Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

Published in: Stem Cell Reports

Human stemcell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brainmicrovascular endothelial cells (BMECs) share commonsignaling pathwayswithneurons early indevelopment, but their contribution to human neuronalmaturation is largely unknown. To study this interaction and influence ofmicroculture, we derived both spinal motor neurons and BMECs fromhumaninduced pluripotent stemcells and observed increased calciumtransient functionandChip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular systems specificmaturation effects on spinal cord neural tissue, and the use of Organ-Chips canmove stemcellmodels closer to an in vivo condition.