Xueyun Liang

Astrocytic function imbalance is a key factor affecting cerebral ischemia rehabilitation. Mesenchymal stem cells have therapeutic potential for cerebral ischemia, but their mechanisms remain unclear. This study explored how placental mesenchymal stem cells pro-mote astrocytes towards the A2 phenotype, which benefits the repair of cerebral ischemia injury. We established the animal model of middle cerebral artery ischemia/reperfusion and an in vitro interleukin-1β-treated astrocyte inflammation model and utilized neuro-logical function assessment, 2,3,5-triphenyltetrazolium chloride staining, immunofluorescence staining, Western blotting and other methods to evaluate the impact and associated mechanisms of transplanting placental mesenchymal stem cells into rats with cerebral ischemia–reperfusion injuries. The results demonstrated that transplantation of placental mesenchymal stem cells ameliorated neurological dysfunction and histopathological damage, alleviated neuroinflammation and enhanced neurotrophic factor levels, promoted the polarization of interleukin-1β-treated astrocytes toward the A2 phenotype, and suppressed the abundance of core mediators within the cerebral TGF β1/Smad signaling cascade in ischemia/reperfusion model. Collectively, placental mesenchymal stem cell grafting facilitates the polarization of cerebral astrocytes toward the protective A2 phenotype, presumably by regulating the TGF β1/Smad signaling cascade in ischemic brain injury.

Premature ovarian insufficiency (POI) is a common clinical problem, however, there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. Female Sprague–Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. VCD significantly damaged rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs markedly suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1β and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors by phenotypic changes in macrophages. Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function.

Background: The mechanism by which MSC-CM protects neuronal cells against ischemic injury remains to be elucidated. In this study, we aimed to clarify the protective effect of umbilical cord-derived mesenchymal stem cell conditioned medium (UC-MSC-CM) on neuronal oxidative injury and its potential mechanism. Methods and Results: Neuronal oxidative damage was mimicked by H2O2 treatment of the HT22 cell line. The numbers of cleaved-Caspase-3-positive cells and protein expression of Caspase-9 induced by H2O2 treatment were decreased by UC-MSC-CM treatment. Furthermore, SOD protein expression was increased in the MSC-CM group compared with that in the H2O2 group. The H2O2-induced TRPM2-like currents in HT22 cells were attenuated by MSC-CM treatment. In addition, H2O2 treatment downregulated the expression of p-JNK protein in HT22 cells, and this the downward trend was reversed by incubation with MSC-CM. Conclusions: UC-MSC-CM protects neurons against oxidative injury, possibly by inhibiting activation of TRPM2 and the JNK signaling pathway.

In this study, we aimed to clarify the protective effect of umbilical cord-derived mesenchymal stem cell conditioned medium (UC-MSC-CM) on neuronal oxidative injury and its potential mechanism. Neuronal oxidative damage was mimicked by H2O2 treatment of the HT22 cell line. Immunofluorescence staining was used to analyze the expression of cleaved Caspase3 and TRPM2. Cytotropic factors secreted by UC-MSCs were analyzed by enzyme-linked immunosorbent assay. Whole-cell patch clamping was used to detect TRPM2-like currents. Western blotting was utilized to analyze the protein levels of SOD, p-ERK1/2, p-JNK1/2/3 and cleaved-Caspase-9. The number of cleaved-Caspase-3-positive cells and protein expression of Caspase-9 induced by H2O2 treatment were decreased by UC-MSC-CM treatment. Furthermore, SOD protein expression was increased in the MSC-CM group compared with that in the H2O2 group. The H2O2-induced TRPM2-like currents in HT22 cells were attenuated by MSC-CM treatment. In addition, H2O2 treatment downregulated the expression of p-JNK protein in HT22 cells, and this the downward trend was reversed by incubation with MSC-CM. Thus, we showed that UC-MSC-CM protects neurons against oxidative injury, possibly by inhibiting activation of TRPM2 and the JNK signaling pathway.

Mesenchymal stem cells (MSCs) capable of tumour topotaxis have been served as cellular vehicles to deliver anti-tumour agents. As cellular components of the tumour microenvironment, MSCs also affect tumour progression. However, the tumour transformation-related genes of MSCs remain unclear since either tumorigenic or tumour suppressor effects within these cells have been researched. Hence, we aimed to identify potential biomarkers indicative of tumorigenic risk by RNA-seq analysis of human placenta tissue-derived MSCs (hPTMSCs) exposed to the carcinogenic agent, 3-methylcholanthrene (3-MC). Twenty-nine tumour transformation-related genes and three pluripotency-related genes were appraised as differentially expressed genes (DEGs) in hPTMSCs. Overexpression of sfrp1 led to reduced cell viability, migration, and colony formation in A549. In contrast, the overexpression of ptgs2 exerted the opposite effect. These results indicate that A549 cells with high ptgs2 expression but low sfrp1 expression may have a more potential tumorigenic capacity. Taken together, this study suggests that ptgs2 and sfrp1 may be tumorigenic risk genes.

Background Mesenchymal stem cells (MSCs) display tumour tropism and have been explored as cellular vehicles to deliver anti-cancer agents. As cellular components of the tumour microenvironment, MSCs also influence tumour progression. However, the tumour transformation-related genes of MSCs are not well understood since either oncogenic or tumour suppressor effects within these cells have been reported. Here, we aimed to identify potential biomarkers capable of tumorigenic risk by RNA-seq analysis of human placenta tissue-derived MSCs (hPTMSCs) exposed to the carcinogenic agent 3-methylcholanthrene (3-MC). Results Twenty-nine tumour transformation-related genes and three pluripotency-related genes were identified as differentially expressed genes (DEGs) in hPTMSCs. Importantly, SFRP1 and PTGS2 were further identified as tumour suppressors and oncogenes in hPTMSCs, respectively. The overexpression of SFRP1 and PTGS2 was positively correlated with the expression of the pluripotent markers OCT4, CMYC and NANOG in the human lung adenocarcinoma cell line A549, and the low expression of SFRP1 and PTGS2 was inversely correlated with the expression of the pluripotent markers SOX2, OCT4 and NANOG in hPTMSCs. Interestingly, overexpression of SFRP1 led to reduced cell viability, colony formation and migration of A549 cells. In contrast, the ectopic expression of PTGS2 exerted the opposite effect. Conclusions These results indicate that hPTMSCs with high PTGS2 expression but low SFRP1 expression may have more potential tumorigenic capacity. Taken together, this study suggests that PTGS2 and SFRP1 may be valuable biomarkers for quality and safety control of hPTMSC preparations in clinical applications, which warrants further study.