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RESEARCH PRODUCT

Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

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description

Objective To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation. Design Prospective experimental animal study. Setting University research laboratories. Animal(s) β-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice. Intervention(s) The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP + cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4 − BM-MAPCs), BMDC hypoblast-like stem cells (mOct4 + BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice. Main Outcome Measure(s) Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis. Result(s) After 12 weeks, histologic analysis revealed that uteri of mice with mOct4 − BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4 + BM-HypoSCs. The percentage of engrafted GFP + cells ranged from 0.13%–4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL + cells were increased in the EPCs and mOct4 + BM-HypoSCs groups. Conclusion(s) Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4 + BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4 − BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration.