Abstract
BackgroundIntrauterine adhesion (IUA) is a common uterine cavity disease which can be caused by mechanical damage that may eventually lead to infertility and pregnancy abnormalities. Since the effect of therapeutic drugs appears disappointing, cell therapy has emerged as an alternative choice for endometrium regeneration. The aim of this study is to investigate whether the combination of hydrogel Pluronic F-127 (PF-127), Vitamin C (Vc), and a bone marrow stromal cell (BMSC) mixture could be a feasible strategy to improve the endometrial regeneration in a mechanical damage model of IUA in rats.MethodsFirstly, PF-127 cytotoxicity and the effect of Vc was tested in vitro using the Annexin V/propidium iodide (PI) apoptosis test, cell count kit (CCK) growth test, and enzyme-linked immunosorbent assay (ELISA). For the establishment of the rat IUA model, a 2-mm transverse incision in the uterus was prepared at the upper end, and 1.5- to 2.0-cm endometrial damage was scraped. Rats were randomly assigned to five groups to investigate the combined strategy on IUA uterine regeneration: a sham group, an IUA control group, an IUA BMSC encapsulated in PF-127 plus Vc group, an IUA BMSC plus Vc group, and an IUA PF-127 plus Vc group. A cell mixture was injected into the uterine horn while making the IUA model. Eight weeks after cell transplantation, the rats were sacrificed and the uterine was dissected for analysis. Endometrial thickness, gland number, fibrosis area, and the expression of marker proteins for endometrial membrane were examined by hematoxylin and eosin staining, Masson’s staining, and immunohistochemistry.ResultsVc promoted the survival and health of PF-127-encapsulated BMSCs in vitro. When this combination was transplanted in vivo, the endometrium showed better restoration as the endometrium membrane became thicker and had more glands and less fibrosis areas. The expression of cytokeratin, von Willebrand Factor (vWF), was also restored. The proinflammatory cytokine interleukin-1β (IL-1β) was significantly lower compared with the control group.ConclusionsVc alleviates the cytotoxic effect of PF-127 and promotes cell survival and growth in rat BMSC encapsulation. Thus, a cell therapy strategy containing biomaterial scaffold, BMSCs and the modulatory factor Vc promotes the restoration of damaged IUA endometrium.
Highlights
Intrauterine adhesion (IUA) is a common uterine cavity disease which can be caused by mechanical damage that may eventually lead to infertility and pregnancy abnormalities
Isolation of bone marrow stromal cell (BMSC) from rats Rat BMSCs were derived from tibiae and femurs of 8-week-old Sprague-Dawley female rats by bone marrow aspiration following published methods [16]
As mesenchymal stromal cells express cluster of differentiation 29 (CD29) and CD90, but lack expression of CD34 and CD45 on the cell surface [17, 18], we sought to test the expression of these markers in our cultured BMSCs
Summary
Intrauterine adhesion (IUA) is a common uterine cavity disease which can be caused by mechanical damage that may eventually lead to infertility and pregnancy abnormalities. Since the effect of therapeutic drugs appears disappointing, cell therapy has emerged as an alternative choice for endometrium regeneration. The aim of this study is to investigate whether the combination of hydrogel Pluronic F-127 (PF-127), Vitamin C (Vc), and a bone marrow stromal cell (BMSC) mixture could be a feasible strategy to improve the endometrial regeneration in a mechanical damage model of IUA in rats. Several therapeutic drugs have been tried in an attempt to improve the regeneration of the endometrium Most of these efforts were less effective and, in most situations, the results were controversial due to a diverse treatment schedule, a different population, and different measurements [4, 5]. BMSCs have immune modulatory properties and can induce angiogenesis and tissue repair, which makes them suitable for diverse applications in regeneration medicine [7]
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