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Effects of living and metabolically inactive mesenchymal stromal cells and their derivatives on monocytes and macrophages

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World Journal of Stem Cells 2021年第9期13卷 1160-1176页

作者： Alexia Nedel Sant'Ana Anelise Bergmann Araújo fabiany da costa gonçalves Ana Helena Paz Laboratório de Células Tecidos e Genes Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903RSBrazil Centro de Processamento Celular Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903RSBrazil Department of Internal Medicine Erasmus Medical CenterRotterdam 3015 GDNetherlands Departamento de Ciências Morfológicas Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto Alegre 90035-903RSBrazil

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cellsthat have great potential as cell therapy for autoimmune and inflammatorydisorders, as well as for other clinical conditions, due to their immunoregulatoryand regenerative properties. MSCs modulate the inflammatory milieu by releasingsoluble factors and acting through cell-to-cell mechanisms. MSCs switch theclassical inflammatory status of monocytes and macrophages towards a nonclassicaland anti-inflammatory phenotype. This is characterized by an increasedsecretion of anti-inflammatory cytokines, a decreased release of pro-inflammatorycytokines, and changes in the expression of cell membrane molecules and inmetabolic pathways. The MSC modulation of monocyte and macrophage phenotypesseems to be critical for therapy effectiveness in several disease models, sincewhen these cells are depleted, no immunoregulatory effects are observed. Here,we review the effects of living MSCs (metabolically active cells) and metabolicallyinactive MSCs (dead cells that lost metabolic activity by induced inactivation) andtheir derivatives (extracellular vesicles, soluble factors, extracts, and microparticles)on the profile of macrophages and monocytes and the implications forimmunoregulatory and reparative processes. This review includes mechanisms ofaction exhibited in these different therapeutic appro-aches, which induce the antiinflammatoryproperties of monocytes and macrophages. Finally, we overviewseveral possibilities of therapeutic applications of these cells and their derivatives,with results regarding monocytes and macrophages in animal model studies andsome clinical trials.

关键词： Mesenchymal stromal cells Macrophage Monocyte Immunomodulation Cell therapy Immunoregulation

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Dynamic culture improves MSC adhesion on freeze-dried bone as a scaffold for bone engineering

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World Journal of Stem Cells 2012年第2期4卷 9-16页

作者： fabiany da costa gonalves Ana Helena da Rosa Paz Priscila Schmidt Lora Eduardo Pandolfi Passos Elizabeth Obino Cirne-Lima Embryology and Cell Differentiation Laboratory Hospital de Clínicas de Porto AlegreRua Ramiro Barcelos 2350Porto AlegreRS90035-903Brazil

AIM: To investigate the interaction between mesenchymal stem cells (MSCs) and bone grafts using two different cultivation methods: static and dynamic. METHODS: MSCs were isolated from rat bone marrow. MSC culture was analyzed according to the morphology, cell differentiation potential, and surface molecular markers. Before cell culture, freeze-dried bone (FDB) was maintained in culture for 3 d in order to verify culture medium pH. MSCs were co-cultured with FDB using two different cultivation methods: static co-culture (two-dimensional) and dynamic co-culture (three-dimensional). After 24 h of cultivation by dynamic or static methods, histological analysis of Cell adhesion on FDB was performed. Cell viability was assessed by the Trypan Blue exclusion method on days 0, 3 and 6 after dynamic or static culture. Adherent cells were detached from FDB surface, stained with Trypan Blue, and quantified to determine whether the cells remained on the graft surface in prolonged non-dynamic culture. Statistical analyses were performed with SPSS and a P 0.05). In histological analysis, there was a significant difference in the amount of adhered cells on FDB between the two cultivation methods (P day 0, the cell viability in the dynamic system was significantly higher than in the static system (P days 0, 3 and 6 after dynamic culture (P day 6

关键词： Mesenchymal stem cell Cell culture Cell adhesion Bone matrix Freeze drying

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Cell membrane and bioactive factors derived from mesenchymal stromal cells: Cell-free based therapy for inflammatory bowel diseases

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World Journal of Stem Cells 2019年第9期11卷 618-633页

作者： fabiany da costa goncalves Ana Helena Paz Nephrology and Transplantation Internal MedicineErasmus Medical CenterRotterdamGD 3015Netherlands Experimental Research Center Hospital de Clínicas de Porto AlegrePorto AlegreRS 90035-903Brazil

Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s *** the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal ***,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of *** this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory *** so,literature is conflicted regarding the location and persistence of MSC in the body after *** this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic ***,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent *** together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.

关键词： Bioactive factors Cell membrane Mesenchymal stem cells Cell-free therapy Inflammatory bowel diseases

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Intravenous vs intraperitoneal mesenchymal stem cells administration:What is the best route for treating experimental colitis?

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World Journal of Gastroenterology 2014年第48期20卷 18228-18239页

作者： fabiany da costa goncalves Natália Schneider Fernanda Otesbelgue Pinto Fabíola Schons Meyer Fernanda Visioli Bianca Pfaffenseller Patrícia Luciana da costa Lopez Eduardo Pandolfi Passos Elizabeth Obino Cirne-Lima Luíse Meurer Ana Helena Paz Centro de Pesquisa Experimental do Hospital de Clínicas de Porto Alegre Porto Alegre 90035-903Rio Grande do SulBrazil Programa de Pós-Gradua??o:Ciências em Gastroenterologia e Hepatologia Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Faculdade de Odontologia Universidade Federado Rio Grande do SulPorto Alegre 90035-003Rio Grande doSulBrazil

AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of ***:MSCs were isolated from C57BL/6 mouse adipose *** cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular *** acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(DSS)in drinking water ad libitum from days 0 to *** mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and *** disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and *** compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological *** responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 *** rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UDPbiotin nick end labeling ***:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(P<0.001)in reducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and *** histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory *** therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in a

关键词： Ulcerative colitis Dextran sulfate sodium Inflammatory bowel disease Mesenchymal stem cell Cell transplantation Intravenous injection Immunomodulation

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