A Vascularized Human Organ Chip Reveals SARS-CoV-2 Susceptibility in Developmentally Guided Tissue Maturation

Stem cell-derived models offer traceable cell sources for studying tissue development and disease mechanisms. However, many such models have inherently immature or fetal-like phenotypes, limiting their relevance for mechanistic studies of specialized adult tissues. Clinical observations suggest a potential link between epithelial cells and their transit-amplifying progenitors in disease onset and viral tropism, but experimental validation is needed. This study aimed to develop mature visceral epithelial cells (podocytes) from human induced pluripotent stem (iPS) cells using a developmental approach and model severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a vascularized microfluidic kidney-on-a-chip platform exhibiting in vivo-like tissue structure and function.