scholarly journals Adipose-derived Mesenchymal Stromal Cells Modulate Lipid Metabolism and Lipid Droplet Biogenesis via AKT/mTOR –PPARγ Signalling in Macrophages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luciana Souza-Moreira ◽  
Vinicius Cardoso Soares ◽  
Suelen da Silva Gomes Dias ◽  
Patricia T. Bozza
Keyword(s):  
Conditioned Medium ◽  
Lipid Droplet ◽  
Mesenchymal Stromal Cells ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Mtor Inhibitor ◽  
Inflammatory Diseases ◽  
Experimental Colitis ◽  
Arginase 1

AbstractMesenchymal stromal cells (MSCs) are a potential therapy for many chronic inflammatory diseases due to their regenerative, immunologic and anti-inflammatory properties. The two-way dialogue between MSCs and macrophages is crucial to tissue regeneration and repair. Previous research demonstrated that murine adipose-derived MSC conditioned medium (ASCcm) reprograms macrophages to an M2-like phenotype which protects from experimental colitis and sepsis. Here, our focus was to determine the molecular mechanism of lipid droplet biogenesis in macrophages re-educated using ASCcm. Adipose-derived MSC conditioned medium promotes phosphorylation of AKT/mTOR pathway proteins in macrophages. Furthermore, increased expression of PPARγ, lipid droplet biogenesis and PGE2 synthesis were observed in M2-like phenotype macrophages (high expression of arginase 1 and elevated IL-10). Treatment with mTOR inhibitor rapamycin or PPARγ inhibitor GW9662 suppressed lipid droplets and PGE2 secretion. However, these inhibitors had no effect on arginase-1 expression. Rapamycin, but not GW9662, inhibit IL-10 secretion. In conclusion, we demonstrate major effects of ASCcm to reprogram macrophage immunometabolism through mTOR and PPARγ dependent and independent pathways.

Comparison of the Therapeutic Potential of Rat and Human Mesenchymal Stromal Cells and Their Conditioned Media in Local Radiation Lesions

2021 ◽  
Vol 66 (4) ◽  
pp. 5-12
Author(s):  
A. Rastorgueva ◽  
T. Astrelina ◽  
V. Brunchukov ◽  
D. Usupzhanova ◽  
I. Kobzeva ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
White Male ◽  
Conditioned Media ◽  
Control Group ◽  
Skin Ulcers ◽  
Calculated Dose ◽  
Local Radiation ◽  
Gingival Mucosa

Background: To compare the results of the use of mesenchymal stromal cells (MSCs) of human gingival mucosa and MSCs of rat gingival mucosa, their conditioned media, and to evaluate their effect on tissue regeneration in local radiation injury (LRI). Material and methods: The study included 120 white male Wistar rats weighing 210 ± 30 g at the age of 8–12 weeks, randomized into 6 groups (20 animals each): control (C), animals did not receive therapy; control with the introduction of culture medium concentrate (CM) three times for 1, 14, 21 days; administration of human gingival mucosa MSCs (HM) at a dose of 2 million per 1 kg three times for 1, 14, 21 days; administration of human gingival mucosa MSCS conditioned medium concentrate (HMCM) at a calculated dose of 2 million cells per 1 kg three times for 1, 14, 21 days; administration of rat gingival mucosal MSCs (RM) at a dose of 2 million cells per 1 kg three times for 1, 14, 21 days; administration of rat gingival mucosal MSCS (RMCM) conditioned medium concentrate at a calculated dose of 2 million cells per 1 kg three times for 1, 14, 21 days. Each laboratory animal was observed 17 times: on 1, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, 98, 105, 112 day after the burn simulation. Histological (hematoxylin-eosin staining) and immunohistochemical (CD31, CD68, VEGF, PGP 9.5, MMP2,9, Collag 1, TIMP 2) studies were performed. LRI was modeled on an X-ray machine at a dose of 110 Gy. MSCs were cultured according to the standard method up to 3–5 passages, the conditioned medium was taken and concentrated 10 times. The immunophenotype of MSCs (CD34, CD45, CD90, CD105, CD73, HLA-DR) and viability (7‑ADD) were determined by flow cytofluorimetry. Results: In a comparative analysis with the control group (C), starting from the 42nd day of the study, a tendency to reduce the area of skin ulcers in animals in all groups was observed, despite the fact that not all days had statistically significant differences. On day 112th, complete healing of skin ulcers in the CM group was observed in 40 % of animals in the HM group – in 60 %, in the HMCM group – in 20 % of animals, in the RMCM group–20 %, and in the C and RM groups there were no animals with a prolonged wound defect. Positive expression of the VEGF marker was observed in groups C and CM on the 28th day and in experimental groups (HM, HMCM, RM, RMCM) on the 112th day. A statistically significant increase in the CD68 marker was observed in groups C, RM, and RMCM, while the remaining groups showed a decrease in the number of macrophages.

