Bone Marrow‐Derived Mesenchymal Stem Cells‐Mediated Protection Against Organ Dysfunction in Disseminated Intravascular Coagulation Is Associated With Peripheral Immune Responses

Tang²,

et al. 2019

OTT

These authors contributed equally to this work Purpose: Sodium selenite (Na 2 SeO 3 ) has been known to restore the antioxidant capacity of bone marrow mesenchymal stem cells (BMSCs), reduce the production of reactive oxygen species (ROS) in the cells, and promote cell proliferation and inhibit cell apoptosis. However, it is still not clear whether selenium can mediate the differentiation and inhibit the induced hemagglutination of BMSCs. In this study, we attempted to explore the effect of Na 2 SeO 3 on these aspects of BMSCs. Methods: We evaluated the fate of the MSCs isolated from the bone marrow of mice by studying their differentiation and proliferation after treatment with Na 2 SeO 3 . We also simultaneously evaluated the coagulation reaction induced by Na 2 SeO 3-treated BMSCs in vitro. Results: While the mice-derived BMSCs expressed CD44, CD73, CD90, and CD105, they did not express CD45. The morphology of the derived cells was homogeneously elongated. These results showed that the isolated cells are indeed BMSCs. We found that 0.1 μM and 1 μM of Na 2 SeO 3 promoted the proliferation and apoptosis of BMSCs, respectively. This showed that Na 2 SeO 3 can be toxic and exert certain side effects on the BMSCs. The results of the osteogenic and adipogenic assay showed that 0.1 μM Na 2 SeO 3 could significantly promote the osteogenic and adipogenic differentiation of BMSCs by upregulating the lipid factors (LPL and PPRAG) and osteogenic factors, RUNX2, COL1, and BGP, in a concentration-dependent manner. Coagulation experiments in animals (mice and rats) revealed that Na 2 SeO 3 can reduce the coagulation time of BMSCs in a concentration-dependent manner, which is related to the high expression of hematopoietic factors (SDF-1α, GM-CSF, IL-7, IL-8, IL-11, and SCF). Conclusion: Na 2 SeO 3 promotes the proliferation and differentiation as well as reduces the coagulation time of BMSCs, and this effect might enhance the therapeutic effect of BMSCs.

Section: Discussionmentioning

confidence: 99%

<p>Sodium Selenite Improves The Therapeutic Effect Of BMSCs Via Promoting The Proliferation And Differentiation, Thereby Promoting The Hematopoietic Factors</p>

Tang²,

et al. 2019

OTT

“…The establishment DIC rat model was performed according to the methods described by our previous studies 23 , 26 . Rats were anesthetized with an intraperitoneal injection of pentobarbital sodium salt (30 mg/kg, Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model

Wang

et al. 2018

Cell Death Dis

Self Cite

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on disseminated intravascular coagulation (DIC) model rats and to further explore the underlying mechanism. A rat model of lipopolysaccharide (LPS)-induced DIC was successfully established, as indicated by impaired plasma hemostatic parameters and damaged organ functions in rats. Importantly, pre-treatment with rat allogeneic BMSCs before LPS injection significantly alleviated systemic intravascular coagulation, reduced plasma levels of organ dysfunction indicators and pro-inflammatory cytokines, suppressed fibrin microthrombi formation, ameliorated liver, heart, and renal injuries, and increased 24-hour survival rates in LPS-induced DIC rats. The protection of BMSCs against DIC was in a moderately dose-dependent manner. Further investigation revealed that BMSCs co-cultured with peripheral blood mononuclear cells (PBMCs) significantly inhibited the LPS-stimulated PBMCs proliferation and the release of pro-inflammatory cytokines from PBMCs. Of note, upregulation of immunosuppressive factors including indoleamine 2,3-dioxygenase and interleukin-10, which was induced by interferon-γ, contributed to BMSCs-mediated inhibition of LPS-stimulated PBMCs proliferation. These effects do not depend on the direct cell–cell contact. In conclusion, BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced DIC model rats. The protection of BMSCs may be attributed to their anti-inflammatory and immunomodulatory properties, which render BMSCs a promising source for stem cell-based therapeutic approaches in inflammation-related DIC.

“…Mesenchymal stem cells (MSCs) can undergo self-renewal and differentiation into various cell types and tissues including chondrocytes, osteoblasts, and adipocytes [ 12 ]. Many studies have demonstrated that MSCs can suppress the activation and function of innate and adaptive immune cells, including macrophages [ 13 ], neutrophils [ 14 ], natural killer cells [ 15 ], dendritic cells [ 16 ], and T cells [ 17 ]. Many preclinical studies have demonstrated that treatment with MSCs can improve survival, reduce inflammation, and enhance bacterial clearance [ 18 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury

Feng

Zhu

et al. 2020

Stem Cell Res Ther

Background Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment. Methods We investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7. Results MSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling. Conclusions Lung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.