期刊论文详细信息
Journal of Translational Medicine
A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods
Neil H Riordan2  Kosagisharaf S Rao1  Marialaura Madrigal2 
[1] INDICASAT-AIP, City of Knowledge, Republic of Panama;MediStem Panama Inc., City of Knowledge, Republic of Panama
关键词: Conditioned media;    Cell therapy;    TSG-6;    PGE2;    VEGF;    Spheroids;    Inflammation;    Hypoxia;    MSC;   
Others  :  1147692
DOI  :  10.1186/s12967-014-0260-8
 received in 2014-06-28, accepted in 2014-09-10,  发布年份 2014
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【 摘 要 】

The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture. Finally we review in detail the most important factors present in conditioned medium of MSC that can be considered protagonists of MSC physiological effects including HGF, TGF-b, VEGF, TSG-6, PGE2 and galectins 1, and 9. We conclude that there is potential for the development of acellular therapeutic interventions for autoimmune, inflammatory, and malignant diseases and tissue regeneration from cellular secretions derived from MSCs cultured under the appropriate conditions.

【 授权许可】

   
2014 Madrigal et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997, 276(5309):71-74.
  • [2]Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP: Heterotopic transplants of bone marrow. Transplantation 1968, 6(2):230-247.
  • [3]Zannettino ACW, Paton S, Arthur A, Khor F, Itescu S, Gimble JM, Gronthos S: Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol 2008, 214(2):413-421.
  • [4]Hoogduijn MJ, Crop MJ, Peeters AMA, Van Osch GJV, Balk AHM, Ijzermans JNM, Baan CC: Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev 2007, 16(4):597-604.
  • [5]Chao KC, Chao KF, Fu YS, Liu SH: Islet-like clusters derived from mesenchymal stem cells in Wharton¿s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PloS one 2008, 3(1):e1451.
  • [6]Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, Choung PH: Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng 2007, 13(4):767-773.
  • [7]He Q, Wan C, Li G: Concise review: multipotent mesenchymal stromal cells in blood. Stem cells (Dayton, Ohio) 2007, 25(1):69-77.
  • [8]Oh W, Kim DS, Yang YS, Lee JK: Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cellular Immunol 2008, 251(2):116-123.
  • [9]Meng X, Ichim TE, Zhong J, Rogers A, Yin Z, Jackson J, Riordan NH: Endometrial regenerative cells: a novel stem cell population. J Transl Med 2007, 5:57.
  • [10]Hida N, Nishiyama N, Miyoshi S, Kira S, Segawa K, Uyama T, Umezawa A: Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem cells 2008, 26(7):1695-1704.
  • [11]Patel AN, Park E, Kuzman M, Benetti F, Silva FJ, Allickson JG: Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell transplant 2008, 17(3):303-311.
  • [12]Yang ZX, Han Z-B, Ji YR, Wang YW, Liang L, Chi Y, Han ZC: CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties. PloS one 2013, 8(3):e59354.
  • [13]Pittenger MF, Martin BJ: Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004, 95(1):9-20.
  • [14]Sugiyama T, Kohara H, Noda M, Nagasawa T: Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 2006, 25(6):977-988.
  • [15]Anthony BA, Link DC: Regulation of hematopoietic stem cells by bone marrow stromal cells. Trends Immunol 2014, 35(1):32-37.
  • [16]Greenbaum A, Hsu YMS, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, Link DC: CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 2013, 495(7440):227-230.
  • [17]Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI: Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant 1995, 16(4):557-564.
  • [18]Koç ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM: Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 2000, 18(2):307-316.
  • [19]Zhou Y, Yuan J, Zhou B, Lee AJ, Lee AJ, Ghawji M, Yoo TJ: The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology 2011, 133(1):133-140.
  • [20]Kavanagh H, Mahon BP: Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 2011, 66(4):523-531.
  • [21]Zanone MM, Favaro E, Miceli I, Grassi G, Camussi E, Caorsi C, Camussi G: Human mesenchymal stem cells modulate cellular immune response to islet antigen glutamic acid decarboxylase in type 1 diabetes. J Clin Endocrinol Metab 2010, 95(8):3788-3797.
