Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells.
During early embryogenesis, blood vessels and hematopoietic cells arise from a common precursor cell, the hemangioblast. Recent studies have identified endothelial progenitor cells in the peripheral blood, and there is accumulating evidence that a subset of these cells is derived from precursors in the bone marrow. Here we show that adult bone marrow-derived, phenotypically defined hematopoietic stem cells (c-kit+, Sca-1+, lineage-) give rise to functional endothelial cells. With the exception of the brain, donor-derived cells are rapidly integrated into blood vessels. Durably engrafted endothelial cells express CD31, produce von Willebrand factor, and take up low-density lipoprotein. Analysis of DNA content indicates that donor-derived endothelial cells are not the products of cell fusion. Self-renewal of stem cells with hematopoietic and endothelial cell potential was revealed by serial transplantation studies. The clonal origin of both hematopoietic and endothelial cell outcomes was established by the transfer of a single cell. These results suggest that adult bone marrow-derived hematopoietic stem cells may serve as a reservoir for endothelial cell progenitors.
Bailey
Alexis S
AS
Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
Jiang
Shuguang
S
Afentoulis
Michael
M
Baumann
Christina I
CI
Schroeder
David A
DA
Olson
Susan B
SB
Wong
Melissa H
MH
Fleming
William H
WH
D000818:Animals; D002454:Cell Differentiation; D002999:Clone Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D008077:Lipoproteins, LDL; D008164:Luminescent Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins