SPERMATOGONIAL STEM CELL CULTURE AND TRANSPLANTATION

精原干细胞培养和移植

• 批准号: 6181743
• 负责人: Ralph Lawrence Brinster
• 金额: $ 28.68万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6181743
• 关键词: SCID mouse; athymic mouse; cell transplantation; fertility immunology; male; method development; reproductive tissue transplantation; sperm; spermatogenesis; stem cells; tissue /cell culture; transplantation immunology

We have developed a method that allows transfer of testicular cells from a fertile male to the seminiferous tubules of an infertile male. Following transfer, the donor cell population establishes normal spermatogenesis in the recipient testes, and mature spermatozoa are produced and found in the epididymis. In the most successful transplantations, the recipient male becomes fertile, and the donor cell haplotype if found in progeny of the male. We have used this approach to demonstrate that spermatogonial stem cells can be cryopreserved, thus making individual male germ lines immortal. In addition, transplanted rat testis cells will generate spermatogenesis in the seminiferous tubules of immunodeficient mice and produce rat spermatozoa, suggesting that xenogeneic spermatogenesis may be possible for other species. This testis call transplantation technique provides an opportunity to perform experiments with male germ cells that previously were difficult or impossible. In this project, we have three specific aims. 1. To increase the efficiency with which donor cells colonize and repopulate the seminiferous tubules of recipient mice. 2. To grow in vitro and expand the number of the testicular stem cells responsible for repopulating the recipient testis. 3. To modify the genetic characteristics of spermatogonial stem cells and recover the new haplotype in progeny. The studies proposed will make spermatogonial transplantation useful for a wide range of applications in biology, medicine and agriculture. In addition, the knowledge gained will help alleviate certain forms of male infertility and help in the development of new contraceptive approaches.

我们开发了一种方法，可以将睾丸细胞从 将具有生育能力的男性的生精小管连接到不育男性的生精小管。 移植后，供体细胞群建立正常 受者睾丸中的精子发生和成熟精子 产生并发现于附睾。 在最成功的 移植后，受体男性变得有生育能力，而供体细胞 如果在雄性后代中发现单倍型。 我们已经使用了这个方法 证明精原干细胞可以冷冻保存，从而 使个体雄性生殖系永生。 另外还移植了 大鼠睾丸细胞将在生精细胞中产生精子 免疫缺陷小鼠的肾小管并产生大鼠精子，这表明 异种精子发生对于其他物种来说是可能的。 这 睾丸移植技术提供了执行的机会 以前很难或无法进行的男性生殖细胞实验 不可能的。 在这个项目中，我们有三个具体目标。 1. 至 提高供体细胞定殖和重新增殖的效率 受体小鼠的生精小管。 2. 体外培养 扩大负责睾丸干细胞的数量 重新填充受体睾丸。 3. 改变基因 精原干细胞的特性并恢复新的 后代中的单倍型。 拟议的研究将使精原细胞移植有用 在生物学、医学和农业领域有着广泛的应用。 在 此外，所获得的知识将有助于缓解某些形式的男性 不孕症并帮助开发新的避孕方法。