  • [22]Rafei M, Birman E, Forner K, Galipeau J: Allogeneic mesenchymal stem cells for treatment of experimental autoimmune encephalomyelitis. Mol Ther 2009, 17(10):1799-1803.
  • [23]Ding Y, Bushell A, Wood KJ: Mesenchymal stem-cell immunosuppressive capabilities: therapeutic implications in islet transplantation. Transplantation 2010, 89(3):270-273.
  • [24]González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M: Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 2009, 60(4):1006-1019.
  • [25]González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M: Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology 2009, 136(3):978-989.
  • [26]Ryan JM, Barry FP, Murphy JM, Mahon BP: Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (London, England) 2005, 2(8):11.
  • [27]Kim SJ, Moon GJ, Chang WH, Kim Y-H, Bang OY: Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial. Trials 2013, 14(1):317-328.
  • [28]Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY: Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Stem cells (Dayton, Ohio) 2010, 28:1099-1106.
  • [29]Bang OY, Lee JS, Lee PH, Lee G: Autologous mesenchymal stem cell transplantation in stroke patients. Annals of neurolog 2005, 57(6):874-882.
  • [30]Bhasin A, Srivastava MVP, Mohanty S, Bhatia R, Kumaran SS, Bose S: Stem cell therapy: a clinical trial of stroke. Clin neurol neurosurgery Stem cells (Dayton, Ohio) 2010, 115(7):1003-1008.
  • [31]Bartunek J, Behfar A, Dolatabadi D, Vanderheyden M, Ostojic M, Dens J, Terzic A: Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failure) multicenter randomized trial with lineage-specified biologics. J American Coll Cardiol 2013, 61(23):2329-2338.
  • [32]Yang Z, Zhang F, Ma W, Chen B, Zhou F, Xu Z, Zhang Y: A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery. Cardiovascr Ther 2010, 28(6):380-385.
  • [33]Weiss DJ, Casaburi R, Flannery R, Leroux-Williams M, Tashkin DP: A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 2013, 143(6):1590-1598.
  • [34]Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Wang FS: Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med 2012, 1(10):725-731.
  • [35]Horwitz EM, Gordon PL, Koo WKK, Marx JC, Neel MD, McNall RY, Hofmann T: Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci USA 2002, 99(13):8932-8937.
  • [36]Koç ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W: Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 2002, 30(4):215-222.
  • [37]Ichim TE, Alexandrescu DT, Solano F, Lara F, Campion RDN, Paris E, Riordan NH: Mesenchymal stem cells as anti-inflammatories: implications for treatment of Duchenne muscular dystrophy. Cell Immunol 2010, 260(2):75-82.
  • [38]Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Field LJ: Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004, 428(6983):664-668.
  • [39]Wang C, Cheng L, Xu H, Liu Z: Towards whole-body imaging at the single cell level using ultra-sensitive stem cell labeling with oligo-arginine modified upconversion nanoparticles. Biomaterials 2012, 33(19):4872-4881.
  • [40]Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Dzau VJ: Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005, 11(4):367-368.
  • [41]Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, Dzau VJ: Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J 2006, 20(6):661-669.
  • [42]Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Prockop DJ: Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009, 5(1):54-63.
  • [43]Shabbir A, Zisa D, Suzuki G, Lee T: Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen. Am J Physiol Heart Circ Physiol 2009, 296(6):H1888-H1897.
  • [44]Yang CC, Shih YH, Ko MH, Hsu SY, Cheng H, Fu YS: Transplantation of human umbilical mesenchymal stem cells from Wharton¿s jelly after complete transection of the rat spinal cord. PloS one 2008, 3(10):e3336.
  • [45]Song M, Heo J, Chun JY, Bae HS, Kang JW, Kang H, Choo MS: The paracrine effects of mesenchymal stem cells stimulate the regeneration capacity of endogenous stem cells in the repair of a bladder-outlet-obstruction-induced overactive bladder. Stem Cells Dev 2014, 23(6):654-663.
  • [46]Ahluwalia A, Tarnawski AS: Critical role of hypoxia sensor - HIF-1? in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr Med Chem 2012, 19(1):90-97.
  • [47]Imtiyaz HZ, Simon MC: Hypoxia-inducible factors as essential regulators of inflammation. Curr Top Microbiol Immunol 2010, 345:105-120.
