# Transplantation of Endothelial Progenitor Cells Solely Leads to Development of Functional Neo-vessels in vivo

## TL;DR

This study shows that endothelial colony-forming cells alone can create functional blood vessels in mice, potentially simplifying regenerative medicine.

## Contribution

Demonstrates that single-cell transplants of ECFCs can form stable vessels without co-transplanting other cell types.

## Key findings

- Single ECFC transplants with higher cell numbers form stable vessels as effectively as co-transplants with MSPC.
- White adipose tissue-derived ECFCs are most effective at forming micro-vessels in vivo.
- Higher cell dosage of ECFCs is essential for successful vasculogenesis.

## Abstract

It has been believed that de novo vessel formation (neo-vasculogenesis) can be induced by co-transplantation of pericytes or mesenchymal stem/progenitor cells (MSPC) with endothelial cells or endothelial colony-forming cells (ECFC). The requirement for co-transplantation of two adult progenitor cells is one factor that can potentially complicate the process of therapeutic vasculogenesis which hampers the development of strategies for therapeutic intervention referred to as ‘regenerative medicine’. Here we employed a novel strategy for therapeutic vessel development by transplanting endothelial colony forming progenitor cells solely to immune compromised mice and detect vessel formation capacity of single ECFC transplants compared to ECFC/MSPC co-transplants. We applied umbilical cord derived and bone marrow derived-MSPC and umbilical cord derived ECFC with different total cell number for subcutaneous transplantation in matrix composites either alone or mixed at a ratio of 1:5 subcutaneously into immune deficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ; NSG mice. Implants were harvested one day, one, two, eight and 24 weeks after transplantation for detecting the state of vessel formation and stability of the transplants by histological assessments. Additionally, endothelial progenitor cells derived from various human tissues such as umbilical cord blood, peripheral blood and white adipose tissue were used to assess their potential for vessel formation in vivo.

Results confirmed that single transplantation of ECFCs with a higher cell number and later in the time course after transplantation is as efficient as co-transplantation of ECFC with MSPC at forming stable-perfused human vessels. Amongst ECFCs isolated from different human sources, white adipose tissue derived ECFC are most potent in forming neo-vessels (micro-vessels) in vivo, thus WAT-ECFC could be an optimal cell for vasculogenesis regenerative application.

Co-transplantation of ECFC and MSPC with the defined 5:1 ratio or sole ECFC with a higher cell dosage was essential for vessel generation in vivo.