Collagen matrix physical properties modulate endothelial colony forming cell-derived vessels in vivo

Abstract

Developing tissue engineering approaches to generate functional vascular networks is important for improving treatments of peripheral and cardiovascular disease. Endothelial colony forming cells (ECFCs) are an endothelial progenitor cell (EPC) population defined by high proliferative potential and an ability to vascularize collagen-based matrices in vivo. Little is known regarding how physical properties of the local cell microenvironment guide vessel formation following EPC transplantation. In vitro evidence suggests that collagen matrix stiffness may modulate EPC vessel formation. The present study determined the ability of 3D collagen matrix physical properties, varied by changing collagen concentration, to influence ECFC vasculogenesis in vivo. Human umbilical cord blood ECFCs were cultured within matrices for 18 h in vitro and then fixed for in vitro analysis or implanted subcutaneously into the flank of immunodeficient mice for 14 days. We report that increasing collagen concentration significantly decreased ECFC derived vessels per area (density), but significantly increased vessel sizes (total cross sectional area). These results demonstrate that the physical properties of collagen matrices influence ECFC vasculogenesis in vivo and that by modulating these properties, one can guide vascularization.

Integration and Regression of Implanted Engineered Human Vascular Networks During Deep Wound Healing

“…5Ai). Analyzing the human blood vessels, we found that they increased in size around the wound area during the proliferation period (days 5-7), then they regressed (days [11][12][13][14] and were further stabilized late in remodeling period (day 21), whereas the majority of microvessels (i.e., with a vessel area less than 200 m 2 ) remained (Fig. 5Aii).…”

“…Through the transitions from inflammation to proliferation (days 5-7), approximately 28.21 Ϯ 4.57% of human vessels were covered by mouse SMCs. This percentage increased through the transitions from inflammation to proliferation (days [11][12][13][14], reaching 79.35 Ϯ 6. 51% at the late remodeling stage (day 21; Fig.…”

“…To test this, we followed the integration kinetics of the human vasculature during the progression in wound healing from the inflammation stage (day 3), through the transitions from inflammation to proliferation (days 5-7) and from proliferation to remodeling (days [11][12][13][14], and to the late remodeling stage (day 21; Fig. 2A).…”

“…4Ai). Some of these large vessels were positive for Wound analysis during inflammation to proliferation periods (days [11][12][13][14]. After the treatment with human microvascular constructs, the wounds were analyzed at day 11 (A) and day 14 (B).…”

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

“…72 Insufficient vascular network formation and maintenance drives many of these clinical disorders including diabetes, arthritis, atherosclerosis, and peripheral artery disease. 20,35 Local tissue ischemia resultant of insufficient blood flow is a potent stimulus for recruitment of progenitor blood forming cells including endothelial progenitor cells (EPCs). 63 EPCs are pivotal to maintaining vascular homeostasis and repair from injury.…”