Regulatory T (Treg) cells play a key role in the regulation of autoimmunity and transplantation. Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has a potential to restore ovarian dysfunction associated with premature ovarian failure (POF), while the exact function of the Treg cells in the transplantation still needs to be further investigated. In this study, hPMSCs were intravenously injected into POF mice following zona pellucida glycoprotein 3 (pZP3) treatment. Ovarian function was measured by analyzing estrous cycle, folliculogenesis, and hormone secretion, also, with the detection of apoptotic granular cells (GCs) in ovarian tissues. To determine whether immune response is involved in the regulation of ovarian function change, the population of Treg cell populations and expression of associated cytokines, for example, transforming growth factor β (TGF-β) and interferon γ (IFN-γ) were measured. After hPMSCs transplantation, the injured ovarian function is significantly improved. Also, the pZP3-treatment-induced apoptotic GCs were significantly decreased as compared with the POF mice. The transplantation of hPMSCs significantly increased the population of Treg cells which was inhibited by pZP3 treatment. The decrease in TGF-β and increase in IFN-γ in serum caused by pZP3 treatment have been reversed following hPMSCs transplantation. These findings strongly suggest that the recovery of ovarian function in POF mice is mediated via the regulation of Treg cells and production of associated cytokines following hPMSCs transplantation.

BackgroundHuman placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation.MethodsThe inhibitor of PI3K/Akt was administered to observe its effect on ovarian function recovery and immune regulation. Serum levels of estradiol (E2), follicle stimulation hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)) and anti-Zona pellucida antibody (AZPAb) were measured by ELISA to evaluate ovarian function. The morphological changes of ovaries were observed by HE staining. Apoptosis of granular cells (GCs) was determined by detecting the expression of capase-3. Expression of p-Akt protein was detected by immunohistochemistry and western blot assay in ovarian tissues. The MTT assay was performed to assess GC proliferation. GC apoptosis was performed using flow cytometry analysis. Percentages of Th17, Tc17 and Treg cells were detected by flow cytometry. Expression of interleukin (IL)-17 in serum was measured by ELISA.ResultsLY294002 administration decreased serum levels of E2 and AMH, while the levels of FSH, LH and AZPAb in serum were increased compared with mice in the hPMSC transplantation group. The ovarian morphology presented as atrophy and fibrosis, with functional follicles exhausted. The expression of p-Akt in ovarian tissue was significantly decreased. Also, LY294002 administration significantly decreased proliferation and increased cell apoptosis in GCs, and for immune factors the ratios of Th17/Tc17 and Th17/Treg cells were significantly increased, as well as the serum levels of IL-17.ConclusionsOur data suggest that the PI3K/Akt signal pathway is involved in the recovery of ovarian function by changing the ratios of Th17/ Tc17 and Th17/Treg cells in POF mice following hPMSC transplantation.

B7-H3 has been detected in different cancers and correlated to tumor progression and outcome in cancer patients. In this study, we investigated the expression of B7-H3 in tissues and cells of primary hepatocellular carcinoma (PHC) patients. The research showed that B7-H3 is aberrantly expressed in PHC tissues and cells, and its high expression on HepG2 cells significantly promotes cell proliferation, adhesion, migration, and invasion capacity; moreover, it inhibits the proliferation of CD8(+) T cells. Thus, B7-H3 may have a critical role in PHC and it may enhance tumor escape from the immune surveillance of CD8(+) T cells.

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Silk fibroin of the silkworm Bombyx mori has been studied extensively, while the research on Antheraea pernyi silk fibroin (A. pernyi SF) in biomaterials is only at an early stage. In this study, the attachment, morphology, growth and phenotype of human bone marrow derived mesenchymal stem cells (hBMSCs) cultured on the regenerated A. pernyi SF films were studied in vitro. The results indicated that the attachment of hBMSCs on the regenerated A. pernyi SF films was almost the same as that on the collagen films. MTT and cell counting analyses demonstrated that the growth of hBMSCs on the regenerated A. pernyi SF films was better than that on controls. Moreover, electron scanning microscopy and fluorescence-activated cell sorting assays showed that the regenerated A. pernyi SF supported hBMSCs growth and functional maintenance compared with the controls. These data suggest that the regenerated A. pernyi SF, like Bombyx mori silk fibroin (B. mori SF) and collagen, can support hBMSCs attachment, growth and phenotypic maintenance, and has better biocompatibilities for hBMSCs in vitro culture.

Mesenchymal stem cells (MSCs) play important roles in tissue regeneration due to their self-renewal, multilineage differentiation and immunosuppression abilities. MSCs can be isolated from various kinds of tissue, such as umbilical cord, cord blood and placenta. Human placenta mesenchymal stem cells (hPMSCs) possess stronger immunosuppressive properties, such as the ability to inhibit T-cell activation and proliferation, than human bone marrow MSCs. We have investigated that the roles of the programmed death ligands 1 and 2 (PDL1 and PDL2) in hPMSC adhesion, migration and immunosuppression were investigated. PDL1 and PDL2 were highly expressed by hPMSCs. Knockdown of PDL1 and/or PDL2 by siRNA increased hPMSC adhesion, but greatly decreasing migration. PDL1 and PDL2 expressed on hPMSCs inhibited T-cell proliferation by arresting the cell cycle. Knockdown of PDL1 and/or PDL2 in hPMSCs, however, had no effect on the expression of CD69, a T-cell early activation marker found on both CD4(+) and CD8(+) T-cell subsets. In summary, the roles of the negative co-stimulators PDL1 and PDL2 is on the adhesion, migration and immunosuppression of hPMSCs. These findings may be useful regarding the potential use of hPMSCs in clinical cell.

BackgroundUterine fibroids (UFs) are the most common form of sex steroid hormone-dependent benign tumours that grow in the walls of the uterus. Several observational studies have examined the association between obesity and the risk of UFs, but findings are inconsistent. The objective of this systematic review and meta-analysis is to further examine the association of obesity with the risk/prevalence of UFs.MethodsA literature search was performed in three databases (PubMed, EMBASE and Web of Science) from 1 January 1992 to 30 May 2020. We used random-effect models to calculate the pooled ORs with corresponding 95% CIs. Additionally, we performed a dose–response meta-analysis to analyse the effect of body mass index (BMI), weight change since age 18, waist-to-hip ratio and waist circumference on the risk/prevalence of UFs.ResultsA total of 22 articles, covering 24 studies including 325 899 participants and 19 593 cases, were selected based on our inclusion criteria. We found a positive association between obesity and the risk/prevalence of UFs (OR, 1.19; 95% CI, 1.09 to 1.29). Among participants with the highest BMI, the pooled OR was 1.19 (1.09 to 1.31) when compared to participants with normal BMI. For weight change since age 18, the pooled OR (95% CI) of UFs was 1.26 (1.12 to 1.42) among the highest change group when compared with no change. Additionally, our meta-analysis indicated the relationship of BMI with risk of UFs to be an inverse J-shaped pattern.ConclusionsThe results of this meta-analysis suggest that obesity may increase the risk/prevalence of UFs, and the association is non-linear.

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