  • [48]Hawkins KE, Sharp TV, McKay TR: The role of hypoxia in stem cell potency and differentiation. Regen Med 2013, 8(6):771-782.
  • [49]Berniakovich I, Giorgio M: Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells. Int J Mol Sci 2013, 14(1):2119-2134.
  • [50]Youn SW, Lee SW, Lee J, Jeong HK, Suh JW, Yoon CH, Kim HS: COMP-Ang1 stimulates HIF-1?-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood 2011, 117:4376-4386.
  • [51]Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Gurtner GC: Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 2004, 10(8):858-864.
  • [52]Crisostomo PR, Wang Y, Markel TA, Wang M, Lahm T, Meldrum DR: Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. Am J Physiol Cell Physiol 2008, 294(3):C675-C682. doi:10.1152/ajpcell.00437.2007
  • [53]Rasmussen JG, Frøbert O, Pilgaard L, Kastrup J, Simonsen U, Zachar V, Fink T: Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells. Cytotherapy 2011, 13(3):318-328.
  • [54]Yust-Katz S, Fisher-Shoval Y, Barhum Y, Ben-Zur T, Barzilay R, Lev N, Offen D: Placental mesenchymal stromal cells induced into neurotrophic factor-producing cells protect neuronal cells from hypoxia and oxidative stress. Cytotherapy 2012, 14(1):45-55.
  • [55]Iida K, Takeda-Kawaguchi T, Tezuka Y, Kunisada T, Shibata T, Tezuka K: Hypoxia enhances colony formation and proliferation but inhibits differentiation of human dental pulp cells. Archi Oral Biol 2010, 55(9):648-654.
  • [56]Efimenko A, Starostina E, Kalinina N, Stolzing A: Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med 2011, 9(1):10.
  • [57]Chang CP, Chio CC, Cheong CU, Chao CM, Cheng BC, Lin MT: Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci (Lond) 2013, 124(3):165-176.
  • [58]Yu J, Yin S, Zhang W, Gao F, Liu Y, Chen Z, Zheng S: Hypoxia preconditioned bone marrow mesenchymal stem cells promoted liver regeneration in a rat massive hepatectomy model. Stem Cell Res Ther 2013, 4(4):83.
  • [59]Li JH, Zhang N, Wang JA: Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic pre-conditioning in diabetic cardiomyopathy. J Endocrinol Invest 2008, 31(2):103-110.
  • [60]Haque N, Rahman MT, Abu Kasim NH, Alabsi AM: Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy.Scientific World Journal 2013 Artic 2013,(12): eCollection.
  • [61]Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Ringdén O: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008, 371(9624):1579-1586.
  • [62]Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Chen H: The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 2008, 22(2):593-599.
  • [63]Ball L, Bredius R, Lankester A, Schweizer J, van den Heuvel-Eibrink M, Escher H, Egeler M: Third party mesenchymal stromal cell infusions fail to induce tissue repair despite successful control of severe grade IV acute graft-versus-host disease in a child with juvenile myelo-monocytic leukemia. Leukemia 2008, 22(6):1256-1257.
  • [64]Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, Le Blanc K: Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006, 81(10):1390-1397.
  • [65]Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O: Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004, 363(9419):1439-1441.
  • [66]Müller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F, Handgretinger R: Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells, Mol Dis 2008, 40(1):25-32.
  • [67]Roemeling-Van Rhijn M, Mensah FKF, Korevaar SS, Leijs MJC, Van Osch GJVM, IJzermans JNM, Hoogduijn MJ: Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells. Front Immunol 2013, 4(203):8.
  • [68]English K, Tonlorenzi R, Cossu G, Wood KJ: Mesoangioblasts suppress T cell proliferation through IDO and PGE-2-dependent pathways. Stem Cells Dev 2013, 22(3):512-523.
  • [69]Engela AU, Baan CC, Peeters AM, Weimar W, Hoogduijn MJ: Interaction between adipose-tissue derived mesenchymal stem cells and regulatory T cells. Cell Transplant 2013, 22(1):41-54.
  • [70]Jui HY, Lin CH, Hsu WT, Liu YR, Hsu RB, Chiang BL, Lee CM: Autologous mesenchymal stem cells prevent transplant arteriosclerosis by enhancing local expression of interleukin-10, interferon-?, and indoleamine 2,3-dioxygenase. Cell Transplant 2012, 21(5):971-984.
