The Bone Marrow Is a Long Term Source of Murine Endometrial Parenchymal Stromal Cells

Presentation Number: SUN-0038
Date of Presentation: June 22nd, 2014

Sara Sinha Morelli*, Pranela Rameshwar and Laura T Goldsmith
Rutgers - New Jersey Medical School, Newark, NJ

Abstract

Cyclic replenishment of all cellular compartments of the human endometrium is absolutely required for successful reproduction.  The mechanisms involved in cyclic endometrial regeneration, including the cellular source of regenerative endometrial cells, remain poorly understood.  The current studies tested the hypothesis that bone marrow (BM) cells give rise to mature, endometrial parenchymal stromal cells, the predominant endometrial structural cell type.

          A murine BM transplant model was used, in which BM cells harvested from transgenic mice which express Green Fluorescent Protein (GFP) were injected via tail vein into syngeneic immature female mice.  Five mice with successful hematopoietic reconstitution were sacrificed at 12 months post transplant and hysterectomy was performed.  Immunohistochemistry using specific anti-GFP and anti-vimentin (parenchymal stromal cell marker) antibodies was performed to enable localization and quantitation of BM-derived and parenchymal stromal cell types in uterine tissue sections of recipient mice.  Confocal laser microscopy was used to identify GFP-positive cells, vimentin-positive cells and fluorescently stained nuclei in endometrial stromal compartments.  BM-derived parenchymal stromal cells were identified as those which were co-positive for GFP and vimentin.

          The proportion of total endometrial stromal compartment cells which was BM-derived in each animal was 15.3% (369 GFP+cells/2411 total stromal compartment cells), 10.8% (332/3066), 16.2% (327/2021), 12.2% (364/2973) and 5.9% (238/4004) [12.1% ± 4.1% (mean ± SD), n=5 animals]. Parenchymal stromal cells (not other cell types) comprised 29.4% (708/2411), 27.9% (854/3066), 20.3% (410/2021), 31.6% (938/2973) and 28.6% (1144/4004) of total endometrial stromal compartment cells in each animal [27.6% ± 4.3%  (mean ± SD), n=5 animals].  The proportion of endometrial parenchymal stromal cells which was BM-derived in each animal was 15.7% (111/708), 14.9% (127/854), 21.2% (87/410), 13.0% (122/938) and 7.3% (83/1144) [14.4%  ± 5.0% (mean ± SD), n=5 animals].

          These data definitively demonstrate that bone marrow gives rise to a critical structural component of the endometrium, since bone marrow is a long term source of mature endometrial parenchymal stromal cells. These findings significantly advance understanding of the mechanisms responsible for endometrial regeneration and implicate a novel role for bone marrow-derived cells in treatment of disorders of endometrial function.

 

Nothing to Disclose: SSM, PR, LTG