Circulating Endothelial Progenitor Cells Are Up-Regulated in a Mouse Model of Endometriosis

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.

Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions

“…Besides angiogenesis, vascularization of endometriotic lesions also involves vasculogenesis, which is defined as de novo formation of microvessels from circulating endothelial progenitor cells [41][42][43]. Although not further analyzed in the present study, the suppression of this process may have been an additional mechanism contributing to the reduced functional capillary density of endometriotic lesions in quinalizarin-treated animals.…”

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

“…13 Besides, we and others have recently demonstrated that the vascularization of endometriotic lesions also involves vasculogenesis [ie, the de novo formation of blood vessels from circulating bone marrowederived endothelial progenitor cells (EPCs), which home to the lesions and are incorporated into the microvascular endothelium]. 14,15 This observation not only adds a novel biological process to the complex pathophysiology of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 endometriosis, but also offers the possibility to develop novel EPC-based approaches for the future diagnosis and therapy of the disease. A major prerequisite to achieve this goal is the detailed knowledge of the mechanisms that regulate vasculogenesis in endometriosis.…”

Sequential Observation of Implanted Endometriosis by Laparoscopy in Rats: Correlation Between the Prevalence Rate and the Estrous Cycle

“…Therefore, mice or rats were used as the experimental model, although no spontaneous endometriosis has been developed in these animals. In mice, endometriosis has been induced by the implantation of minced uterine tissue (5,6). An endometriotic implant model in rats has often been used to evaluate the effect of drugs and functional food having pharmacological action (7 -10).…”