Flow-enhanced vascularization and maturation of kidney organoids in vitro

By Kimberly A. Homan, Navin R Gupta, Katharina T. Kroll, David Kolesky, Mark A. Skylar-Scott, Tomoya Miyoshi, Donald Mau, M. T. Valerius, Thomas C. Ferrante, Joseph V. Bonventre and 2 more. Nature Methods, 2019

796 citations recorded by the source corpus.

Kidney organoids derived from human pluripotent stem cells have glomerular- and tubular-like compartments that are largely avascular and immature in static culture. Here we report an in vitro method for culturing kidney organoids under flow on millifluidic chips, which expands their endogenous pool of endothelial progenitor cells and generates vascular networks with perfusable lumens surrounded by mural cells. We found that vascularized kidney organoids cultured under flow had more mature podocyte and tubular compartments with enhanced cellular polarity and adult gene expression compared with that in static controls. Glomerular vascular development progressed through intermediate stages akin to those involved in the embryonic mammalian kidney’s formation of capillary loops abutting foot processes. The association of vessels with these compartments was reduced after disruption of the endogenous VEGF gradient. The ability to induce substantial vascularization and morphological maturation of kidney organoids in vitro under flow opens new avenues for studies of kidney development, disease, and regeneration. Culturing human kidney organoids under fluidic shear conditions leads to robust vascularization and increased maturity. These kidney organoids should serve as a better model for kidney development than those developed in static culture.

Subfields: Molecular Biology, Public Health, Environmental and Occupational Health, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/99a496a475cfddb99b38dd0a88ff85bf21c62e51

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1. Mark A. Skylar-Scott
2. J. Lewis
3. Ryan L. Truby
4. S. Uzel
5. Lucy Nam
6. John H Ahrens
7. Sarita Damaraju
8. A. Bastola

Citations in the corpus

• Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels (2019, methodology): “In addition, we envision adopting new protocols, such as those recently reported for renal organoids (19), that offer a pathway to creating more mature, microvascularized OBBs.”