Creating Renal Spheroids From Adult Human Renal Progenitor Cells in IgA Nephropathy

While the simulation of nephrotoxicity and renal disease and the creation of renal spheroids and organoids from stem cells is a suitable model for drug studies, it requires the use of sophisticated differentiation protocols as well as the administration of growth factors with a precise temporal order.

During a poster session at ASN Kidney Week 2024, researchers from Universita degli Studi di Bari Aldo Moro, Puglia, Italy, led by Fabio Sallustio, PhD, presented data showing that adult human renal progenitor cells (ARPCs) isolated from the urine of healthy subjects or patients with IgA nephropathy (IgAN) can form spheroids and long tubular-like structures naturally, recapitulating typical IgA1 deposits. The poster was titled Renal Progenitor Cells Isolated From Urine of Patients With IgA Nephropathy Formed Renal Spheroids That Can Recapitulate Typical IgA1 Deposition.

An ARPC mixed cell population method was used to generate spheroids and tubular-like structures, characterized by immunofluorescence and flow cytometry, using CD133, NanoG, Oct3/4, GATA-3, SSEA4, CD249, aminopeptidase N, ZO-1, uromodulin, and lotus antibodies. Cell tracking was done using ELISA, CMA assays, and PKH-26.

The spheroids derived from ARPCs with no use of chemokines or growth factors generated very long, tubular-like structures that expressed structural and functional markers of renal tubules sharing structural similarities with regions of nephrons. In addition, high levels of renin were secreted and the spheroids exhibited angiogenic properties.

The researchers generated renal spheroids specific to IgAN patients. After four, eight, and 15 days of culture with patient serum, ARPCs formed spheroids in which IgA1 deposits could be observed (P=.004, P=.0029, and P=.0012, respectively). There was no positive signal detected with inactivated IgAN serum or in spheroids derived from the urine of the healthy patients’ cultures with IgAN serum.

In conclusion, the researchers said, “The ability of urinary ARPCs to form spheroids and differentiate into tubular-like structures without the need for external chemokines is a significant advancement in the field, opening new avenues in the study of pathological mechanisms and for regenerative medicine for kidney diseases.”

Source: Sallustio F, Giannuzzi F, Picerno A, et al. Renal progenitor cells isolated from urine of patients with IgA nephropathy formed renal spheroids that can recapitulate typical IgA1 deposition. TH-PO424. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2024; October 24, 2024; San Diego, California.