Journal ArticleDOI
Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis
Per Anderson,Luciana Souza-Moreira,Maria Morell,Marta Caro,Francisco O'Valle,Elena Gonzalez-Rey,Mario Delgado +6 more
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TLDR
ASCs induce a distinct regulatory activation state of macrophages which possess potent immunomodulatory ability and therapeutic potential in inflammatory bowel diseases and sepsis.Abstract:
Objective To investigate the effect of adipose-derived mesenchymal stromal cells (ASCs) on the activation state of macrophages (MΦ) in vitro, and the potential therapeutic effect of these cells in experimental colitis and sepsis. Design Murine bone marrow-derived macrophages were cultured with ASCs or with ASC conditioned media (ASC-MΦ) and characterised for the expression of several regulatory macrophage markers, including enzymes and cytokines, and for their immunomodulatory capacity in vitro. The therapeutic effect was investigated of ASC-MΦ in two models of experimental inflammatory colitis induced by trinitrobenzene sulphonic acid and dextran sodium sulphate, and in polymicrobial sepsis induced by caecal ligation and puncture. Results ASC-MΦ showed a phenotype that clearly differed from the classically activated macrophages or the alternatively activated macrophages induced by interleukin (IL)-4, characterised by high arginase activity, increased production of IL-10 upon restimulation and potent immunosuppressive activity on T cells and macrophages. Activation of cyclo-oxygenase-2 on ASCs seems to be critically involved in inducing this phenotype. Systemic infusion of ASC-MΦ inhibited colitis in mice, reducing mortality and weight loss while lowering the colonic and systemic levels of inflammatory cytokines. Importantly, therapeutic injection of ASC-MΦ in established chronic colitis alleviated its progression and avoided disease recurrence. Moreover, ASC-MΦ protected from severe sepsis by reducing the infiltration of inflammatory cells into various organs and by downregulating the production of several inflammatory mediators, where ASC-MΦ-derived IL-10 played a critical role. Conclusion ASCs induce a distinct regulatory activation state of macrophages which possess potent immunomodulatory ability and therapeutic potential in inflammatory bowel diseases and sepsis.read more
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Exosomal miR‐146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin‐1β‐Primed Mesenchymal Stem Cells Against Sepsis
Yuxian Song,Dou Huan,Xiujun Li,Zhao Xiaoyin,Yi Li,Dan Liu,Jianjian Ji,Fei Liu,Liang Ding,Ni Yanhong,Yayi Hou +10 more
TL;DR: It is found that systemic administration of IL‐1β‐pretreated MSCs (βMSCs) is found to be ameliorated the symptoms of murine sepsis more effectively and increased the survival rate compared with naïve M SCs, and it is believed that IL‐ 1β pretreatment may provide a new modality for better therapeutic application of MSCS in inflammatory disorders.
Journal ArticleDOI
Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis.
Xiaohong Wang,Haitao Gu,Dongze Qin,Dongze Qin,Liwang Yang,Liwang Yang,Wei Huang,Kobina Essandoh,Yigang Wang,Charles C. Caldwell,Tianqing Peng,Basilia Zingarelli,Guo-Chang Fan +12 more
TL;DR: Exosomal miR-223 plays an essential role for MSC-induced cardio-protection in sepsis, and is identified as a target for down-regulation of Sema3A and Stat3 in WT-exosomes.
Journal ArticleDOI
Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases
TL;DR: Mesenchymal stem cells (MSCs) represent a heterogenous population of adult, fibroblast-like multi-potent cells, and they can migrate to the sites of inflammation and hold potent of immunomodulatory and anti-inflammatory effects through cell and cell interactions between MSCs and lymphocytes as mentioned in this paper.
Journal ArticleDOI
Mesenchymal Stem Cells Reduce Colitis in Mice via Release of TSG6, Independently of Their Localization to the Intestine.
Emanuela Sala,Marco Genua,Luciana Petti,Achille Anselmo,V. Arena,Javier Cibella,Lucia Zanotti,Silvia D'Alessio,Franco Scaldaferri,Giovanni Luca,Iva Arato,Riccardo Calafiore,Alessandro Sgambato,Sergio Rutella,Massimo Locati,Silvio Danese,Stefania Vetrano +16 more
TL;DR: BM-MSCs injected into mice with colitis do not localize to the intestine but instead form aggregates in the peritoneum where they produce immunoregulatory molecules, including TSG6, that reduce intestinal inflammation.
Journal ArticleDOI
Cell Senescence Abrogates the Therapeutic Potential of Human Mesenchymal Stem Cells in the Lethal Endotoxemia Model
Juan Carlos Sepúlveda,María Tomé,María Eugenia Fernández,Mario Delgado,Judith Campisi,Antonio Bernad,Antonio Bernad,Manuel A. González +7 more
TL;DR: It is shown that senescence induces extensive phenotypic changes in hMSCs and abrogates their protective activity in a murine model of LPS‐induced lethal endotoxemia and provides candidate gene signatures which may be useful to evaluate the therapeutic potential of h MSCs used in future clinical studies.
References
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Exploring the full spectrum of macrophage activation.
TL;DR: This Review suggests a new grouping of macrophages based on three different homeostatic activities — host defence, wound healing and immune regulation, and proposes that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation.
Journal ArticleDOI
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
Antoine E. Karnoub,Ajeeta B. Dash,Annie P. Vo,Andrew J. Sullivan,Mary W. Brooks,George W. Bell,Andrea L. Richardson,Kornelia Polyak,Ross Tubo,Robert A. Weinberg +9 more
TL;DR: It is demonstrated that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft.
Journal ArticleDOI
Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production.
Krisztián Németh,Asada Leelahavanichkul,Peter S.T. Yuen,Balázs Mayer,Alissa Parmelee,Kent Doi,Pamela Gehron Robey,Kantima Leelahavanichkul,Beverly H. Koller,Jared M. Brown,Xuzhen Hu,Ivett Jelinek,Robert A. Star,Eva Mezey +13 more
TL;DR: It is suggested that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups because they have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching.
Journal ArticleDOI
Arginase I Production in the Tumor Microenvironment by Mature Myeloid Cells Inhibits T-Cell Receptor Expression and Antigen-Specific T-Cell Responses
Paulo C. Rodriguez,David G. Quiceno,Jovanny Zabaleta,Blair Ortiz,Arnold H. Zea,Maria Blanca Piazuelo,Alberto G. Delgado,Pelayo Correa,Jason Brayer,Eduardo M. Sotomayor,Scott J. Antonia,Juan B. Ochoa,Augusto C. Ochoa +12 more
TL;DR: High levels of arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies.
Journal ArticleDOI
Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity
Lesley E. Smythies,Marty T. Sellers,Ronald H. Clements,Meg Mosteller-Barnum,Gang Meng,William H. Benjamin,Jan M. Orenstein,Phillip D. Smith +7 more
TL;DR: It is shown that intestinal stromal cell-derived products downregulate both monocyte receptor expression and, via TGF-beta, cytokine production but not phagocytic or bacteriocidal activity, eliciting the phenotype and functional profile of intestinal macrophages.