  • [71]Huang WH, Chen HL, Huang PH, Yew TL, Lin MW, Lin SJ, Hung SC: Hypoxic mesenchymal stem cells engraft and ameliorate limb ischaemia in allogeneic recipients. Cardiovasc Res 2014, 101(2):266-276.
  • [72]Skurkovich B, Skurkovich S: Anti-interferon-gamma antibodies in the treatment of autoimmune diseases. Curr Opin Mol Ther 2003, 5(1):52-57.
  • [73]Rong LJ, Chi Y, Yang SG, Chen DD, Chen F, Xu SX, Han ZC: [Effects of interferon-? on biological characteristics and immunomodulatory property of human umbilical cord-derived mesenchymal stem cells]. Zhongguo shi yan xue ye xue za zhi = J Exp hematology / Chin Assoc Pathophysiol 2012, 20(2):421-426.
  • [74]Kang JW, Koo HC, Hwang SY, Kang SK, Ra JC, Lee MH, Park YH: Immunomodulatory effects of human amniotic membrane-derived mesenchymal stem cells. J Vet Sci 2012, 13(1):23-31.
  • [75]Lin W, Oh SKW, Choo ABH, George AJT: Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived mesenchymal stromal cells through a feedback mechanism. Cytotherapy 2012, 14(3):274-284.
  • [76]Croitoru-Lamoury J, Lamoury FMJ, Caristo M, Suzuki K, Walker D, Takikawa O, Brew BJ: Interferon-? regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO). PloS one 2011, 6(2):e14698. doi:10.1371/journal.pone.0014698
  • [77]Tu Z, Li Q, Bu H, Lin F: Mesenchymal stem cells inhibit complement activation by secreting factor H. Stem Cells Dev 2010, 19(11):1803-1809.
  • [78]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(2):353-363.
  • [79]Noone C, Kihm A, English K, O¿Dea S, Mahon BP: IFN-gamma stimulated human umbilical-tissue derived cells potently suppress NK activation and resist NK mediated cytotoxicity in vitro. Stem Cells Dev 2013, 15(22):3003-3014.
  • [80]Gieseke F, Kruchen A, Tzaribachev N, Bentzien F, Dominici M, Müller I: Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation. Europ J Immunol 2013, 43(10):2741-2749.
  • [81]Kwon YW, Heo SC, Jeong GO, Yoon JW, Mo WM, Lee MJ, Kim JH: Tumor necrosis factor-?-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis. Biochim Biophys Acta 2013, 1832(12):2136-2144.
  • [82]Lu Z, Wang G, Dunstan CR, Chen Y, Lu WYR, Davies B, Zreiqat H: Activation and promotion of adipose stem cells by tumour necrosis factor-alpha preconditioning for bone regeneration. J Cell Physiol 2013, 228(8):1737-1744.
  • [83]Grote K, Petri M, Liu C, Jehn P, Spalthoff S, Kokemüller H, Jagodzinski M: Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors. Europ Cells Mater 2013, 26:66-79. discussion 79
  • [84]Bessout R, Sémont A, Demarquay C, Charcosset A, Benderitter M, Mathieu N: Mesenchymal stem cell therapy induces glucocorticoid synthesis in colonic mucosa and suppresses radiation-activated T cells: new insights into MSC immunomodulation. Mucosal Immunol 2014, 7(3):656-669.
  • [85]Bartosh TJ, Ylöstalo JH, Mohammadipoor A, Bazhanov N, Coble K, Claypool K, Prockop DJ: Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci USA 2010, 107(31):13724-13729.
  • [86]Ylöstalo JH, Bartosh TJ, Coble K, Prockop DJ: Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells 2012, 30(10):2283-2296.
  • [87]Bartosh TJ, Ylöstalo JH, Bazhanov N, Kuhlman J, Prockop DJ: Dynamic compaction of human mesenchymal stem/precursor cells into spheres self-activates caspase-dependent IL1 signaling to enhance secretion of modulators of inflammation and immunity (PGE2, TSG6, and STC1). Stem Cells 2013, 31(11):2443-2456.
