scholarly journals O24‐1: Regulation of SMAD7 and SOCS1 through metabolic and epigenetics coordination by mesenchymal stem cell‐derived humoral factor STC1 induces anti‐fibrotic and anti‐inflammatory effects in lung injuries

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 62-63
2021 ◽  
Vol 20 (2) ◽  
pp. 426-430
Author(s):  
Nurhasan Agung Prabowo ◽  
Zainal Arifin Adnan ◽  
Arief Nurudhin ◽  
Yulyani Werdiningsih ◽  
Kukuh Prasetyo

Background: Systemic lupus erythematosus is a chronic autoimmune disease that affects target organs. mesenchymal stem cell conditioned medium has immunosuppressive, anti-inflammatory, and immunoregulatory properties in lupus. Methyl prednisolone is a standard drug for lupus with immunosuppressive and anti-inflammatory properties. This study aims to compare the therapeutic effect of mesenchymal stem cell conditioned medium administration compared to methyl prednisolone on interleukin 10 levels and the degree of pulmonary vasculitis of lupus mice. Methods: The subjects were 24 female mice of Mus musculus Balb/C strain, which were categorized into 4 groups of 8 mice, i.e. the control group receiving 0.5 cc of 0.9% NaCl injection and placebo, the lupus group receiving 0.5 cc of pristane injection and placebo, and the treatment mesenchymal stem cell conditioned medium group receiving 0.5 cc pristane injection and mesenchymal stem cell conditioned medium 0,5 cc, and methylprednisolone group receiving 0,5 cc pristiane injection and methylprednisolone p.o 1,5 mg/kgbodyweight. After 24 days the mice were terminated and kidney and blood samples were taken. Statistical analysis was performed using ANOVA test followed by independent T-test. The p value was considered significant when the p < 0.05. Results: The study showed that there was no difference on the levels of interleukin level10 among mesenchymal stem cell conditioned medium goup and methyl prednisolone group (CM = 5,94 ± 2,49 pg/mL, mp = 5,86+1,73 pg/mL; p = 1) and the degree of pulmonary vasculitis (CM= 1,94 ± 0,25, MP=1,89+ 0,11 pg/ml; p = 0.667). Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice. Conclusion: Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice Bangladesh Journal of Medical Science Vol.20(2) 2021 p.426-430


Stem Cells ◽  
2017 ◽  
Vol 35 (6) ◽  
pp. 1493-1504 ◽  
Author(s):  
Kaitlin C. Murphy ◽  
Jacklyn Whitehead ◽  
Patrick C. Falahee ◽  
Dejie Zhou ◽  
Scott I. Simon ◽  
...  

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 956
Author(s):  
Andrianto Andrianto ◽  
Desak Ketut Sekar Cempaka Putri ◽  
Makhyan Jibril Al Farabi ◽  
Teuku Yusrizal ◽  
Hanestya Oky Hermawan

Objective: To evaluate mesenchymal stem cell (MSC) administration safety and efficacy in COVID-19 patients. Methods: We conducted a literature search on PubMed/MEDLINE, medRxiv, EBSCOhost/CINAHL, ProQuest, and Scopus with keywords adjusted to each search engine’s specifications on February 12, 2021. Interventional studies that reviewed MSC efficacy (mortality, hospitalization duration, need for mechanical ventilators, and inflammation markers) and/or safety (adverse events) in COVID-19 patients who were 18 years old or more were included in this study. Study eligibility, data extraction, and study quality assessment were conducted independently by each author. Results: A total of five studies of moderate to high quality with a total of 193 patients were included. One of the three randomized studies included did not apply blinding to either participants or medical professionals. Pooled OR (Odd Ratio) for mortality risk, adverse events incidence, and use of mechanical ventilators for patients on MSC therapy were 0.13 [95% CI: 0.02, 0.68], 0.91 [95% CI: 0.45, 1.86], and 0.42 [95% CI: 0.12, 1.47], respectively. Pooled mean difference for hospitalization duration in the MSC group versus the control was -3.54 [CI 95%: -4.68, -2.40] with 7% heterogeneity. All studies agreed that there was an increase of pro-inflammatory cytokines and a decrease of anti-inflammatory markers that were statistically different in the MSC group. Conclusion: Mesenchymal stem cell administration to COVID-19 patients is safe and effective in reducing mortality and hospitalization duration. Furthermore, a decrease of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines were observed.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ning Zhang ◽  
Chi-Wen Lo ◽  
Takeshi Utsunomiya ◽  
Masahiro Maruyama ◽  
Ejun Huang ◽  
...  

