41 Ann. N.Y. Acad. Sci. 1044: 41–50 (2005). © 2005 New York Academy of Sciences. doi: 10.1196/annals.1349.006 The Vascular Wall as a Source of Stem Cells MANUELA TAVIAN, a BO ZHENG, b ESTELLE OBERLIN, a MIHAELA CRISAN, c BIN SUN, c JOHNNY HUARD, b AND BRUNO PEAULT a,c a Inserm U506, Hopital Paul Brousse, Villejuif, France b Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA c Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA ABSTRACT: We have characterized the emerging hematopoietic system in the human embryo and fetus. Two embryonic organs, the yolk sac and aorta, sup- port the primary emergence of hematopoietic stem cells (HSCs), but only the latter contributes lymphomyeloid stem cells for definitive, adult-type hemato- poiesis. A common feature of intra- and extraembryonic hematopoiesis is that in both locations hematopoietic cells emerge in close vicinity to vascular endo- thelial cells. We have provided evidence that a population of angiohematopoi- etic mesodermal stem cells, marked by the expression of flk-1 and the novel BB9/ACE antigen, migrate from the paraaortic splanchnopleura into the ven- tral part of the aorta, where they give rise to hemogenic endothelial cells and, in turn, hematopoietic cells. HSCs also appear to develop from endothelium in the embryonic liver and fetal bone marrow, albeit at a much lower frequency. This would imply that the organism does not function during its whole life on a stock of hematopoietic stem cells established in the early embryo, as is usually accepted. We next examined whether the vessel wall can contribute stem cells for other cell lineages, primarily in the model of adult skeletal muscle regener- ation. By immunohistochemistry and flow cytometry, we documented the exist- ence in skeletal muscle, besides genuine endothelial and myogenic cells, of a subset of satellite cells that coexpress endothelial cell markers. This suggested the existence of a continuum of differentiation from vascular cells to endothe- lial cells that was confirmed in long-term culture. The regenerating capacity of these cells expressing both myogenic and endothelial markers is being investi- gated in skeletal and cardiac muscle, and the results are being compared with those generated by satellite cells. Altogether, these results point to a generalized progenitor potential of a subset of endothelial, or endothelium-like, cells in blood vessel walls, in pre- and postnatal life. KEYWORDS: stem cell; embryo; hematopoiesis; endothelium; muscle regeneration Address for correspondence: Dr. Bruno Peault, Department of Pediatrics, University of Pittsburgh and Children’s Hospital of Pittsburgh, 3302 Rangos Research Center, 3460 Fifth Ave., Pittsburgh, PA 15213. Voice: 412-692-6509; fax: 412-692-5837. bruno.peault@chp.edu