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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 16, n. 8 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 16/05311-2 - Regenerative medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes)
Grantee:Mari Cleide Sogayar
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/23345-9 - MicroRNAs, extracellular vesicles and stem cells: physiology, pathophysiological role and therapeutic potential in renal diseases
Grantee:Mirian Aparecida Boim
Support Opportunities: Research Projects - Thematic Grants