Nephron generation in kidney cortices through injection of pretreated mesenchymal stem cell-differentiated tubular epithelial cells

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. •We attempted in vivo nephron generation in kidney cortices for kidney repair using a concept of cellular interactions via conditioned media (CMs).•Vascular endothelial (VECs) and tubular epithelial cells (TECs) did stimulative cross-talks on cell proliferation and tubular changes through their CMs; however, a CM of collecting duct cells (CDCs) suppressed these changes against VECs and TECs.•A CM of CDCs, in addition to a CM of TECs that we reported in a previous study, differentiated mesenchymal stem cells (MSCs) into TECs.•Successful nephron generation in kidney cortices by injecting pretreated MSC-differentiated tubular epithelial cells.•Our method of injecting pretreated TECs into kidney cortices might have applications for repairing dysfunctional kidney tissue.