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Depletion of Endothelial Progenitor Cells May Link Pulmonary Fibrosis and Pulmonary Hypertension

We enjoyed reading the letter by Fadini and colleagues regarding the potential role of endothelial progenitor cells (EPCs) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). As noted in our article (1), we wholeheartedly agree with the need for further studies that explore the new and rapidly evolving field of EPCs and the biology of other circulating progenitor cells in lung disease. As briefly noted in our article (1), however, we still have much to learn about the nature of EPCs and their measurement, and need to remain cautious in data interpretation. This is based on extensive studies by several laboratories, most notably the work of Ingram, Yoder, and others, in which critical questions have been raised regarding the fundamental definition of EPCs by antibody phenotyping with markers of cellular differentiation (CD) (2–5). For example, recent work clearly demonstrates that not all circulating cells which are CD133⁺/CD34⁺/KDR⁺ cells reflect endothelial lineage, and may be hematopoietic precursors (such as "angiogenic macrophages"), especially when CD45 or CD14 positive subpopulations are not excluded (3, 4). Importantly, functional studies can fail to demonstrate high proliferative potential or maturation to endothelial cells in vitro. We look forward to further studies that help to better define and characterize the biology of circulating progenitor cells and their potential therapeutic roles, especially in the setting of pulmonary vascular disease.

Bernard Thébaud

University of Alberta, Edmonton, Alberta, Canada

Steven Abman

University of Colorado School of Medicine and The Children's Hospital, Denver, Colorado

FOOTNOTES

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

Nathan and colleagues declined to respond to the letter by Fadini and colleagues.

REFERENCES

1. Thébaud B, Abman SH. Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med 2007;175:978–985.[Abstract/Free Full Text]
2. Schatteman GC, Dunnwald M, Jiao C. Biology of bone marrow-derived endothelial cell precursors. Am J Physiol Heart Circ Physiol 2007;292:H1–H18.[Abstract/Free Full Text]
3. Yoder MC, Mead LE, Prater D, Krier JR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT, Ingram DA. Redefining EPC via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 2007;109:1801–1809.[Abstract/Free Full Text]
4. Case J, Mead LE, Bessler WK, Prater D, White HA, Saadatzadeh MR, Bhavsar JR, Yoder MC, Haneline LS, Ingram DA. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol 2007;35:1109–1118.[CrossRef][Medline]
5. Luttun A, Verfaille CM. Will the real EPC please stand up? Blood 2007;109:1795–1796.[Free Full Text]

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