Fate of bone marrow stem cells transplanted into the testis - Potential implication for men with testicular failure

Fate of bone marrow stem cells transplanted into the testis - Potential implication for men with testicular failure
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DOI:
10.2353/ajpath.2007.060543
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发表时间:
2007-03-01
影响因子:
6
通讯作者:
Swerdloff, Ronald S.
Swerdloff, Ronald S.
中科院分区:
医学2区
文献类型:
--
作者:
Lue, YanHe;Erkkila, Krista;Swerdloff, Ronald S.

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为了评估睾丸中成体干细胞的分化,我们将成年绿色荧光蛋白(GFP)转基因小鼠的骨髓细胞注射到白消安处理的野生型或c-kit突变(W/W-v)小鼠的曲细精管和睾丸中。移植后10至12周,我们检查了移植的骨髓细胞的命运,发现它们在受体睾丸中存活。在白消安处理的小鼠和W/W-v小鼠中,一些GFP阳性供体细胞具有支持细胞外观,并在生精小管内表达促卵泡激素受体。此外,在受体睾丸的睾丸中发现GFP阳性供体细胞,并且它们表达细胞色素P450侧链裂解酶(P450 SCC)。在白消安处理小鼠的曲细精管中,GEP阳性供体细胞具有精原细胞或精母细胞的外观,并表达VASA。然而,这在W/W-v小鼠的曲细精管中未发现。我们的结论是,成人骨髓细胞,在一个良好的睾丸环境,分化成体细胞和生殖细胞系。受体睾丸中的邻近细胞可以控制适当部位的干细胞分化。这一临床相关的发现提高了通过干细胞治疗男性不育和睾酮缺乏症的可能性。
To assess adult stem cell differentiation in the testis, we injected bone marrow cells from adult green fluorescent protein (GFP) transgenic mice into the seminiferous tubules and the testicular interstitium of busulfan-treated wild-type or c-kit mutant (W/W-v) mice. Ten to 12 weeks after transplantation, we examined the fate of the transplanted bone marrow cells and found that they survived in recipient testes. in both the busulfan-treated and W/W-v mice, some of the GFP-positive donor cells had a Sertoli cell appearance and expressed follicle-stimulating hormone receptor within the seminiferous tubules. in addition, GFP-positive donor cells were found in the interstitium of recipient testes, and they expressed the cytochrome P450 side chain cleavage enzyme (P450scc). In the seminiferous tubules of busulfan-treated mice, GEP-positive donor cells had the appearance of spermatogonia or spermatocytes and expressed VASA. However, this was not found in the seminiferous tubules of W/W-v mice. We conclude that adult bone marrow cells, in a favorable testicular environment, differentiate into somatic and germ cell lineages. The resident neighboring cells in the recipient testis may control site-appropriate stem cell differentiation. This clinically relevant finding raises the possibility for treatment of male infertility and testosterone deficiency through the therapeutic use of stem cells.