© 2001 American Heart Association, Inc.
Letter to the Editor |
Contribution of Endothelial Cells of Hematopoietic Origin to Blood Vessel Formation
University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
eberhard.gunsilius{at}uibk.ac.at
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Introduction |
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To the Editor:
Crosby et al1 noted in their report that the recruitment of bone marrow–derived endothelial progenitor cells to newly forming blood vessels might have been hitherto overlooked. Postulated already a century ago,2 there is now ample evidence for a close association between blood progenitor cells and angiogenesis3 and the existence of a hemangioblastic progenitor capable of generating blood cells as well as endothelial cells.4 5 6 Also, the integration of bone marrow–derived endothelial cells or their progenitors into sites of neoangiogenesis is well-known.7 8 9 Their view that bone marrow–derived endothelial cells do not contribute substantially to the endothelium of blood vessels in stable adult tissue is equivocal. Endothelial cells are among those exhibiting the lowest replication level in the body with only 0.01% cells engaged in cell division at any time.10 Nevertheless, vascular endothelial cells that are lost from the vessel intima through necrosis or apoptosis must be replaced (maintenance angiogenesis). We are not aware of data showing that maintenance angiogenesis occurs through proliferation of adjacent endothelial cells. Thus, most likely, bone marrow–derived endothelial cells contribute to this maintenance angiogenesis.11
Vascular endothelial growth factor (VEGF) can mobilize endothelial cells or their progenitors from the bone marrow,9 and the delivery of VEGF to subjects may be deleterious.12 13 Hypoxia can also launch mobilization of endothelial precursor cells from the bone marrow, as hematopoietic cytokines (granulocyte/macrophage colony-stimulating factor) can do.14 Malignant tumor growth results in hypoxia within the neoplastic tissue, potentially mobilizing bone marrow–derived endothelial cells as well in a paracrine fashion, thus contributing to the sprouting of new tumor vessels. Moreover, cytokines accelerating hematopoietic recovery after myelotoxic chemotherapy might also promote the growth of tumor vessels by recruiting endothelial cells from the bone marrow, an issue that deserves critical evaluation.
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References |
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1. Crosby JR, Kaminski WE, Schatteman G, Martin PJ, Raines EW, Seifert RA, Bowen-Pope DF. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res. 2000;87:728–730.
2. His W. Lecithoblast und Angioblast der Wirbelthiere. Abhandl KS Ges Wiss Math Phys. 1900;22:171. Monograph.
3. Takakura N, Watanabe T, Suenobu S, Yamada Y, Noda T, Ito Y, Satake M, Suda T. A role for hematopoietic stem cells in promoting angiogenesis. Cell. 2000;102:199–209.
4. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376:62–66.
5. Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G. A common precursor for hematopoietic and endothelial cells. Development. 1998;125:725–732.
6. Green AR. Haemangioblast origin of chronic myeloid leukaemia? Lancet. 2000;355:1659–1660.
7. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999;85:221–228.
8. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–967.
9. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18:3964–3972.
10. Ortega N, Hutchings H, Plouet J. Signal relays in the VEGF system. Front Biosci. 1999;4:D141–D152.
11. Gunsilius E, Duba HC, Petzer AL, Kähler CM, Grünewald K, Stockhammer G, Gabl C, Dirnhofer S, Clausen J, Gastl G. Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet. 2000;355:1688–1691.
12. Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium: deleterious effects of unregulated expression. Circulation. 2000;102:898–901.
13. Carmeliet P. VEGF gene therapy: stimulating angiogenesis or angioma-genesis? Nat Med. 2000;6:1102–1103.
14. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5:434–438.>
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