者：
L. O. Underdahl;A. Albert
影响因子：
4.3
作者：
Yu S;Zhang P;Dong W;Zeng W;Pan C
通讯作者：
Pan C
影响因子：
--
作者：
Lee S;Choi E;Cha MJ;Hwang KC
通讯作者：
Hwang KC