Isolating and defining cells to engineer human blood vessels.

Area of Science:

• Regenerative Medicine
• Vascular Biology
• Cell Biology

Background:

• Bone marrow-derived endothelial progenitor cells (EPC) were investigated for their role in neoangiogenesis.
• Recent findings suggest many putative EPCs are hematopoietic cells with proangiogenic, but not vasculogenic, activity.

Purpose of the Study:

• To identify the specific cell population responsible for true vasculogenic activity.
• To explore the potential of these cells for in vivo blood vessel formation and tissue regeneration.

Main Methods:

• Isolation and characterization of circulating endothelial cells with colony-forming cell (ECFC) ability.
• In vivo implantation of ECFCs suspended in extracellular matrix into immunodeficient mice.
• Analysis of blood vessel integration, remodeling, and the impact of matrix properties on vascularization.

Main Results:

• Human ECFCs demonstrated clonal proliferation, endothelial cell markers, and in vivo vasculogenic activity.
• Implanted ECFCs formed integrated human vessels that remodeled into arteries and veins.
• Altering the collagen matrix properties influenced the number and size of newly formed blood vessels.

Conclusions:

• Circulating ECFCs, not bone marrow-derived EPCs, possess true vasculogenic potential.
• The extracellular matrix microenvironment is critical for ECFC-mediated blood vessel formation.
• These findings offer a strategy for vascular bed patterning for tissue and organ regeneration.