Extracellular membrane vesicles from umbilical cord blood-derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning

References

• Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol. 1967; 13: 269–88.
   PubMed Web of Science ®Google Scholar
• Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia. 2006; 20: 1487–95.
   PubMed Web of Science ®Google Scholar
• György B, Módos K, Pállinger É, Pálóczi K, Pásztói M, Misják P, etal. Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters. Blood. 2011; 117: e39–48.
   PubMed Web of Science ®Google Scholar
• Van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 2012; 64: 676–705.
   PubMed Web of Science ®Google Scholar
• Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9: 654–9.
   PubMed Web of Science ®Google Scholar
• Tomasoni S, Longaretti L, Rota C, Morigi M, Conti S, Gotti E, etal. Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells. Stem Cells Dev. 2013; 22: 772–80.
   PubMed Web of Science ®Google Scholar
• Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009; 9: 581–93.
   PubMed Web of Science ®Google Scholar
• Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, etal. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008; 371: 1579–86.
   PubMed Web of Science ®Google Scholar
• Dalal J, Gandy K, Domen J. Role of mesenchymal stem cell therapy in Crohn's disease. Pediatr Res. 2012; 71: 445–51.
   PubMed Web of Science ®Google Scholar
• MacDonald GIA, Augello A, De Bari C. Role of mesenchymal stem cells in reestablishing immunologic tolerance in autoimmune rheumatic diseases. Arthritis Rheum. 2011; 63: 2547–57.
   PubMed Web of Science ®Google Scholar
• Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, etal. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002; 99: 3838–43.
   PubMed Web of Science ®Google Scholar
• English K, Ryan JM, Tobin L, Murphy MJ, Barry FP, Mahon BP. Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4 + CD25Highforkhead box P3+ regulatory T cells. Clin Exp Immunol. 2009; 156: 149–60.
   PubMed Web of Science ®Google Scholar
• Kong QF, Sun B, Wang GY, Zhai DX, Mu LL, Wang DD, etal. BM stromal cells ameliorate experimental autoimmune myasthenia gravis by altering the balance of Th cells through the secretion of IDO. Eur J Immunol. 2009; 39: 800–9.
   PubMed Web of Science ®Google Scholar
• Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005; 105: 1815–22.
   PubMed Web of Science ®Google Scholar
• Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004; 103: 4619–21.
   PubMed Web of Science ®Google Scholar
• He J, Wang Y, Sun S, Yu M, Wang C, Pei X, etal. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology. 2012; 17: 493–500.
   PubMed Web of Science ®Google Scholar
• Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, etal. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant. 2011; 26: 1474–83.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Xu H, Xu W, Wang B, Wu H, Tao Y, etal. Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther. 2013; 4: 34.
   PubMed Web of Science ®Google Scholar
• Togel FE, Westenfelder C. Mesenchymal stem cells: a new therapeutic tool for AKI. Nat Rev Nephrol. 2010; 6: 179–83.
   PubMed Web of Science ®Google Scholar
• Okusa MD. The inflammatory cascade in acute ischemic renal failure. Nephron. 2002; 90: 133–8.
   PubMed Web of Science ®Google Scholar
• Ascon DB, Lopez-Briones S, Liu M, Ascon M, Savransky V, Colvin RB, etal. Phenotypic and functional characterization of kidney-infiltrating lymphocytes in renal ischemia reperfusion injury. J Immunol. 2006; 177: 3380–7.
   Web of Science ®Google Scholar
• Kinsey GR, Huang L, Vergis AL, Li L, Okusa MD. Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney. Kidney Int. 2010; 77: 771–80.
   PubMed Web of Science ®Google Scholar
• Gandolfo MT, Jang HR, Bagnasco SM, Ko GJ, Agreda P, Satpute SR, etal. Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury. Kidney Int. 2009; 76: 717–29.
   Web of Science ®Google Scholar
• Asanuma H, Meldrum DR, Meldrum KK. Therapeutic applications of mesenchymal stem cells to repair kidney injury. J Urol. 2010; 184: 26–33.
   Web of Science ®Google Scholar
• Cantaluppi V, Gatti S, Medica D, Figliolini F, Bruno S, Deregibus MC, etal. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells. Kidney Int. 2012; 82: 412–27.
