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睾丸生殖细胞的体外培养:调控因子与局限性

In vitro culture of testicular germ cells: regulatory factors and limitations.

作者信息

Huleihel Mahmoud, Abuelhija Mahmoud, Lunenfeld Eitan

机构信息

The Shraga Segal Department of Microbiology and Immunology, Soroka University Medical Center, Beer-Sheva, Israel.

出版信息

Growth Factors. 2007 Aug;25(4):236-52. doi: 10.1080/08977190701783400.

DOI:10.1080/08977190701783400
PMID:18092232
Abstract

Spermatogenesis is regulated mainly by endocrine factors and also by testicular paracrine/autocrine growth factors. These factors are produced by Sertoli cells, germ cells, peritubular cells and interstitial cells, mainly Leydig cells and macrophages. The interactions and the ratio between Sertoli and germ cells in the seminiferous tubules ensure successful spermatogenesis. In order to culture spermatogonial stem cells (SSCs) in vitro, researchers tried to overcome some of the obstacles -- such as the low number of stem cells in the testis, absence of specific markers to identify SSCs -- in addition to difficulties in keeping the SSCs alive in culture. Recently, some growth factors important for the proliferation and differentiation of SSCs were identified, such as glial cell line derived neurotrophic factor (GDNF), stem cell factor (SCF) and leukemia inhibitory factor (LIF); also, markers for SSCs at different stages were reported. Therefore, some groups succeeded in culturing SSCs (under limitations), or more differentiated cells and even were able to produce in vitro germ cells from embryonic stem cells. Thus, success in culturing SSCs is dependent on understanding the molecular mechanisms behind self-renewal and differentiation. Culture of SSCs should be a good tool for discovering new therapeutic avenue for some infertile men or for patients undergoing chemotherapy/radiotherapy (pre-puberty or post-puberty).

摘要

精子发生主要受内分泌因素调节,也受睾丸旁分泌/自分泌生长因子调节。这些因子由支持细胞、生殖细胞、睾丸周细胞和间质细胞产生,主要是睾丸间质细胞和巨噬细胞。生精小管中支持细胞与生殖细胞之间的相互作用及比例确保了精子发生的成功。为了在体外培养精原干细胞(SSCs),研究人员试图克服一些障碍,如睾丸中干细胞数量少、缺乏识别SSCs的特异性标志物,以及在培养中维持SSCs存活的困难。最近,一些对SSCs增殖和分化重要的生长因子被确定,如胶质细胞源性神经营养因子(GDNF)、干细胞因子(SCF)和白血病抑制因子(LIF);同时,不同阶段SSCs的标志物也有报道。因此,一些研究小组成功地(在一定限制下)培养了SSCs,或培养出了更分化的细胞,甚至能够从胚胎干细胞中体外产生生殖细胞。因此,成功培养SSCs取决于对自我更新和分化背后分子机制的理解。SSCs培养应该是为一些不育男性或接受化疗/放疗(青春期前或青春期后)的患者发现新治疗途径的良好工具。

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