scholarly journals Mesenchymal Stromal Cells Derived Conditioned Medium in Pulmonary Fibrosis: A Systematic Review and Meta-analysis

2020 ◽  
Vol 23 (12) ◽  
pp. 870-879
Author(s):  
Kosar Mohamed Ali ◽  
Fattah Hama Rahim Fattah ◽  
Shirwan Hamasalh Omar ◽  
Mohammed I M Gubari ◽  
Mahmoud Yousefifard ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interleukin 6 ◽  
Meta Analysis ◽  
Type Iii Collagen ◽  
Type I ◽  
Collagen Deposition ◽  
Tgf Β1

Background: A definitive conclusion on the efficacy of mesenchymal stromal cells-derived conditioned medium (MSCs-CM) in pulmonary fibrosis has not yet been reached. Therefore, the present meta-analysis intends to investigate the efficacy of MSCs-CM administration on improvement of pulmonary fibrosis. Methods: An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of August 2019. Outcomes in the present study included pulmonary fibrosis score, lung collagen deposition, lung collagen expression, transforming growth factor β1 (TGF-β1) expression and interleukin-6 expression. Finally, the data were pooled and an overall standardized mean difference (SMD) with a 95% confidence interval (CI) was reported. Results: Data from seven studies were included. Analyses showed that administration of MSCs-CM significantly improved pulmonary fibrosis (SMD = -2.36; 95% CI: -3.21, -1.51). MSCs-CM administration also attenuated lung collagen deposition (SMD = -1.70; 95% CI: -2.18, -1.23) and decreased expression of type I collagen (SMD = -6.27; 95% CI: -11.00, -1.55), type III collagen (SMD = -5.16; 95% CI: -9.86, -0.47), TGF- β1 (SMD = -3.36; 95% CI: - 5.62, -1.09) and interleukin-6 (SMD = -1.69; 95% CI: - 3.14, -0.24). Conclusion: The present meta-analysis showed that administration of MSCs-CM improves pulmonary fibrosis. It seems that the effect of MSCs-CM was mediated by reducing collagen deposition as well as inhibiting the production of inflammatory chemokines such as TGF-β1 and interleukin 6 (IL-6). Since there is no evidence on the efficacy of MSCs-CM in large animals, further studies are needed to translate the finding to clinical studies.

Endoscopic Bowel Injections of Mesenchymal Stromal Cells Alleviate Experimental Colitis

2017 ◽  
Vol 152 (5) ◽  
pp. S30
Author(s):  
Marieke C. Barnhoorn ◽  
Eveline de Jonge-Muller ◽  
Marij Mieremet-Ooms ◽  
Danny van der Helm ◽  
Mandy van Gulijk ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Experimental Colitis

scholarly journals Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Maria Tolomeo ◽  
Ignazio Castagliuolo ◽  
Martina Piccoli ◽  
Michele Grassi ◽  
Fabio Magarotto ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Dextran Sulfate ◽  
Experimental Colitis ◽  
Culture Conditions ◽  
Experimental Conditions ◽  
Intestinal Fibrosis ◽  
Cells Of Origin

Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.

scholarly journals Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells

2020 ◽  
Vol 17 (167) ◽  
pp. 20190815
Author(s):  
Devlin T. Boyt ◽  
Lauren K. Boland ◽  
Anthony J. Burand ◽  
Alex J. Brown ◽  
James A. Ankrum
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Interferon Γ ◽  
Relative Role ◽  
Peripheral Blood Mononuclear ◽  
High Performing ◽  
Indoleamine 2,3 Dioxygenase

Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for in vivo exposure to cytokines, MSCs can be pre-licensed during manufacturing to enhance IDO expression. In this study, we systematically examine the relative role that the dose of IFNγ, the duration of pre-licensing and the donor of origin play in dictating MSC production of functional IDO. We find that across three human MSC donors, MSCs increase their expression of IDO in response to both increased dose of IFNγ and duration of pre-licensing. However, with extended pre-licensing, the expression of IDO no longer predicts MSCs ability to suppress activated peripheral blood mononuclear cells. In addition, pre-licensing dose and duration are revealed to be minor modifiers of MSCs inherent potency, and thus cannot be manipulated to boost poor donors to the levels of high-performing donors. Thus, the dose and duration of pre-licensing should be tailored to optimize performance of specific donors and an emphasis on donor selection is needed to realize significant benefits of pre-licensing.

scholarly journals NVP-BEZ235, a dual pan class I PI3 kinase and mTOR inhibitor, promotes osteogenic differentiation in human mesenchymal stromal cells

2010 ◽  
Vol 25 (10) ◽  
pp. 2126-2137 ◽  
Author(s):  
Sally K Martin ◽  
Stephen Fitter ◽  
Li Fei Bong ◽  
Jennifer J Drew ◽  
Stan Gronthos ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mtor Inhibitor ◽  
Pi3 Kinase ◽  
Class I ◽  
Human Mesenchymal Stromal Cells
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