Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

Document Type

Article

Publication Date

5-11-2020

Institution/Department

MaineHealth Institute for Research

Journal Title

Communications biology

MeSH Headings

Animals; Cell Differentiation; Cell Line; Female; Humans; Kidney (growth & development); Male; Mice; Organogenesis (physiology); Organoids (growth & development); Pluripotent Stem Cells (transplantation)

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.

First Page

231

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