Department of Cell Biology, Faculty of Science, Charles University, Viničná 7, Prague 2, 128 00, Czech Republic.
Stem Cell Res Ther. 2024 Nov 13;15(1):421. doi: 10.1186/s13287-024-04050-2.
Regenerative medicine and transplantation science continuously seek methods to circumvent immune-mediated rejection and promote tissue regeneration. Sertoli cells, with their inherent immunoprotective properties, emerge as pivotal players in this quest. However, whether Sertoli cells can play immunomodulatory role in tadpole tail regeneration and can thus benefit the regeneration process are needed to be discovered.
Immature Sertoli cells from Xenopus tropicalis (XtiSCs) were transplanted into X. tropicalis tadpoles, followed by the amputation of the final third of their tails. We assessed the migration of XtiSCs, tail regeneration length, muscle degradation and growth, and macrophage counts across various regions including the entire tail, tail trunk, injection site, and regeneration site. The interactions between XtiSCs and macrophages were examined using a confocal microscope. To deplete macrophages, clodronate liposomes were administered prior to the transplantation of XtiSCs, while the administration of control liposomes acted as a negative control. Student's t-test was used to compare the effects of XtiSCs injection to those of a 2/3PBS injection across groups with no liposomes, control liposomes, and clodronate liposomes.
XtiSCs have excellent viability after transplantation to tadpole tail and remarkable homing capabilities to the regeneration site after tail amputation. XtiSCs injection increased macrophage numbers at 3 days post-amputation and 5 days post-amputation in the tail trunk, specifically at the injection site and at the regenerated tail, in a macrophage depleted environment (clodronate-liposome injection). What's more, XtiSCs injection decreased muscle fibers degradation significantly at 1 day post-amputation and facilitated new muscle growth significantly at 3 days post-amputation. In addition, whole-mount immunostaining showed that some XtiSCs co-localized with macrophages. And we observed potential mitochondria transport from XtiSCs to macrophages using MitoTracker staining in tadpole tail.
Our study delineates the novel role of XtiSCs in facilitating muscle regeneration post tadpole tail amputation, underscoring a unique interaction with macrophages that is crucial for regenerative success. This study not only highlights the therapeutic potential of Sertoli cells in regenerative medicine but also opens avenues for clinical translation, offering insights into immunoregulatory strategies that could enhance tissue regeneration and transplant acceptance.
再生医学和移植科学不断寻求方法来规避免疫介导的排斥反应并促进组织再生。具有固有免疫保护特性的支持细胞成为这一探索中的关键角色。然而，支持细胞是否能在蝌蚪尾巴再生中发挥免疫调节作用，并因此有益于再生过程，这一点仍有待发现。
从非洲爪蟾（Xenopus tropicalis）中分离出未成熟的支持细胞（XtiSCs），并将其移植到非洲爪蟾蝌蚪体内，然后切除其尾巴的最后三分之一。我们评估了 XtiSCs 的迁移、尾巴再生的长度、肌肉降解和生长以及巨噬细胞在整个尾巴、尾巴主干、注射部位和再生部位等不同区域的数量。使用共聚焦显微镜检查 XtiSCs 与巨噬细胞之间的相互作用。在移植 XtiSCs 之前，先用氯膦酸盐脂质体耗竭巨噬细胞，而给予对照脂质体则作为阴性对照。使用学生 t 检验比较无脂质体、对照脂质体和氯膦酸盐脂质体组中 XtiSCs 注射与 2/3PBS 注射的效果。
XtiSCs 在移植到蝌蚪尾巴后具有很好的活力，在尾巴切除后具有显著的归巢能力到达再生部位。在巨噬细胞耗竭的环境（氯膦酸盐脂质体注射）中，XtiSCs 注射在尾巴切除后 3 天和 5 天增加了尾巴主干中的巨噬细胞数量，特别是在注射部位和再生的尾巴处。此外，XtiSCs 注射在尾巴切除后 1 天显著减少了肌肉纤维的降解，并在尾巴切除后 3 天显著促进了新的肌肉生长。此外，全胚胎免疫染色显示一些 XtiSCs 与巨噬细胞共定位。并且我们观察到在用 MitoTracker 染色的蝌蚪尾巴中，XtiSCs 向巨噬细胞的潜在线粒体运输。
我们的研究描绘了 XtiSCs 在促进蝌蚪尾巴切除后肌肉再生中的新作用，强调了与巨噬细胞的独特相互作用，这对再生成功至关重要。这项研究不仅突出了支持细胞在再生医学中的治疗潜力，还为临床转化开辟了道路，为增强组织再生和移植接受的免疫调节策略提供了见解。
