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• W2976335638 abstract "Bone marrow-derived progenitor cells contribute to various nonhematopoietic cell populations in the endometrium including decidual stromal cells (DSCs). However, the exact BM lineage of BM-derived DSCs is unknown. Our objective was to explore the dynamics of circulating bone marrow mesenchymal stem cells (BM-MSCs) during pregnancy and investigate whether BM-MSCs may be the origin of BM-derived DSCs. Animal Study. BM cells from whole body GFP or GFP under regulation of Hoxa11 promoter (Hoxa11-GFP) transgenic mice were used for BM transplantation (BMT) into wild-type C57BL6/J syngeneic females following established 5-FU based submyeloablation regimen (∼45% chimerism). Hoxa11 expression in the BM is restricted to MSCs and is not expressed in hematopoietic cells, allowing in-vivo tracking of BM-MSCs. Following 1-month recovery, mice were mated with proven males. Multicolor flow cytometry was performed on peripheral blood, BM and uterus/decidua of non-pregnant, and pregnant mice on E5.5 and E9.5, timing of peak BMDCs recruitment to the uterus. Live cells were gated on Sca1+ and Lin- to identify stem cell populations and further divided into MSCs (Sca1+/CD45-/Lin-) and hematopoietic stem cells (HSCs) (Sca1+/CD45+/Lin-). Extracted BM cells were cultured in MSC expansion media, and characterized by flow cytometry, trilineage MSC differentiation, and decidualization assays. Flow cytometry analysis showed that circulating MSCs were increased in pregnant mice from 0.002% in nonpregnant to 0.007% on E5.5, and further increased to 0.014% on E9.5 (∼7-fold compared to nonpregnant, p<0.01, n=5/group). In contrast, circulating HSCs remain unchanged from nonpregnant through E9.5 (0.10% vs. 0.11%), as did BM MSCs and HSCs. In the Hoxa11-GFP BMT model, BM-derived Hoxa11+GFP+ cells were detected in the E9.5 pregnant decidua (0.25±0.4% of total cells) and were CD45- by flow cytometry analysis, indicating that BM-MSCs are a likely origin of BM-derived DSCs. In-vitro, we cultured BM cells from GFP+ BMT recipients and analyzed P-2 cells for MSC characteristics. BM GFP+ cells were plastic-adherent and grew in MSC expansion media. Flow cytometry demonstrated that 9.5% of GFP+ cells were triple-positive for MSC markers Sca-1+CD29+CD44+ and CD45-. Cultured BM GFP+ cells had trilineage differentiation ability to adipogenic, osteogenic and chondrogenic lineages, confirming their MSC characteristics. Moreover, cultured BM cells showed characteristic decidual morphological changes in response decidualization stimuli, most prominent in the combined cAMP+17-MPA treatment group. In addition, expression of decidual prolactin prl8a2 mRNA was upregulated 10-fold on culture day 8 and 14 in the BM cells subjected to decidualization treatment vs. control (p<0.01). These data show that BM-MSCs are increasingly mobilized to the circulation during murine pregnancy, are able to undergo decidualization in-vitro, and are a source of Hoxa11+ nonhematopoietic decidual cells in pregnancy. These suggest that BM-MSCs play an important previously unrecognized role in pregnancy." @default.
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• W2976335638 date "2019-09-01" @default.
• W2976335638 modified "2023-10-18" @default.
• W2976335638 title "Bone marrow mesenchymal stem cells are mobilized to the circulation during pregnancy and are a source of decidual stromal cells" @default.
• W2976335638 doi "https://doi.org/10.1016/j.fertnstert.2019.07.383" @default.
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