Enhanced Neovascularization by Simultaneous Transplantation of Peripheral Blood CD34+ Hematopoietic Stem Cells and CD14+ Monocytes

Abstract

Formation of new blood vessels is required for normal embryonic development and healing of damaged tissues, but also is essential for tumor growth. Although CD34+VEGF-R2(KDR)+ endothelial progenitor cells and CD14+ monocytes in human peripheral blood are known to actively participate in angiogenesis and vasculogenesis, the clear role of monocytes in the process of neovascularization is matter of debate. Here, we investigated whether a combination of two types of cells shows synergism in tumor-induced neovascularization. Fluorescently labeled purified CD34+ HSCs, CD14+ monocytes or combination of CD34+ HSCs and CD14+ monocytes were intratumorally injected into nude mice bearing human tumor of pancreatic adenocarcinoma. CD14+ monocytes or combination of CD34+ HSCs and CD14+ monocytes. Injection of a mixture of the 2 subsets resulted in improved neovascularization in vivo to any single-cell-type transplantation. These data demonstrate that human CD14+ monocytes as well as CD34+ HSCs can differentiate along the endothelial lineage in a specific permissive environment and thus this combination represent an autologous transplantable cell source for therapeutic neovasculogenesis