   PubMed Web of Science ®Google Scholar
• DelaRosa O, Lombardo E, Beraza A, Mancheno-Corvo P, Ramirez C, Menta R, etal. Requirement of IFN-gamma-mediated indoleamine 2,3-dioxygenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng Part A. 2009; 15: 2795–806.
   PubMed Web of Science ®Google Scholar
• Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, etal. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008; 2: 141–50.
   PubMed Web of Science ®Google Scholar
• English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol Lett. 2007; 110: 91–100.
   PubMed Web of Science ®Google Scholar
• Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007; 149: 353–63.
   PubMed Web of Science ®Google Scholar
• Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, etal. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008; 38: 1745–55.
   PubMed Web of Science ®Google Scholar
• Krampera M. Mesenchymal stromal cell ‘licensing’: a multistep process. Leukemia. 2011; 25: 1408–14.
   PubMed Web of Science ®Google Scholar
• Sheng H, Wang Y, Jin Y, Zhang Q, Zhang Y, Wang L, etal. A critical role of IFN-gamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell Res. 2008; 18: 846–57.
   PubMed Web of Science ®Google Scholar
• Bieback K, Kern S, Kocaomer A, Ferlik K, Bugert P. Comparing mesenchymal stromal cells from different human tissues: bone marrow, adipose tissue and umbilical cord blood. Biomed Mater Eng. 2008; 18(1 Suppl): 71–6.
   PubMed Web of Science ®Google Scholar
• Najar M, Raicevic G, Boufker HI, Kazan HF, Bruyn CD, Meuleman N, etal. Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: combined comparison of adipose tissue, Wharton's Jelly and bone marrow sources. Cell Immunol. 2010; 264: 171–9.
   PubMed Web of Science ®Google Scholar
• Hsiao ST, Asgari A, Lokmic Z, Sinclair R, Dusting GJ, Lim SY, etal. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev. 2012; 21: 2189–203.
   PubMed Web of Science ®Google Scholar
• Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, IFNgamma and TNF-alpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One. 2010; 5: e9016.
   PubMed Web of Science ®Google Scholar
• Laitinen A, Nystedt J, Laitinen S. The isolation and culture of human cord blood-derived mesenchymal stem cells under low oxygen conditions. Methods Mol Biol. 2011; 698: 63–73.
   Google Scholar
• Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, etal. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315–7.
   PubMed Web of Science ®Google Scholar
• O'Connell KL, Stults JT. Identification of mouse liver proteins on two-dimensional electrophoresis gels by matrix-assisted laser desorption/ionization mass spectrometry of in situ enzymatic digests. Electrophoresis. 1997; 18: 349–59.
   PubMed Web of Science ®Google Scholar
• Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. 2006; 1: 2856–60.
   PubMed Web of Science ®Google Scholar
• Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4: 44–57.
   PubMed Web of Science ®Google Scholar
• Lempiäinen J, Finckenberg P, Levijoki J, Mervaala E. AMPK activator AICAR ameliorates ischaemia reperfusion injury in the rat kidney. Br J Pharmacol. 2012; 166: 1905–15.
   PubMed Web of Science ®Google Scholar
• Mathivanan S, Fahner CJ, Reid GE, Simpson RJ. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 2012; 40: D1241–4.
   PubMed Web of Science ®Google Scholar
• Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, etal. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells. 2008; 26: 212–22.
   PubMed Web of Science ®Google Scholar
• Ianni MD, Beatrice DP, Ioanni MD, Moretti L, Bonifacio E, Cecchini D, etal. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol. 2008; 36: 309–18.
   PubMed Web of Science ®Google Scholar
• Casiraghi F, Azzollini N, Cassis P, Imberti B, Morigi M, Cugini D, etal. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T-cells. J Immunol. 2008; 181: 3933–46.
   PubMed Web of Science ®Google Scholar
• Engela AU, Hoogduijn MJ, Boer K, Litjens NHR, Betjes MGH, Weimar W, etal. Human adipose-tissue derived mesenchymal stem cells induce functional de novo regulatory T-cells with methylated FOXP3 gene DNA. Clin Exp Immunol. 2013; 173: 343–54.
