Endothelial/Mesenchymal Stem Cell Crosstalk Within Bioprinted Cocultures

Area of Science:

• Biomaterials and Tissue Engineering
• Cell Biology and Angiogenesis
• Regenerative Medicine

Background:

• Vascularization is essential for viable tissue surrogates in tissue engineering.
• Coculturing endothelial cells (ECs) and mesenchymal stem cells (MSCs) is a promising approach for scaffold vascularization.
• Conflicting reports exist regarding the proangiogenic or antiangiogenic role of MSCs and their contribution to pathway regulation.

Purpose of the Study:

• To investigate the regulation of angiogenic and arteriogenic pathways in EC:MSC cocultures within bioprinted scaffolds.
• To elucidate the distinct roles of ECs and MSCs in modulating these pathways.
• To clarify the dose- and time-dependent effects of MSCs on ECs.

Main Methods:

• Fabrication of scaffolds with varying EC:MSC ratios using extrusion-based bioprinting.
• Coculture of human ECs with rat or human MSCs in hybrid systems.
• Analysis of DNA, gene, and protein expression to assess angiogenic and arteriogenic pathway regulation.

Main Results:

• MSCs exert a dose-dependent inhibitory effect on EC angiogenic factor expression within 24 hours.
• MSCs demonstrate a proangiogenic effect within one week of coculture.
• Juxtacrine signaling (co-encapsulation) promotes vascular endothelial growth factor secretion, while paracrine signaling (adjacent scaffolds) promotes platelet-derived growth factor secretion.

Conclusions:

• Bioprinted EC:MSC interplay systems effectively elucidate cell-cell interactions for vascular tissue engineering.
• MSCs exhibit a biphasic effect on angiogenesis, initially inhibitory then proangiogenic, mimicking in vivo dynamics.
• MSC presence is critical for regulating arteriogenesis pathways, resolving conflicting literature findings and informing scaffold design.