Laboratory of Organ and Tissue Reconstruction, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Laboratory of Organ and Tissue Reconstruction, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Biochem Biophys Res Commun. 2019 Oct 8;518(1):141-147. doi: 10.1016/j.bbrc.2019.08.022. Epub 2019 Aug 13.
Transplantation of artificially treated metanephroi or pluripotent stem cell-injected blastocyst-derived whole kidneys will be established in the near future as a useful therapeutic method for renal failure. We have attempted in vivo nephron generation for kidney repair by exploiting cellular interactions via conditioned media (CMs). In a previous report, we showed stimulative cross-talks between vascular endothelial cells (VECs) and tubular epithelial cells (TECs) on cell proliferation and morphological changes, the differentiation of mesenchymal stem cells (MSCs) into TECs by TEC-CM, and nephron generation from TECs or MSCs in rat subcutaneous spaces. In this study adding collecting duct cells (CDCs) and their CM, we demonstrate the suppressive actions of CDC-CM against VECs and TECs, in addition to stimulative cross-talks between VECs and TECs, during the above changes. Furthermore, CDC-CM, similar to TEC-CM, caused differentiation of MSCs into TECs. Thus, we injected CDC-CM-induced MSC-differentiated TECs into rat kidney cortices. The pretreatment of cells in 3-dimensional culture using a small amount of gel complex before implantation triggered the generation of much more nephron-like structures, compared to the implantation of non-pretreated cells. Our method of injecting pretreated TECs into kidney cortices might have applications for repairing dysfunctional kidney tissue.
在不久的将来，通过使用条件培养基 (CM) 利用细胞间的相互作用，将经过人工处理的肾原基或注入多能干细胞的胚泡衍生的全肾移植将成为治疗肾衰竭的有效方法。我们曾试图通过条件培养基（CM）利用细胞间的相互作用来实现体内肾单位生成，以修复肾脏。在之前的报告中，我们展示了血管内皮细胞 (VEC) 和肾小管上皮细胞 (TEC) 之间的刺激对话，促进了间充质干细胞 (MSC) 向 TEC 的分化，以及 TEC 或 MSC 在大鼠皮下空间中肾单位的生成。在这项研究中添加了集合管细胞 (CDC) 和它们的 CM，我们证明了除了 VEC 和 TEC 之间的刺激对话外，CDC-CM 对 VEC 和 TEC 也具有抑制作用。此外，CDC-CM 类似于 TEC-CM，可诱导 MSC 分化为 TEC。因此，我们将经 CDC-CM 诱导分化的 MSC-TEC 注入大鼠肾脏皮质。与未预处理细胞的植入相比，在植入前使用少量凝胶复合物对 3 维培养的细胞进行预处理可触发更多类肾单位结构的生成。我们将预处理的 TEC 注射到肾脏皮质中的方法可能适用于修复功能失调的肾脏组织。
