Abstract
The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple growth factors within precise timeframes. In our study, we demonstrated that human adult renal progenitor cells (ARPCs) isolated from urine of both healthy subjects or patients, have the capacity to form spheroids that naturally can form very long tubule-like structures. Importantly, the generation of these tubule-like formations is driven solely by ARPCs, without the need for the external use of chemokines or growth factors to artificially induce the process. These tubule-like structures exhibit expression of structural and functional renal tubule markers and bear, in some cases, striking structural similarities to various nephron regions, including the distal convoluted tubule, the loop of Henle, and proximal convoluted tubules. Furthermore, ARPC spheroids express markers typical of pluripotent cells, such as stage-specific embryonic antigen 4 (SSEA4), secrete elevated levels of renin, and showed angiogenic properties. Notably, ARPCs isolated from urine of patients with IgA nephropathy form spheroids capable of recapitulating the characteristic IgA1 deposition observed in this disease. These findings represent a significant advancement in the field, opening up new avenues for regenerative medicine in the study of kidney development, mechanisms underlying renal disorders, and the development of regenerative therapies for kidney-related ailments.