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

Capsule:
The BMDCs might improve uterine tissue as a valuable source for endometrial restoration.

Authors:
Claudia Gil-Sanchis, Ph.D., Irene Cervelló, Ph.D., Satish Khurana, Ph.D., Amparo Faus, B.Sc., Catherine Verfaillie, M.D., Ph.D., Carlos Simón, M.D., Ph.D.

Volume 103, Issue 6, Pages 1596-1605

Abstract:

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.

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