Abstract Background Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect. Methods In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis. Results PDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone. Conclusions Overexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 577
Author(s):  
Marina Gomzikova ◽  
Sevindzh Kletukhina ◽  
Sirina Kurbangaleeva ◽  
Olga Neustroeva ◽  
Olga Vasileva ◽  
...  

Immune-mediated diseases are characterized by abnormal activity of the immune system. The cytochalasin B-induced membrane vesicles (CIMVs) are innovative therapeutic instruments. However, the immunomodulating activity of human mesenchymal stem cell (MSC)-derived CIMVs (CIMVs-MSCs) remains unknown. Therefore, we sought to investigate the immunological properties of CIMVs-MSCs and evaluate their effect on human peripheral blood mononuclear cells (PBMCs). We found that CIMVs-MSCs are primarily uptaken by monocytes and B-cells. Additionally, we demonstrated that CIMVs-MSCs inhibit phytohemagglutinin (PHA)-induced proliferation of PBMCs, with more pronounced effect on T-lymphocytes expansion as compared to that of B-cells. In addition, activation of T-helpers (CD4+CD25+), B-cells (CD19+CD25+), and T-cytotoxic lymphocytes (CD8+CD25+) was also significantly suppressed by CIMVs-MSCs. Additionally, CIMVs-MSCs decreased secretion of epidermal growth factor (EGF) and pro-inflammatory Fractalkine in a population of PBMCs, while the releases of FGF-2, G-CSF, anti-inflammatory GM-CSF, MCP-3, anti-inflammatory MDC, anti-inflammatory IL-12p70, pro-inflammatory IL-1b, and MCP-1 were increased. We analyzed the effect of CIMVs-MSCs on an isolated population of CD4+ and CD8+ T-lymphocytes and demonstrated their different immune response and cytokine secretion. Finally, we observed that no xenogeneic nor allogeneic transplantation of CIMVs induced an immune response in mice. Our data suggest that CIMVs-MSCs have immunosuppressive properties, are potential agents for immunomodulating treatment, and are worthy of further investigation.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Fernando Ezquer ◽  
Paola Morales ◽  
María Elena Quintanilla ◽  
Daniela Santapau ◽  
Carolyne Lespay-Rebolledo ◽  
...  

Author(s):  
Mario Simental‑Mend�a ◽  
Sonia Lozano‑Sep�lveda ◽  
Vanessa P�rez‑Silos ◽  
Lizeth Fuentes‑Mera ◽  
Herminia Mart�nez‑Rodr�guez ◽  
...  

Author(s):  
Jinli Wang ◽  
Emily Bonacquisti ◽  
J. Nguyen

AbstractA limitation to using exosomes to their fullest potential is their limited secretion from cells, a major bottleneck to efficient exosome production and application. This is especially true for mesenchymal stem cell (MSCs), which can self-renew but have limited expansion capacity, undergoing senescence after only a few passages, with exosomes derived from senescent stem cells showing impaired regenerative capacity compared to young cells. Here we examined the effects of small molecule modulators capable of enhancing exosome secretion from MSCs. Treatment of MSCs with a combination of methyldopamine and norepinephrine robustly increased exosome production by three-fold without altering the ability of the MSC exosomes to induce angiogenesis, polarize macrophages to the anti-inflammatory phenotype, or inhibit fibrosis. These small molecule modulators provide a promising means to increase exosome production by MSCs.


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