Original Paper

Angiogenesis

, Volume 16, Issue 4, pp 735-744

First online:

Human white adipose tissue vasculature contains endothelial colony-forming cells with robust in vivo vasculogenic potential

  • Ruei-Zeng LinAffiliated withDepartment of Cardiac Surgery, Boston Children’s Hospital, Harvard Medical School
  • , Rafael Moreno-LunaAffiliated withDepartment of Cardiac Surgery, Boston Children’s Hospital, Harvard Medical SchoolInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular (UCAMI-UCERV)
  • , Rocio Muñoz-HernandezAffiliated withInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Unidad Clínico-Experimental de Riesgo Vascular (UCAMI-UCERV)
  • , Dan LiAffiliated withCenter for Vascular Biology, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School
  • , Shou-Ching S. JaminetAffiliated withCenter for Vascular Biology, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School
  • , Arin K. GreeneAffiliated withDepartment of Plastic and Oral Surgery, Boston Children’s Hospital, Harvard Medical School
  • , Juan M. Melero-MartinAffiliated withDepartment of Cardiac Surgery, Boston Children’s Hospital, Harvard Medical School Email author 

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Abstract

Blood-derived endothelial colony-forming cells (ECFCs) have robust vasculogenic potential that can be exploited to bioengineer long-lasting human vascular networks in vivo. However, circulating ECFCs are exceedingly rare in adult peripheral blood. Because the mechanism by which ECFCs are mobilized into circulation is currently unknown, the reliability of peripheral blood as a clinical source of ECFCs remains a concern. Thus, there is a need to find alternative sources of autologous ECFCs. Here we aimed to determine whether ECFCs reside in the vasculature of human white adipose tissue (WAT) and to evaluate if WAT-derived ECFCs have equal clinical potential to blood-derived ECFCs. We isolated the complete endothelial cell (EC) population from intact biopsies of normal human subcutaneous WAT by enzymatic digestion and selection of CD31+ cells. Subsequently, we extensively compared WAT-derived EC phenotype and functionality to bonafide ECFCs derived from both umbilical cord blood and adult peripheral blood. We demonstrated that human WAT is indeed a dependable source of ECFCs with indistinguishable properties to adult peripheral blood ECFCs, including hierarchical clonogenic ability, large expansion potential, stable endothelial phenotype, and robust in vivo blood vessel-forming capacity. Considering the unreliability and low rate of occurrence of ECFCs in adult blood and that biopsies of WAT can be obtained with minimal intervention in an ambulatory setting, our results indicate WAT as a more practical alternative to obtain large amounts of readily available autologous ECFCs for future vascular cell therapies.

Keywords

Endothelial colony-forming cells Endothelial progenitor cells Adipose tissue Peripheral blood Vasculogenesis