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人类精原干细胞在小鼠睾丸中的长期存活

Long-term survival of human spermatogonial stem cells in mouse testes.

作者信息

Nagano Makoto, Patrizio Pasquale, Brinster Ralph L

机构信息

Department of Animal Biology, School of Veterinary Medicine., University of Pennsylvania, Philadelphia, Pennsylvania 19104-6009, USA.

出版信息

Fertil Steril. 2002 Dec;78(6):1225-33. doi: 10.1016/s0015-0282(02)04345-5.

DOI:10.1016/s0015-0282(02)04345-5
PMID:12477516
Abstract

OBJECTIVE

To evaluate colonizing ability of human spermatogonial stem cells in mouse testes.

DESIGN

Transplantation of human testis cells into the seminiferous tubules of immunodeficient mice.

SETTING

University hospital and academic laboratory.

PATIENT(S): Men with obstructive azoospermia or maturation arrest of spermatogenesis. Analyzed up to 6 months after transplantation. Also analyzed: cryopreservation of donor cells, donor cell concentrations, and leuprolide treatment of recipients.

MAIN OUTCOME MEASURE(S): Detection of human donor cells in recipient testes using whole-mount immunohistochemistry with antibodies that react with human germ cells.

RESULT(S): Mouse testes were colonized by human testis cells obtained from each of 6 patients; overall, human spermatogonia were found in 16 of 22 (73%) recipient testes. Human spermatogonial stem cells survived in mouse testes for at least 6 months and proliferated during the first month after transplantation. No human-differentiating spermatogonia were identified, and meiotic differentiation did not occur in mouse testes. In this initial study, human stem cell colonization was not influenced by cryopreservation of donor cells, donor cell concentration, or leuprolide treatment of recipient mice.

CONCLUSION(S): Xenogeneic transplantation of human germ cells using mice as recipients is feasible and could be used as a biological assay system to further characterize human spermatogonial stem cells. This study might provide a mechanism to evaluate the status of the stem cell population in selected infertile male patients.

摘要

目的

评估人类精原干细胞在小鼠睾丸中的定殖能力。

设计

将人类睾丸细胞移植到免疫缺陷小鼠的生精小管中。

地点

大学医院和学术实验室。

患者

梗阻性无精子症或精子发生成熟停滞的男性。移植后长达6个月进行分析。还分析了:供体细胞的冷冻保存、供体细胞浓度以及受体的亮丙瑞林治疗。

主要观察指标

使用与人类生殖细胞反应的抗体进行全组织免疫组化检测受体睾丸中的人类供体细胞。

结果

来自6名患者的人类睾丸细胞定殖于小鼠睾丸;总体而言,在22只受体睾丸中的16只(73%)中发现了人类精原细胞。人类精原干细胞在小鼠睾丸中存活至少6个月,并在移植后的第一个月增殖。未鉴定出人类分化型精原细胞,且小鼠睾丸中未发生减数分裂分化。在这项初步研究中,人类干细胞定殖不受供体细胞的冷冻保存、供体细胞浓度或受体小鼠的亮丙瑞林治疗的影响。

结论

以小鼠为受体进行人类生殖细胞的异种移植是可行的,可作为一种生物学检测系统来进一步表征人类精原干细胞。本研究可能提供一种机制来评估特定不育男性患者的干细胞群体状态。

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