Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency

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Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma

Asthma is a complicated lung disease, which has increased morbidity and mortality rates in worldwide. There is an overlap between asthma pathophysiology and mitochondrial dysfunction and MSCs may have regulatory effect on mitochondrial dysfunction and treats asthma. Therefore, immune-modulatory effect of MSCs and mitochondrial signaling pathways in asthma was studied.After culturing of MSCs and producing asthma animal model, the mice were treated with MSCs via IV via IT. BALf's eosinophil Counting, The levels of IL-4, −5, −13, −25, –33, INF-γ, Cys-LT, LTB4, LTC4, mitochondria genes expression of COX-1, COX-2, ND1, Nrf2, Cytb were measured and lung histopathological study were done.BALf's eosinophils, the levels of IL-4, −5, −13, −25, –33, LTB4, LTC4, Cys-LT, the mitochondria genes expression (COX-1, COX-2, Cytb and ND-1), perivascular and peribronchial inflammation, mucus hyper-production and hyperplasia of the goblet cell in pathological study were significantly decreased in MSCs-treated asthma mice and reverse trend was found about Nrf-2 gene expression, IFN-γ level and ratio of the INF-γ/IL-4.MSC therapy can control inflammation, immune-inflammatory factors in asthma and mitochondrial related genes, and prevent asthma immune-pathology.     

MSC derived EV loaded with miRNA-22 inhibits the inflammatory response and nerve function recovery after spinal cord injury in rats

Our previous research has found that miRNA-22 can inhibit the occurrence of pyroptosis by targeting GSDMD and decrease the production and release of inflammatory factors. In consideration of the therapeutic effects of mesenchymal stem cells (MSCs), MSCs-EV were loaded with miRNA-22 (EV-miRNA-22) to investigate the inhibitory effect of EV-miRNA-22 on the inflammatory response in SCI in rats in this study. LPS/Nigericin (LPS/NG) was used to induce pyroptosis in rat microglia in vitro. Propidium iodide (PI) staining was performed to observe cell permeability, lactate dehydrogenase (LDH) release assay was adopted to detect cytotoxicity, flow cytometry was conducted to detect pyroptosis level, immunofluorescence (IF) staining was utilized to observe the expression level of GSDMD (a key protein of pyroptosis), Western blot was performed to detect the expression of key proteins. For animal experiments, the T10 spinal cord of rats was clamped by aneurysm clip to construct the SCI model. BBB score, somatosensory evoked potential (SEP) and motor evoked potential (MEP) were performed to detect nerve function. HE staining and Nissl staining were used to detect spinal cord histopathology and nerve cell damage. EV-miRNA-22 could inhibit the occurrence of pyroptosis in microglia, suppress the cell membrane pore opening, and inhibit the release of inflammatory factors and the expression of GSDMD. In addition, EV-miRNA-22 showed higher pyroptosis-inhibiting ability than EV. Consequently, EV-miRNA-22 could inhibit the nerve function injury after SCI in rats, inhibit the level of inflammatory factors in the tissue and the activation of microglia. In this study, we found that miRNA-22-loaded MSCs-EV (EV-miRNA-22) could cooperate with EV to inhibit inflammatory response and nerve function repair after SCI.     

Reprogramming to a pluripotent state modifies mesenchymal stem cell resistance to oxidative stress

Properties of induced pluripotent stem cells (iPSC) have been extensively studied since their first derivation in 2006. However, the modification in reactive oxygen species (ROS) production and detoxification caused by reprogramming still needs to be further elucidated. The objective of this study was to compare the response of iPSC generated from menstrual blood–derived mesenchymal stem cells (mb‐iPSC), embryonic stem cells (H9) and adult menstrual blood–derived mesenchymal stem cells (mbMSC) to ROS exposure and investigate the effects of reprogramming on cellular oxidative stress (OS). mbMSC were extremely resistant to ROS exposure, however, mb‐iPSC were 10‐fold less resistant to H₂O₂, which was very similar to embryonic stem cell sensitivity. Extracellular production of ROS was also similar in mb‐iPSC and H9 and almost threefold lower than in mbMSC. Furthermore, intracellular amounts of ROS were higher in mb‐iPSC and H9 when compared with mbMSC. As the ability to metabolize ROS is related to antioxidant enzymes, we analysed enzyme activities in these cell types. Catalase and superoxide dismutase activities were reduced in mb‐iPSC and H9 when compared with mbMSC. Finally, cell adhesion under OS conditions was impaired in mb‐iPSC when compared with mbMSC, albeit similar to H9. Thus, reprogramming leads to profound modifications in extracellular ROS production accompanied by loss of the ability to handle OS.     

Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo

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A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation

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Adipose-derived mesenchymal stem cells induced PAX8 promotes ovarian cancer cell growth by stabilizing TAZ protein

Our previous studies have shown that the Adipose-derived mesenchymal stem cells (ADSCs) can regulate metastasis and development of ovarian cancer. However, its specific mechanism has yet to be fully revealed. In this study, an RNA-seq approach was adopted to compare the differences in mRNA levels in ovarian cancer cells being given or not given ADSCs. The mRNA level of paired box 8 (PAX8) changed significantly and was confirmed as an important factor in tumour-inducing effect of ADSCs. In comparison with the ovarian cancer cells cultured in the common growth medium, those cultured in the medium supplemented with ADSCs showed a significant increase of the PAX8 level. Moreover, the cancer cell growth could be restricted, even in the ADSC-treated group (P < .05), by inhibiting PAX8. In addition, an overexpression of PAX8 could elevate the proliferation of ovarian cancer cells. Moreover, Co-IP assays in ovarian cancer cells revealed that an interaction existed between endogenous PAX8 and TAZ. And the PAX8 levels regulated the degradation of TAZ. The bioluminescence images captured in vivo manifested that the proliferation and the PAX8 expression level in ovarian cancers increased in the ADMSC-treated group, and the effect of ADSCs in promoting tumours was weakened through inhibiting PAX8. Our findings indicate that the PAX8 expression increment could contribute a role in promoting the ADSC-induced ovarian cancer cell proliferation through TAZ stability regulation.