Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

Ashwani Kumar Gupta; Prasenjit Sarkar; Jason A. Wertheim; Xinchao Pan; Thomas J. Carroll; Leif Oxburgh

doi:10.1038/s42003-020-0948-7

Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

Ashwani Kumar Gupta, Prasenjit Sarkar, Jason A. Wertheim, Xinchao Pan, Thomas J. Carroll, Leif Oxburgh^*

^*Corresponding author for this work

Surgery, Transplant Surgery Division

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

A fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and heterochronic organoids were well vascularized when engrafted under the kidney capsule. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed, but despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study. We propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop similar stromal overgrowth when engrafted under the kidney capsule.

Original language	English (US)
Article number	231
Journal	Communications Biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-0948-7
State	Published - Dec 1 2020

Funding

We would like to express our gratitude to Dr. Andrew McMahon and Tracy Tran at University of Southern California for sharing the H9-FP cells. The project described was supported by the National Institutes of Health grant number R24 DK106743 to L.O. and T.C. and Department of Veterans Affairs grant 01BX002660 to J.A.W. Core facilities support was provided by Maine Medical Center Research Institute core facilities for Molecular Phenotyping, Progenitor Cell Analysis, Microscopy, and Small Animal Imaging. A special thanks to Terry Henderson at the Maine Medical Center Research Institute Small Animal Imaging core for help with Micro-CT measurements. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Department of Veterans Affairs.

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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abstract = "A fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and heterochronic organoids were well vascularized when engrafted under the kidney capsule. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed, but despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study. We propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop similar stromal overgrowth when engrafted under the kidney capsule.",

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AU - Oxburgh, Leif

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Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

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