  • [88]Frith JE, Thomson B, Genever PG: Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng Part C Methods 2010, 16(4):735-749.
  • [89]Nakamura T: Structure and function of hepatocyte growth factor. Progr Growth Factor Res 1991, 3(1):67-85.
  • [90]Lefebvre J, Ancot F, Leroy C, Muharram G, Lemiere A, Tulasne D: Met degradation: more than one stone to shoot a receptor down. FASEB J 2012, 26(4):1387-1399.
  • [91]Roletto F, Galvani AP, Cristiani C, Valsasina B, Landonio A, Bertolero F: Basic fibroblast growth factor stimulates hepatocyte growth factor/scatter factor secretion by human mesenchymal cells. J Cell Physiol 1996, 166(1):105-111.
  • [92]Wilson SE, Walker JW, Chwang EL, He YG: Hepatocyte growth factor, keratinocyte growth factor, their receptors, fibroblast growth factor receptor-2, and the cells of the cornea. Invest Ophthalmol Vis Sci 1993, 34(8):2544-2561.
  • [93]Watanabe S, Hirose M, Wang XE, Maehiro K, Murai T, Kobayashi O, Sato N: Hepatocyte growth factor accelerates the wound repair of cultured gastric mucosal cells. Biochem Biophys Res Commun 1994, 199(3):1453-1460.
  • [94]Pyun WB, Hahn W, Kim DS, Yoo WS, Lee SD, Won JH, Kim S: Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia. Gene Ther 2010, 17(12):1442-1452.
  • [95]Morishita R, Makino H, Aoki M, Hashiya N, Yamasaki K, Azuma J, Ogihara T: Phase I/IIa clinical trial of therapeutic angiogenesis using hepatocyte growth factor gene transfer to treat critical limb ischemia. Arterioscler Thromb, Vasc Biol 2011, 31(3):713-720.
  • [96]Shigematsu H, Yasuda K, Sasajima T, Takano T, Miyata T, Ohta T, Morishita R: Transfection of human HGF plasmid DNA improves limb salvage in Buerger¿s disease patients with critical limb ischemia. International Angiol 2011, 30(2):140-149.
  • [97]Rutella S, Danese S, Leone G: Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 2006, 108(5):1435-1440.
  • [98]Benkhoucha M, Santiago-Raber ML, Schneiter G, Chofflon M, Funakoshi H, Nakamura T, Lalive PH: Hepatocyte growth factor inhibits CNS autoimmunity by inducing tolerogenic dendritic cells and CD25?+?Foxp3+ regulatory T cells. Proc Natl Acad Sci USA 2010, 107(14):6424-6429.
  • [99]Okunishi K, Dohi M, Fujio K, Nakagome K, Tabata Y, Okasora T, Yamamoto K: Hepatocyte growth factor significantly suppresses collagen-induced arthritis in mice. J Immunol 2011, 179(8):5504-5513.
  • [100]Bai L, Lennon DP, Caplan AI, DeChant A, Hecker J, Kranso J, Miller RH: Hepatocyte growth factor mediates mesenchymal stem cell¿induced recovery in multiple sclerosis models. Nat Neurosci 2012, 15(6):862-870.
  • [101]Lu S, Lu C, Han Q, Li J, Du Z, Liao L, Zhao RC: Adipose-derived mesenchymal stem cells protect PC12 cells from glutamate excitotoxicity-induced apoptosis by upregulation of XIAP through PI3-K/Akt activation. Toxicology 2011, 279(1¿3):189-195.
  • [102]Yasuda K, Ozaki T, Saka Y, Yamamoto T, Gotoh M, Ito Y, Maruyama S: Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells. Cytotherapy 2012, 14(9):1089-1100.
  • [103]Mishra L, Derynck R, Mishra B: Transforming growth factor-beta signaling in stem cells and cancer. Science 2005, 310(5745):68-71.
  • [104]Verrecchia F, Mauviel A: Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol 2002, 118(2):211-215.
  • [105]Whiteside TL: What are regulatory T cells (Treg) regulating in cancer and why? Semin Cancer Biol 2012, 22(4):327-334.
