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 agb3, 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 a messenger RNA (mRNA) and interleukin (IL)-1bmRNA, 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.

Human CD133+ bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome

“…In the present study, we show that human SPIOs-labeled CD133 þ cells engrafted around blood vessels, a location that has previously been described as the endometrial stem cell niche (5,7,16,36). The signals driving the migration and homing of endothelial progenitor cells to injured endothelium sites or extravascular tissue are largely unknown (37).…”

“…There is additional evidence that murine bone marrow mesenchymal stem cells contribute to endometrial restoration in rodents (14)(15)(16)27), and bone marrow injection has been shown to promote endometrial regeneration and restore fertility in an AS model (15,17). In this work, our aim is to demonstrate that human CD133 þ BMDSC injection by intrauterine or systemic delivery could promote endometrial proliferation and the resulting reduction of fibrosis in a murine model of AS.…”

“…Common treatments include exogenous estrogen (E), low-dose aspirin, vaginal sildenafil citrate, pentoxifylline, vitamin E, L-arginine, and cytokines, although none of them have demonstrated promising clinical effectiveness (13). Murine models of AS have been generated (injecting anhydrous ethanol (14)(15)(16) or by mechanical trauma (17)) with the hope of exploring new treatment options.…”

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17&beta;-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

“…A recent study by Zhao et al showed a positive effect of bone marrow mesenchymal stem cells treatment on a rat model with thin endometrium. 23 Moreover, a collagen scaffold loaded with …”

Regenerative Medicine and Tissue Engineering in Reproductive Medicine

“…32 At the clinical level several studies suggest the possible application of stem cell therapies for Asherman syndrome, which causes endometrial destruction. [33][34][35][36] Our group is also performing similar work, which has demonstrated the beneficial effect of BMDCs and their ability to home and to colonize murine endometrium, where they engraft mainly around the vascular space (unpublished data). Four months later endometrial thickness, morphology, and vascularity improved and a pregnancy was successfully obtained after in vitro fertilization treatment.…”