Expansion Of Human Umbilical Cord Blood Hematopoietic Progenitors With Cord Vein Pericytes

Abstract

The vascular niche is a site rich in blood vessels, whereas endothelial cells, pericytes, and smooth muscle cells create a microenvironment that recruits mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), which is important for stem cell mobilization, proliferation, and differentiation. In this study, CD146 + pericytes were purified and enriched from the human umbilical cord vein. In order to define their direct role in hematopoiesis, we tested the CD146 + pericytes as compared with osteoblasts derived from umbilical cord blood (UCB) MSCs to sustain human UCB hematopoietic progenitor cells in noncontact coculture settings or in culture media previously conditioned (CM) by these cells. The growth of UCB cells was the greatest in pericyte cocultures (2.8-fold vs. the control). The increased growth in pericyte and pericyte CM cultures was largely the result of increased frequency of CD34 + and CD38 + hematopoietic progenitors, CD34 + CD41 + megakaryocyte progenitors, and CD235 + erythroblasts. A total of 29 factors were found to be secreted by pericytes higher than by osteoblasts. The most secreted growth factor by pericytes was vascular endothelial growth factor (1.3-fold). We demonstrate for the first time that human CD146 + perivascular cell coculture and CM are able to directly support the ex vivo maintenance of human hematopoietic progenitor cells.