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Abstract: TH-PO424

Renal Progenitor Cells Isolated from Urine of Patients with IgA Nephropathy Formed Renal Spheroids That Can Recapitulate Typical IgA1 Deposition

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Sallustio, Fabio, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Giannuzzi, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Picerno, Angela, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Maiullari, Silvia, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Montenegro, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Cicirelli, Antonella, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Stasi, Alessandra, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • De Palma, Giuseppe, Istituto Tumori Bari Giovanni Paolo II IRCCS, Bari, Puglia, Italy
  • Pertosa, Giovanni B., Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Pontrelli, Paola, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Rossini, Michele, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Puglia, Italy
  • Di leo, Vincenzo, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Errede, Mariella, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Tamma, Roberto, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Ribatti, Domenico, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
Background

The creation of renal spheroids and organoids from stem cells represents a suitable model for drug studies and in the simulation of nephrotoxicity and renal disease. However, it requires the use of sophisticated differentiation protocols and the administration of growth factors with a precise temporal order. Here we show 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.

Methods

Spheroids and tubular-like structures were generated by using an ARPC mixed cell population method and characterized by immunofluorescence and flow cytometry, using CD133, NanoG, Oct3/4, GATA-3, SSEA4, CD249, Aminopeptidase N, ZO-1, Uromodulin, and Lotus antibodies.ELISA;CAM assays; PKH-26 labeling was used for cell tracking.

Results

Spheroids derived from ARPCs without the 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, such as the distal convoluted tubule, loop of Henle and the proximal convoluted tubules. Furthermore, the spheroids secreted high levels of renin and exhibited angiogenic properties. To study whether spheroids derived by urinary ARPCs can be used to establish in vitro models recapitulating renal diseases, we generated IgAN patient-specific renal spheroids. ARPCs formed spheroids in which IgA1 deposits could be observed after 4, 8 and 15 days of culture with patient serum (p=0.004, p=0.0029 and p=0.0012, respectively). In contrast, no positive signal was detected either with inactivated IgAN serum or in spheroids derived from the urine of healthy patients cultured with IgAN serum.

Conclusion

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 in the for regenerative medicine for kidney diseases.

Funding

  • Government Support – Non-U.S.