Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium and endothelium. We investigated the nature of bone marrow-derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing an mTert-GFP or chicken β-actin-GFP reporter. mTert-GFP is a telomerase marker identifying haematopoietic stem cells in the bone marrow, and subpopulations of epithelial, endothelial and immune cells in the endometrium. Chicken β-actin-GFP is a ubiquitous reporter previously used to identify bone marrow-derived cells in the endometrium.
Confocal fluorescence microscopy for GFP and markers of endometrial and immune cells was used to characterise bone marrow-derived cells in the endometrium of transplant recipients. Recipients investigated/time post transplant: 5 mTert-GFP at 16-23 weeks; 6 chicken β-actin-GFP at 4 months; 8 chicken β-actin-GFP at 10 months. The number of stromal, epithelial and endothelial cells examined exceeded previous studies reporting bone marrow-derived endometrium.
No evidence of GFP+ bone marrow-derived stroma, epithelium or endothelium was observed in the endometrium of mTert-GFP or chicken β-actin-GFP recipients. All GFP+ cells detected in the endometrium of were immune cells expressing the pan leukocyte marker CD45, including CD3+ T cells and F4/80+ macrophages. Further examination of the chicken β-actin-GFP transplant model revealed that bone marrow-derived F4/80+ macrophages immunostained weakly for CD45. These macrophages were abundant in the stroma, infiltrated the epithelial and vascular compartments, and could easily be mistaken for bone marrow-derived endometrial cells if CD45 immunostaining and imaging protocols were suboptimal
We conclude that previous reports of bone marrow-derived endometrial stroma, epithelium and endothelium involve the misidentification of infiltrating immune cells, most likely macrophages. Resolving this issue is important, as the belief that bone marrow stem cells contribute directly to endometrial regeneration is shaping therapies designed regenerate endometrium in Asherman’s syndrome, and to control aberrant endometrial growth in endometriosis.