Kidney organoids generated from erythroid progenitors cells of patients with autosomal dominant polycystic kidney disease

Autor(es)

Facioli, Roberta ^[1] ; Lojudice, Fernando Henrique ^[2] ; Anauate, Ana Carolina ^[1] ; Maquigussa, Edgar ^[1] ; Nishiura, Jose Luiz ^[1] ; Heilberg, Ita Pfeferman ^[1] ; Sogayar, Mari Cleide ^{[3, 2]} ; Boim, Mirian Aparecida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Cell & Mol Therapy Ctr NUCEL, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 16, n. 8 2021.
• Citações Web of Science: 0

Resumo

Background Kidney organoids have been broadly obtained from commercially available induced pluripotent stem cells (iPSCs); however, it has been a great challenge to efficiently produce renal organoid models from patients with autosomal dominant polycystic kidney disease (ADPKD) that recapitulate both embryogenesis and the mechanisms of cystogenesis. Methods Blood erythroid progenitors (EPs) from two ADPKD patients and one healthy donor (HC) was used as a comparative control to normalize the many technical steps for reprogramming EPs and for the organoids generation. EPs were reprogrammed by an episomal vector into iPSCs, which were differentiated into renal tubular organoids and then stimulated by forskolin to induce cysts formation. Results iPSCs derived from EPs exhibited all characteristics of pluripotency and were able to differentiate into all three germ layers. 3D tubular organoids were generated from single cells after 28 days in Matrigel. HC and ADPKD organoids did not spontaneously form cysts, but upon forskolin stimulation, cysts-like structures were observed in the ADPKD organoids but not in the HC-derived organoids. Conclusion The findings of this study showed that kidney organoids were successfully generated from the blood EP cells of ADPKD patients and a healthy control donor. This approach should contribute as a powerful tool for embryonic kidney development model, which is able to recapitulate the very early pathophysiological mechanisms involved in cytogenesis. (AU)

• Processo FAPESP: 16/05311-2 - Medicina regenerativa visando à terapia de doenças crônico-degenerativas (câncer e diabetes)
• Beneficiário: Mari Cleide Sogayar
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/23345-9 - MicroRNAs, vesículas extracelulares e células tronco: papel fisiológico, fisiopatológico e potencialidade terapêutica em doenças renais
• Beneficiário: Mirian Aparecida Boim
• Modalidade de apoio: Auxílio à Pesquisa - Temático