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将新生狨猴睾丸单细胞悬液移植到免疫缺陷小鼠中可导致体外睾丸索新体发生。

Grafting of Neonatal marmoset monkey testicular single-cell suspensions into immunodeficient mice leads to ex situ testicular cord neomorphogenesis.

机构信息

Stem Cell Biology Unit, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.

出版信息

Cells Tissues Organs. 2013;198(3):209-20. doi: 10.1159/000355339. Epub 2013 Nov 2.

Abstract

Single-cell suspensions derived from immature rodent and ungulate testes can reconstitute testicular cords upon grafting into immunodeficient mice. In the present study, neonatal common marmoset monkey (Callithrix jacchus) testes were digested to a single-cell suspension, which was transplanted subcutaneously into immunodeficient mice. After 9 or 18 weeks of incubation, the derivatives of the grafted single-cell suspensions were retrieved and analyzed histologically and immunohistochemically. Three of 4 (75%) neonatal grafts exhibited reconstituted seminiferous cords strongly resembling seminiferous cords of the intact neonatal testis. The cords consisted of Sertoli cells, germ cells and peritubular myoid cells, which was confirmed by immunohistochemical marker analysis. Three-dimensional reconstruction models of the grafts revealed elongated tubules. Some of the tubules were branched, which occurs also in vivo, as we show here for the marmoset monkey. Importantly, no teratoma formation by immature pluripotency factor-expressing germ cells was observed. In summary, the reconstituted testicular cords were almost indistinguishable from the cords formed in situ, thereby impressively demonstrating a very high reconstructive potential of a single-cell suspension obtained from the neonatal marmoset monkey testis. To our knowledge, this is the first study demonstrating testicular cord neomorphogenesis for a primate species ex situ.

摘要

从未成熟的啮齿动物和有蹄动物睾丸中分离得到的单细胞悬液,在移植到免疫缺陷小鼠中后可以重新构成睾丸索。在本研究中,新生普通狨猴(Callithrix jacchus)睾丸被消化成单细胞悬液,然后皮下移植到免疫缺陷小鼠中。孵育 9 或 18 周后,取回移植的单细胞悬液的衍生物,并进行组织学和免疫组织化学分析。在 4 个(75%)新生移植中,有 3 个显示出重新构成的类似于完整新生睾丸的生精索。这些索由支持细胞、生殖细胞和小管周围肌样细胞组成,这通过免疫组织化学标志物分析得到了证实。移植的三维重建模型显示出细长的小管。一些小管是分支的,这也发生在体内,正如我们在这里为狨猴展示的那样。重要的是,没有观察到表达不成熟多能性因子的生殖细胞形成畸胎瘤。总之,重新构成的睾丸索几乎与原位形成的索无法区分,从而令人印象深刻地证明了从新生狨猴睾丸中获得的单细胞悬液具有非常高的重建潜力。据我们所知,这是首次证明灵长类动物体外睾丸索新生的研究。

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