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TISSUE-SPECIFIC STEM CELLS

Isolation and Angiogenesis by Endothelial Progenitors in the Fetal Liver

^a Department of Molecular and Experimental Medicine;
^b Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA

Key Words. Endothelial progenitor cells • Angiogenesis • Murine fetal liver • CD31⁺Sca1⁺ cells

Correspondence: Daniel R. Salomon, M.D., Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Telephone: 858-784-9381; Fax: 858-784-2121; e-mail: dsalomon{at}scripps.edu

Endothelial progenitor cells (EPCs) have significant therapeutic potential. However, the low quantity of such cells available from bone marrow and their limited capacity to proliferate in culture make their use difficult. Here, we present the first definitive demonstration of the presence of true EPCs in murine fetal liver capable of forming blood vessels in vivo connected to the host’s vasculature after transplantation. This population is particularly interesting because it can be obtained at high yield and has a high angiogenic capacity as compared with bone marrow–derived EPCs. The EPC capacity is contained within the CD31⁺Sca1⁺ cell subset. We demonstrate that these cells are dependent for survival and proliferation on a feeder cell monolayer derived from the fetal liver. In addition, we describe a novel and easy method for the isolation and ex vivo proliferation of these EPCs. Finally, we used gene expression profiling and tandem mass spectrometry proteomics to examine the fetal liver endothelial progenitors and the feeder cells to identify possible proangiogenic growth factor and endothelial differentiation-associated genes.

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