The Vascular Wall as a Source of Stem Cells

Inserm U506, Hopital Paul Brousse, Villejuif, France.
Annals of the New York Academy of Sciences (Impact Factor: 4.31). 07/2005; 1044(1):41-50. DOI: 10.1196/annals.1349.006
Source: PubMed

ABSTRACT We have characterized the emerging hematopoietic system in the human embryo and fetus. Two embryonic organs, the yolk sac and aorta, support the primary emergence of hematopoietic stem cells (HSCs), but only the latter contributes lymphomyeloid stem cells for definitive, adult-type hematopoiesis. A common feature of intra- and extraembryonic hematopoiesis is that in both locations hematopoietic cells emerge in close vicinity to vascular endothelial cells. We have provided evidence that a population of angiohematopoietic mesodermal stem cells, marked by the expression of flk-1 and the novel BB9/ACE antigen, migrate from the paraaortic splanchnopleura into the ventral 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 regeneration. By immunohistochemistry and flow cytometry, we documented the existence 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 endothelial cells that was confirmed in long-term culture. The regenerating capacity of these cells expressing both myogenic and endothelial markers is being investigated 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.

Download full-text


Available from: Estelle Oberlin, Jul 07, 2015
  • Source
    • "Komórki o różnym potencjale i na różnym etapie różnicowania , opisane w biostrukturze naczyń, przedstawiane są jako rezydentne/spoczynkowe macierzyste i progenitorowe komórki ścian naczyń krwionośnych VW-SC/ PC [1] [14] [24] [29] [39] [41] [48] [54] [79] [81] [83] [86] [88]. Identyfikacja komórek progenitorowych dla śródbłonków naczyniowych we krwi obwodowej C-EPC [3], szpiku kostnym BM-EPC, krwi pępowinowej UC-EPC, a także odkrycie klastrów komórek macierzystych i progenitorowych w obrębie zróżnicowanych tkanek i narządów [29] [73] [79] stanowi wystarczający dowód, że mechanizmy, których aktywność pozwala na rozwój organizmu w okresie życia prenatalnego są również obecne i aktywne w życiu postnatalnym [88]. Komórki VW-SC/PC spoczywające w środowisku nisz komórkowych zróżnicowanych "
    [Show abstract] [Hide abstract]
    ABSTRACT: Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2013; 67:982-995. DOI:10.5604/17322693.1067258 · 0.63 Impact Factor
  • Source
    • "The hematopoietic cells emerge in close vicinity to vascular endothelial cells in both intra and extraembryonic hematopoiesis. Specifically, a population of angiohematopoietic stem cells expressing flk-1 and angiotensin-converting enzyme (ACE) migrates from the para-aortic splanchnopleura into the ventral part of the aorta, where they give rise to hemogenic endothelial cells and subsequently hematopoietic cells [25]. Furthermore, hematopoietic cells also appear to develop from endothelium in the embryonic liver and fetal bone marrow, albeit at a much lower frequency. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Multipotent stem/progenitor cells with similar developmental potentials have been independently identified from diverse human tissue/organ cultures. The increasing recognition of the vascular/perivascular origin of mesenchymal precursors suggested blood vessels being a systemic source of adult stem/progenitor cells. Our group and other laboratories recently isolated multiple stem/progenitor cell subsets from blood vessels of adult human tissues. Each of the three structural layers of blood vessels: intima, media, and adventitia has been found to include at least one precursor population, that is, myogenic endothelial cells (MECs), pericytes, and adventitial cells (ACs), respectively. MECs and pericytes efficiently regenerate myofibers in injured and dystrophic skeletal muscles as well as improve cardiac function after myocardial infarction. The applications of ACs in vascular remodeling and angiogenesis/vasculogenesis have been examined. Our recent finding that MECs and pericytes can be purified from cryogenically banked human primary muscle cell culture further indicates their potential applications in personalized regenerative medicine.
    BioMed Research International 02/2012; 2012:597439. DOI:10.1155/2012/597439 · 2.71 Impact Factor
  • Source
    • "These 'hemogenic' aortic endothelial cells appear to undergo a phenotypic switch and establish specialized intra-aortic HSC-bearing 'clusters' that are in continuity with the luminal surface of the dorsal aortic floor, and which are marked by Runx1 expression (Jaffredo et al. 1998; North et al. 2002; Dieterlen-Lievre et al. 2006). Human data, although limited, also suggest that intra-embryonic HSCs may arise from aortic endothelial cells (Tavian et al. 2005). However, we note several contradictory reports, including the suggestion that in zebrafish, aortic endothelial cells may not directly give rise to definitive HSCs, but rather, HSCs may emerge from the sub-aortic mesenchyme (Kissa et al. 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Throughout development and adult life the vasculature exhibits a remarkably dynamic capacity for growth and repair. The vasculature also plays a pivotal role in the execution of other diverse biologic processes, such as the provisioning of early hematopoietic stem cells during embryonic development or the regulation of vascular tone and blood pressure. Adding to this importance, from an anatomical perspective, the vasculature is clearly an omnipresent organ, with few areas of the body that it does not penetrate. Given these impressive characteristics, it is perhaps to be expected that the vasculature should require, or at least be associated with, a ready supply of stem and progenitor cells. However, somewhat surprisingly, it is only now just beginning to be broadly appreciated that the vasculature plays host to a range of vessel-resident stem and progenitor cells. The possibility that these vessel-resident cells are implicated in processes as diverse as tumor vascularization and adaptive vascular remodeling appears likely, and several exciting avenues for clinical translation are already under investigation. This review explores the various stem and progenitor cell populations that are resident in the microvasculature, endothelium, and vessel walls and vessel-resident cells capable of phenotypic transformation.
    Stem Cell Research 02/2009; 2(1):2-15. DOI:10.1016/j.scr.2008.05.005 · 3.91 Impact Factor