Aberrant differentiation of human pluripotent stem cell-derived kidney precursor cells inside mouse vascularized bioreactors

Background. Numerous studies have documented the in vitro 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 in vivo milieu surgically engineered to be high vascular would enhance their maturation into kidney tissues.

Methods. 3D printed chambers containing KPCs were implanted into thighs of adult immunodeficient mice. In some chambers, an arterial and venous flow-through (AVFT) was surgically fashioned. After three weeks and three months, implants were studied by histology, using qualitative and quantitative methods.

Results. After three 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 three 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 b1. These features have similarities to renal dysplasia, a typical histological signature of human congenital kidney malformations.

Conclusions. This study urges a note of caution regarding the in vivo fates of hPSC-derived kidney precursors, with pathological differentiation appearing to follow a period of increased vascularity.