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

ObjectiveTo study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation.DesignProspective experimental animal study.SettingUniversity 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.