Characterizing On-Chip Angiogenesis Induction in a Microphysiological System as a Functional Measure of Mesenchymal...

Area of Science:

• Cell Biology
• Regenerative Medicine
• Biotechnology

Background:

• Mesenchymal stromal cells (MSCs) are investigated for regenerative therapies due to their potential to stimulate angiogenesis.
• Functional heterogeneity and manufacturing challenges hinder MSC clinical success and quality control.
• Standardized potency assays are needed to ensure consistent MSC product quality.

Purpose of the Study:

• To develop and validate a quantitative bioassay using a microphysiological system (MPS) to measure MSC angiogenic potency.
• To assess the heterogeneity of MSCs from different donors and passages in stimulating angiogenesis.
• To explore MSC angiogenic bioactivity as a potential potency attribute for quality control.

Main Methods:

• Development of an enhanced-throughput microphysiological system (MPS) for co-culturing MSCs and human umbilical vein endothelial cells.
• Quantitative assessment of MSC-induced angiogenesis, including tip and stalk cell phenotypes.
• Correlation of angiogenic potency with MSC donor source, passage number, and hepatocyte growth factor (HGF) expression.

Main Results:

• Significant heterogeneity in MSC angiogenic potency was observed across different donors and cell passages.
• MSC potency varied in promoting tip cell-dominant versus stalk cell-dominant angiogenic phenotypes.
• Angiogenic bioactivity correlated with hepatocyte growth factor (HGF) expression levels.

Conclusions:

• MSC angiogenic bioactivity is a potential potency attribute for MSC quality control strategies.
• The developed MPS bioassay effectively quantifies MSC angiogenic potency and reveals donor- and passage-dependent heterogeneity.
• Reliable potency assays are essential for improving MSC product consistency and accelerating clinical development.