Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor Cells

TLDR

Therapeutic vascularization and tissue engineering require human cells that are readily available, expandable ex vivo, and capable of forming robust vasculature in vivo. The study aims to create functional microvascular beds in immunodeficient mice by co‑implanting human endothelial and mesenchymal progenitor cells isolated from blood and bone marrow. The authors achieved this by implanting the progenitor cells together into the mice, allowing them to form interconnected microvascular networks. One week after implantation, the constructs formed extensive human blood vessel networks with erythrocytes and functional anastomoses; endothelial progenitors lined the lumens while mesenchymal progenitors surrounded them, and the networks remained patent at four weeks, demonstrating rapid, durable microvascular formation from noninvasive progenitors.

Abstract

The success of therapeutic vascularization and tissue engineering will rely on our ability to create vascular networks using human cells that can be obtained readily, can be expanded safely ex vivo, and can produce robust vasculogenic activity in vivo. Here we describe the formation of functional microvascular beds in immunodeficient mice by coimplantation of human endothelial and mesenchymal progenitor cells isolated from blood and bone marrow. Evaluation of implants after 1 week revealed an extensive network of human blood vessels containing erythrocytes, indicating the rapid formation of functional anastomoses within the host vasculature. The implanted endothelial progenitor cells were restricted to the luminal aspect of the vessels; mesenchymal progenitor cells were adjacent to lumens, confirming their role as perivascular cells. Importantly, the engineered vascular networks remained patent at 4 weeks in vivo. This rapid formation of long-lasting microvascular networks by postnatal progenitor cells obtained from noninvasive sources constitutes an important step forward in the development of clinical strategies for tissue vascularization.