Circulating endothelial progenitor cells are up-regulated in a mouse model of endometriosis

Christian M. Becker, Paul Beaudry, Tae Funakoshi, Ofra Benny, Alexander Zaslavsky, David Zurakowski, Judah Folkman, Robert J. D'Amato, Sandra Ryeom

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Endometriosis is a debilitating disease characterized by the growth of ectopic endometrial tissue. It is widely accepted that angiogenesis plays an integral part in the establishment and growth of endometriotic lesions. Recent data from a variety of angiogenesis-dependent diseases suggest a critical role of bone marrow-derived endothelial progenitor cells (EPCs) in neovascularization. In this study we examined the blood levels of EPCs and mature circulating endothelial cells in a mouse model of surgically induced endometriosis. Fluorescence-activated cell sorting analysis revealed elevated levels of EPCs in the blood of mice with endometriosis compared with control subject that underwent a sham operation. EPC concentrations positively correlated with the amount of endometriotic tissue and peaked 1 to 4 days after induction of disease. In a green fluorescent protein bone marrow transplant experiment we found green fluorescent protein-positive endothelial cells incorporated into endometriotic lesions but not eutopic endometrium, as revealed by flow cytometry and immunohistochemistry. Finally, treatment of endometriosis-bearing mice with the angiogenesis inhibitor Lodamin, an oral nontoxic formulation of TNP-470, significantly decreased EPC levels while suppressing lesion growth. Taken together, our data indicate an important role for bone marrow-derived endothelial cells in the pathogenesis of endometriosis and support the potential clinical use of anti-angiogenic therapy as a novel treatment modality for this disease.

Original languageAmerican English
Pages (from-to)1782-1791
Number of pages10
JournalAmerican Journal of Pathology
Volume178
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Endometriosis Millennium Fund from the Royal College of Obstetrics and Gynaecology, United Kingdom ; an MRC New Investigator Award ( G0601458 to C.M.B.); the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health's NIHR Biomedical Research Centres scheme (C.M.B.); and a grant from the Sydney Swensrud Foundation (R.J.D.). C.M.B. was supported by a Postdoctoral Research Exchange Fellowship from the Max Kade Foundation . P.B. was supported by an Alberta Heritage Foundation for Medical Research Clinical Fellowship . S.R. was supported by the Garrett B. Smith Foundation .

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