   PubMed Web of Science ®Google Scholar
• Duffy MM, Pindjakova J, Hanley SA, McCarthy C, Weidhofer GA, Sweeney EM, etal. Mesenchymal stem cell inhibition of T-helper 17 cell-differentiation is triggered by cell–cell contact and mediated by prostaglandin E2 via the EP4 receptor. Eur J Immunol. 2011; 41: 2840–51.
   PubMed Web of Science ®Google Scholar
• Ghannam S, Pène J, Torcy-Moquet G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol. 2010; 185: 302–12.
   PubMed Web of Science ®Google Scholar
• Opitz CA, Litzenburger UM, Lutz C, Lanz TV, Tritschler I, Köppel A, etal. Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-beta and protein Kinase R. Stem Cells. 2009; 27: 909–19.
   PubMed Web of Science ®Google Scholar
• Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, etal. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010; 4: 214–22.
   PubMed Web of Science ®Google Scholar
• Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, etal. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells. 2012; 30: 1556–64.
   PubMed Web of Science ®Google Scholar
• Mokarizadeh A, Delirezh N, Morshedi A, Mosayebi G, Farshid A, Mardani K. Microvesicles derived from mesenchymal stem cells: potent organelles for induction of tolerogenic signaling. Immunol Lett. 2012; 147: 47–54.
   PubMed Web of Science ®Google Scholar
• Wu S, Ju G, Du T, Zhu Y, Liu G. Microvesicles derived from human umbilical cord Wharton's Jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo. PLoS One. 2013; 8: e61366.
   PubMed Web of Science ®Google Scholar
• Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, etal. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol. 2009; 20: 1053–67.
   PubMed Web of Science ®Google Scholar
• Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, etal. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One. 2010; 5: 11803.
   PubMed Web of Science ®Google Scholar
• Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011; 121: 4210–21.
   PubMed Web of Science ®Google Scholar
• Alexandre CS, Volpini RA, Shimizu MH, Sanches TR, Semedo P, di Jura VL, etal. Lineage-negative bone marrow cells protect against chronic renal failure. Stem Cells. 2009; 27: 682–92.
   PubMed Web of Science ®Google Scholar
• Herrera MB, Bussolati B, Bruno S, Morando L, Mauriello-Romanazzi G, Sanavio F, etal. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int. 2007; 72: 430–41.
   PubMed Web of Science ®Google Scholar
• Behr L, Hekmati M, Lucchini A, Houcinet K, Faussat AM, Borenstein N, etal. Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury. Cell Prolif. 2009; 42: 284–97.
   PubMed Web of Science ®Google Scholar
• Perico N, Casiraghi F, Introna M, Gotti E, Todeschini M, Cavinato RA, etal. Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility. Clin J Am Soc Nephrol. 2011; 6: 412–22.
   PubMed Web of Science ®Google Scholar
• Ninichuk V, Gross O, Segerer S, Hoffmann R, Radomska E, Buchstaller A, etal. Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int. 2006; 70: 121–9.
   PubMed Web of Science ®Google Scholar
• Lindoso RS, Araujo DS, Adao-Novaes J, Mariante RM, Verdoorn KS, Fragel-Madeira L, etal. Paracrine interaction between bone marrow-derived stem cells and renal epithelial cells. Cell Physiol Biochem. 2011; 28: 267–78.
   Web of Science ®Google Scholar
• Hu J, Zhang L, Wang N, Ding R, Cui S, Zhu F, etal. Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions. Kidney Int. 2013;84:521–31
   Web of Science ®Google Scholar
• Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012; 12: 383–96.
   PubMed Web of Science ®Google Scholar
• Lepelletier Y, Lecourt S, Renand A, Arnulf B, Vanneaux V, Fermand JP, etal. Galectin-1 and semaphorin-3A are two soluble factors conferring T-cell immunosuppression to bone marrow mesenchymal stem cell. Stem Cells Dev. 2010; 19: 1075–9.
   Web of Science ®Google Scholar
• Gieseke F, Bohringer J, Bussolari R, Dominici M, Handgretinger R, Muller I. Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood. 2010; 116: 3770–9.
