Uterine Infusion With Bone Marrow Mesenchymal Stem Cells Improves Endometrium Thickness in a Rat Model of Thin Endometrium

Abstract

Bone marrow mesenchymal stem cells (BMSCs) show multidirectional differentiation and possess immunoregulatory properties. Although transplantation of BMSCs has a therapeutic effect on many diseases, it is unclear whether BMSC transplantation can be used as a therapy for a thin endometrium. To explore whether transplantation of BMSCs directly into the uterine cavity can improve endometrium thickness, a thin endometrium rat model was established by infusing ethanol into the uterine cavity. In all, 48 rats with thin endometrium and 24 normal rats were divided into 3 groups: (1) normal group, (2) experimental group transplanted with BMSCs into uterine cavity, and (3) control group transplanted with saline into the uterine cavity. The morphology of the endometrium, the regeneration and receptivity of the endometrium, and the mechanisms involved in BMSC therapy were subsequently analyzed by hematoxylin and eosin staining, Western blot analysis, and reverse transcription-polymerase chain reaction throughout an observation period of 3 estrus cycles. The rats in the experimental group had a significantly thicker endometrial lining and exhibited higher expression of cytokeratin, vimentin, integrin αγβ3, and leukaemia inhibitor factor (LIF) than that of the control group (P < .05). Bromodeoxyuridine -positive cells were detected in the endometrium after BMSC transplantation. Some proinflammatory cytokines, such as tumor necrosis factor α messenger RNA (mRNA) and interleukin (IL)-1βmRNA, were significantly downregulated, and anti-inflammatory cytokines, such as basic fibroblast growth factor (bFGF) mRNA and IL-6mRNA, were significantly upregulated in the experimental group compared to the control group (P < .05). In conclusion, BMSCs improved endometrium thickness, probably via their migration and immunomodulatory properties. Uterine perfusion with BMSCs represents a promising new tool for the currently intractable problem of an inadequate, thin endometrium.