Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs

Area of Science:

• Regenerative Medicine
• Biomaterials Engineering
• Vascular Biology

Background:

• Grafted tissue construct perfusion is limited, hindering stem cell therapy success by impacting cell survival and regeneration.
• In vitro pre-vascularized networks offer a promising strategy to enhance blood supply via inosculation with host vasculature.

Purpose of the Study:

• To fabricate in vitro tissue constructs with mature microvascular networks, including perivascular recruitment and basement membrane.
• To leverage dental pulp stem cells' angiogenic properties and endothelial cell self-assembly for capillary formation.

Main Methods:

• Utilized digital scanned light-sheet microscopy to characterize microvascular network generation in collagen hydrogels.
• Quantified perivascular recruitment and performed time-lapse analysis of stem cell recruitment.
• Compared in vitro matured networks with perivascular coverage to those lacking it.

Main Results:

• Demonstrated that platelet-derived growth factor-BB (PDGF-BB) drives perivascular recruitment of dental pulp stem cells.
• Recruited stem cells contributed to vascular basement membrane deposition and vessel maturation.
• In vitro maturation of microvascular networks improved construct blood perfusion and cell survival in vivo.

Conclusions:

• In vitro production of mature microvasculature is crucial for improving cell-based therapies.
• Engineered vascular networks with perivascular support enhance graft integration and function.
• This approach holds strong potential for advancing regenerative medicine applications.