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Karger Publishers, Nephron, 10(144), p. 509-524, 2020

DOI: 10.1159/000509425

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Aberrant Differentiation of Human Pluripotent Stem Cell-Derived Kidney Precursor Cells inside Mouse Vascularized Bioreactors

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

<b><i>Background:</i></b> Numerous studies have documented the <i>in vitro</i> differentiation of human pluripotent stem cells (hPSCs) into kidney cells. Fewer studies have followed the fates of such kidney precursor cells (KPCs) inside animals, a more life-like setting. Here, we tested the hypothesis that implanting hPSC-derived KPCs into an <i>in vivo</i> milieu surgically engineered to be highly vascular would enhance their maturation into kidney tissues. <b><i>Methods:</i></b> 3D printed chambers containing KPCs were implanted into the thighs of adult immunodeficient mice. In some chambers, an arterial and venous flow-through (AVFT) was surgically fashioned. After 3 weeks and 3 months, implants were studied by histology, using qualitative and quantitative methods. <b><i>Results:</i></b> After 3 weeks, chambers containing AVFTs were richer in small vessels than contralateral chambers without AVFTs. Glomeruli with capillary loops and diverse types of tubules were detected in all chambers. At 3 months, chambers contained only rudimentary tubules and glomeruli that appeared avascular. In chambers with AVFTs, prominent areas of muscle-like cells were also detected near tubules and the abnormal tissues immunostained for transforming growth factor β1. These features have similarities to renal dysplasia, a typical histological signature of human congenital kidney malformations. <b><i>Conclusions:</i></b> This study urges a note of caution regarding the <i>in vivo</i> fates of hPSC-derived kidney precursors, with pathological differentiation appearing to follow a period of increased vascularity.