Key Endothelial Signals Required for Hematopoietic Recovery

Wilmot Cancer Center and Endocrine Division, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 693, Rochester, NY 14642, USA.
Cell stem cell (Impact Factor: 22.27). 04/2009; 4(3):187-8. DOI: 10.1016/j.stem.2009.02.005
Source: PubMed


In this issue of Cell Stem Cell, Hooper et al. (2009) use a combination of immunohistochemistry and flow cytometry to characterize the bone marrow vasculature both before and after injury. The authors demonstrate that recovery of normal hematopoiesis after myelosuppressive insult is dependent upon endothelial VEGFR2.

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    • "Many groups have helped to characterise the bone marrow stem cell niche(s) (Adams et al. 2007, Frisch et al. 2008, Porter and Calvi 2008, Raymond et al. 2009) and, in terms of regulation, have shown that it occurs through cells within the bone marrow microenvironment, an environment that includes, for example, the osteoblasts (Calvi et al. 2003), osteoclasts (Kollet et al. 2006), and endothelial cells (Porter and Calvi 2009), and is likely maintained through cell-cell and cell-extracellular matrix interactions. With respect to radiation injury specifically, some investigators have shown that the bone marrow stem cell niche is relatively hypoxic (Parmar et al. 2007) and since the stem cells appear to exist in a quiescent or very slowly cycling state (Harrison and Astle 1982, Schaniel and Moore 2009) they are therefore, relatively radio-resistant. "
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    International Journal of Radiation Biology 03/2011; 87(8):851-68. DOI:10.3109/09553002.2011.560996 · 1.69 Impact Factor
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    ABSTRACT: Pancytopenia is a major cause of morbidity in acute myeloid leukemia (AML), yet its cause is unclear. Normal osteoblastic cells have been shown to support hematopoiesis. To define the effects of leukemia on osteoblastic cells, we used an immunocompetent murine model of AML. Leukemic mice had inhibition of osteoblastic cells, with decreased serum levels of the bone formation marker osteocalcin. Osteoprogenitor cells and endosteal-lining osteopontin(+) cells were reduced, and osteocalcin mRNA in CD45(-) marrow cells was diminished. This resulted in severe loss of mineralized bone. Osteoclasts were only transiently increased without significant increases in bone resorption, and their inhibition only partially rescued leukemia-induced bone loss. In vitro data suggested that a leukemia-derived secreted factor inhibited osteoblastic cells. Because the chemokine CCL-3 was recently reported to inhibit osteoblastic function in myeloma, we tested its expression in our model and in AML patients. Consistent with its potential novel role in leukemic-dependent bone loss, CCL-3 mRNA was significantly increased in malignant marrow cells from leukemic mice and from samples from AML patients. Based on these results, we propose that therapeutic mitigation of leukemia-induced uncoupling of osteoblastic and osteoclastic cells may represent a novel approach to promote normal hematopoiesis in patients with myeloid neoplasms.
    Blood 09/2011; 119(2):540-50. DOI:10.1182/blood-2011-04-348151 · 10.45 Impact Factor
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    Z Yan · L Zeng · Z Li · H Zhang · W Chen · L Jia · C Chen · H Cheng · J Cao · K Xu ·
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    ABSTRACT: A hematopoietic deficit is a serious complication after hematopoietic stem cell transplantation. It has been shown that fetal blood-derived endothelial progenitor cells (EPCs) can promote hematopoietic reconstitution after transplantation. This study investigated whether EPCs from bone marrow (BM) of adult mice could promote hematopoietic reconstitution. Lethally irradiated BALB/c mice were administered BM cells or BM cells plus EPCs. The results showed that EPC-treated mice displayed accelerated recovery of peripheral blood white blood cells and reticulocytes. But the platelets were not significantly different with versus without EPCs. Accelerated recovery of BM sinusoidal vessels, promotion of stem cell implantation, and decreased adipocyte formation were associated with the mechanism. Systemic administration of anti-vascular endothelial cadherin antibody neutralized these effects significantly. These data showed that BM-derived EPC infusions augmented hematopoiesis suggesting a new approach to promote hematopoiesis.
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