Mesangial cell regeneration from exogenous stromal progenitor by utilizing embryonic kidney

Abstract

Kidney regenerative medicine is expected to be the solution to the shortage of organs for transplantation. In a previous report, we transplanted exogenous renal progenitor cells (RPCs) including nephron progenitor cells (NPCs), stromal progenitor cells (SPCs), and the ureteric bud (UB) into the nephrogenic zone of animal embryos and succeeded in regenerating new nephrons from exogenous NPCs through a fetal developmental program. However, it was unknown whether the renal stromal lineage cells were regenerated from SPCs. The present study aimed to verify the differentiation of SPCs into mesangial cells and renal stromal lineage cells. Here, we found that simply transplanting RPCs, including SPCs, into the nephrogenic zone of wild-type fetal mice was insufficient for differentiation of SPCs. Therefore, to enrich the purity of SPCs, we sorted cells from RPCs by targeting platelet-derived growth factor receptor alpha (PDGFRa) which is a cell surface marker for immature stromal cells and transplanted the PDGFRa-positive sorted cells. As a result, we succeeded in regenerating a large number of mesangial cells and other renal stromal lineage cells including interstitial fibroblasts, vascular pericytes, and juxtaglomerular cells. We have established the method for regeneration of stromal cells from exogenous SPCs that may contribute to various fields, such as regenerative medicine and kidney embryology, and the creation of disease models for renal stromal disorders.