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

Area of Science:

• Neuroscience
• Developmental Biology
• Biotechnology

Background:

• Human stem cell-derived models are crucial for studying development and neurodegenerative diseases.
• Cellular immaturity in vitro presents a significant challenge for these models.
• Organ-on-chip systems offer a microenvironment to emulate in vivo conditions and co-culture cell types.

Purpose of the Study:

• To investigate the interaction between human induced pluripotent stem cell-derived spinal motor neurons and brain microvascular endothelial cells (BMECs).
• To determine the influence of microengineered organ-on-chip systems on neuronal maturation.
• To assess the role of vascular-neural interactions in enhancing neuronal function.

Main Methods:

• Derived spinal motor neurons and BMECs from human induced pluripotent stem cells.
• Utilized microengineered organ-on-chip systems for cell co-culture.
• Compared neuronal function and gene expression in organ-on-chip versus traditional 96-well plate cultures.

Main Results:

• Organ-on-chip cultures showed increased calcium transient function and chip-specific gene expression compared to 96-well plates.
• Co-culture with BMECs in the organ-on-chip system promoted vascular-neural interaction and specific gene activation.
• Enhanced neuronal function and in vivo-like signatures were observed in the presence of BMECs within the organ-on-chip.

Conclusions:

• The vascular system exerts specific maturation effects on spinal cord neural tissue.
• Organ-on-chip technology can improve the fidelity of stem cell models, bringing them closer to in vivo conditions.
• This approach facilitates the study of vascular-neural interactions in neuronal development and disease modeling.