Ex Vivo Expanded 3D Human Kidney Spheres Engraft Long Term and Repair Chronic Renal Injury in Mice

Orit Harari-Steinberg, Dorit Omer, Yehudit Gnatek, Oren Pleniceanu, Sanja Goldberg, Osnat Cohen-Zontag, Sara Pri-Chen, Itamar Kanter, Nissim Ben Haim, Eli Becker, Roi Ankawa, Yaron Fuchs, Tomer Kalisky, Zohar Dotan, Benjamin Dekel

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Human kidney cells quickly degenerate in culture, precluding them as a source for cell therapy for chronic kidney disease (CKD). Herein, Harari-Steinberg et al. show that upon culturing as 3D nephrospheres, human kidney cells regain their epithelial phenotype and acquire in vivo tissue-forming and reparative properties in a CKD mouse model.

Original languageEnglish
Pages (from-to)852-869.e4
JournalCell Reports
Volume30
Issue number3
DOIs
StatePublished - 21 Jan 2020

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Funding

We wish to thank the entire staff at the Pediatric Stem Cell Research Institute at the Sheba Medical Center for the fruitful discussions. We wish to thank Dr. Tali Bar-Lev from the Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA) at Bar-Ilan University for assistance with the bioinformatic experiments, Michael Namestnikov for assistance with generating the summarizing scheme, and the Israel National Center for Personalized Medicine (INCMP) for their assistance in sequencing and analysis. This study was supported by KidneyCure Bio and the Sheba Medical Center (B.D.) and the Israel Science Foundation (ICORE 1902/12 and grants 1634/13 and 2017/13), the Israel Ministry of Health (grant 3-10146), and the European Union (EU) Seventh Framework Programme (FP7) (Marie Curie International Reintegration grant 618592) (T.K.). Experiment Design, O.H.-S. D.O. and B.D.; Experiment Performance, D.O. Y.G. S.G. O.C.-Z. S.P.-C. Y.F. and Z.D.; Data Analysis and Manuscript Writing, O.H.-S. D.O. O.P. and B.D.; RNA Quality Checks for Sequencing, I.K. and T.K.; RNA-Seq Data Preprocessing and Analysis, O.H.S, O.C.-Z. I.K. N.B.H. E.B. and T.K. B.D is a co-founder, shareholder, and board member at KidneyCure. O.H.S is a shareholder at KidneyCure. We wish to thank the entire staff at the Pediatric Stem Cell Research Institute at the Sheba Medical Center for the fruitful discussions. We wish to thank Dr. Tali Bar-Lev from the Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA) at Bar-Ilan University for assistance with the bioinformatic experiments, Michael Namestnikov for assistance with generating the summarizing scheme, and the Israel National Center for Personalized Medicine (INCMP) for their assistance in sequencing and analysis. This study was supported by KidneyCure Bio and the Sheba Medical Center (B.D.) and the Israel Science Foundation (ICORE 1902/12 and grants 1634/13 and 2017/13 ), the Israel Ministry of Health (grant 3-10146 ), and the European Union ( EU ) Seventh Framework Programme ( FP7 ) (Marie Curie International Reintegration grant 618592 ) (T.K.).

FundersFunder number
BINA
Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials
INCMP
Israel Ministry of Health
Israel National Center for Personalized Medicine
KidneyCure Bio
Marie Curie International Reintegration
Pediatric Stem Cell Research Institute at the Sheba Medical Center
Sheba Medical Center
Union ( EU ) Seventh Framework Programme
European Commission
Israel Science Foundation2017/13, ICORE 1902/12, 1634/13
Seventh Framework Programme618592
Ministry of Health, State of Israel3-10146

    Keywords

    • 3D culture
    • 5/6 nephrectomy
    • antifibrotic effect
    • autologous treatment
    • in vivo differentiation
    • kidney regeneration
    • kidney stem cells
    • mouse CKD model
    • nephrospheres
    • renal epithelial differentiation

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