   PubMed Web of Science ®Google Scholar
• Sioud M, Mobergslien A, Boudabous A, Floisand Y. Mesenchymal stem cell-mediated T cell suppression occurs through secreted galectins. Int J Oncol. 2011; 38: 385–90.
   PubMed Web of Science ®Google Scholar
• Garín MI, Chu C, Golshayan D, Cernuda-Morollón E, Wait R, Lechler RI. Galectin-1: a key effector of regulation mediated by CD4 + CD25+ T cells. Blood. 2007; 109: 2058–65.
   PubMed Web of Science ®Google Scholar
• Sattler C, Steinsdoerfer M, Offers M, Fischer E, Schierl R, Heseler K, etal. Inhibition of T-cell proliferation by murine multipotent mesenchymal stromal cells is mediated by CD39 expression and adenosine generation. Cell Transplant. 2011; 20: 1221–30.
   Web of Science ®Google Scholar
• Campioni D, Rizzo R, Stignani M, Melchiorri L, Ferrari L, Moretti S, etal. A decreased positivity for CD90 on human mesenchymal stromal cells (MSCs) is associated with a loss of immunosuppressive activity by MSCs. Cytometry B Clin Cytom. 2009; 76: 225–30.
   PubMedGoogle Scholar
• Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, etal. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007; 204: 1257–65.
   PubMed Web of Science ®Google Scholar
• Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, etal. IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest. 2010; 120: 331–42.
   PubMed Web of Science ®Google Scholar
• Tsukamoto H, Chernogorova P, Ayata K, Gerlach UV, Rughani A, Ritchey JW, etal. Deficiency of CD73/ecto-5′-nucleotidase in mice enhances acute graft-versus-host disease. Blood. 2012; 119: 4554–64.
   PubMed Web of Science ®Google Scholar
• Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 2009; 10: 513–25.
   PubMed Web of Science ®Google Scholar
• Pfeffer SR. Two Rabs for exosome release. Nat Cell Biol. 2010; 12: 3–4.
   Web of Science ®Google Scholar
• Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, etal. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010; 12: 19–30. sup pp 1–13.
   PubMed Web of Science ®Google Scholar
• Hutagalung AH, Novick PJ. Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev. 2011; 91: 119–49.
   PubMed Web of Science ®Google Scholar
• Bultema JJ, Di Pietro SM. Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles. Small GTPases. 2013; 4: 16–21.
   PubMedGoogle Scholar
• Wang C, Liu Z, Huang X. Rab32 is important for autophagy and lipid storage in Drosophila. PLoS One. 2012; 7: e32086.
   PubMed Web of Science ®Google Scholar
• Goldenberg NM, Grinstein S, Silverman M. Golgi-bound Rab34 is a novel member of the secretory pathway. Mol Biol Cell. 2007; 18: 4762–71.
   Web of Science ®Google Scholar
• Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, etal. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem. 2003; 278: 10963–72.
   PubMed Web of Science ®Google Scholar
• Kim CH, Wu W, Wysoczynski M, Abdel-Latif A, Sunkara M, Morris A, etal. Conditioning for hematopoietic transplantation activates the complement cascade and induces a proteolytic environment in bone marrow: a novel role for bioactive lipids and soluble C5b-C9 as homing factors. Leukemia. 2012; 26: 106–16.
   Web of Science ®Google Scholar
• Mevorach D, Mascarenhas JO, Gershov D, Elkon KB. Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med. 1998; 188: 2313–20.
   PubMed Web of Science ®Google Scholar
• Gullstrand B, Martensson U, Sturfelt G, Bengtsson AA, Truedsson L. Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells. Clin Exp Immunol. 2009; 156: 303–11.
   Web of Science ®Google Scholar
• Tran-Dinh A, Diallo D, Delbosc S, Varela-Perez LM, Dang Q, Lapergue B, etal. HDL and endothelial protection. Br J Pharmacol. 2013; 169: 493–511.
   PubMed Web of Science ®Google Scholar
• Shi N, Wu MP. Apolipoprotein A-I attenuates renal ischemia/reperfusion injury in rats. J Biomed Sci. 2008; 15: 577–83.
   PubMed Web of Science ®Google Scholar