  • [106]Smith AL, Robin TP, Ford HL: Molecular pathways: targeting the TGF- pathway for cancer therapy. Clin Cancer Res 2012, 18(17):4514-4521.
  • [107]Raghupathy R: Pregnancy: success and failure within the Th1/Th2/Th3 paradigm. Semin Immunol 2001, 13(4):219-227.
  • [108]Ohta K, Yamagami S, Taylor AW, Streilein JW: IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 2000, 41(9):2591-2599.
  • [109]Tompkins AB, Hutchinson P, De Kretser DM, Hedger MP: Characterization of lymphocytes in the adult rat testis by flow cytometry: effects of activin and transforming growth factor beta on lymphocyte subsets in vitro. Biol Reprod 1998, 58(4):943-951.
  • [110]Gandhi R, Anderson DE, Weiner HL: Cutting Edge: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner. J Immunol 2007, 178(7):4017-4021.
  • [111]Kushwah R, Wu J, Oliver JR, Jiang G, Zhang J, Siminovitch KA, Hu J: Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg. Eur J Immunol 2010, 40(4):1022-1035.
  • [112]Romagnani S: Human Th17 cells. Arthritis rRes Ther 2008, 10(2):206.
  • [113]Melief SM, Zwaginga JJ, Fibbe WE, Roelofs H: Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts. Stem Cells Transl Med 2013, 2(6):455-463.
  • [114]Miguel M: Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012, 12(5):574-591.
  • [115]Zhou C, Yang B, Tian Y, Jiao H, Zheng W, Wang J, Guan F: Immunomodulatory effect of human umbilical cord Wharton¿s jelly-derived mesenchymal stem cells on lymphocytes. Cell Immunol 2011, 272(1):33-38.
  • [116]Zhao ZG, Li WM, Chen ZC, You Y, Zou P: Immunosuppressive properties of mesenchymal stem cells derived from bone marrow of patients with chronic myeloid leukemia. Immunol Invest 2008, 37(7):726-739.
  • [117]Yoo SW, Chang DY, Lee HS, Kim GH, Park JS, Ryu BY, Suh-Kim H: Immune following suppression mesenchymal stem cell transplantation in the ischemic brain is mediated by TGF-? Neurobiol Dis 2013, 58:249-257.
  • [118]Ye Z, Wang Y, Xie HY, Zheng SS: Immunosuppressive effects of rat mesenchymal stem cells: involvement of CD4?+?CD25+ regulatory T cells. Hepatobiliary Pancreat Dis Int 2008, 7(6):608-614.
  • [119]Connolly DT: Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 1991, 47(3):219-223.
  • [120]Razban V, Lotfi AS, Soleimani M, Ahmadi H, Massumi M, Khajeh S, Khoshdel A: HIF-1? overexpression induces angiogenesis in mesenchymal stem cells. Biores Open Access 2012, 1(4):174-183.
  • [121]Semeraro F, Morescalchi F, Duse S, Parmeggiani F, Gambicorti E, Costagliola C: Aflibercept in wet AMD: specific role and optimal use. Drug Des, Devel Ther 2013, 7:711-722.
  • [122]Chen CT, Hung MC: Beyond anti-VEGF: dual-targeting antiangiogenic and antiproliferative therapy. Am J Transl Res 2013, 5(4):393-403.
  • [123]Mughal NA, Russell DA, Ponnambalam S, Homer-Vanniasinkam S: Gene therapy in the treatment of peripheral arterial disease. Br J Surg 2012, 99(1):6-15.
  • [124]Chawla PS, Keelan MH, Kipshidze N: Angiogenesis for the treatment of vascular diseases. Int Angiol 1999, 18(3):185-192.
  • [125]Kagiwada H, Yashiki T, Ohshima A, Tadokoro M, Nagaya N, Ohgushi H: Human mesenchymal stem cells as a stable source of VEGF-producing cells. J Tissue Eng Regen Med 2008, 2(4):184-189.
  • [126]Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, Phillips MI: Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 2004, 117(1):3-10.
  • [127]Halkos ME, Zhao ZQ, Kerendi F, Wang NP, Jiang R, Schmarkey LS, Vinten-Johansen J: Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction. Basic Res Cardiol 2008, 103(6):525-536.
  • [128]Shyu KG, Wang BW, Hung HF, Chang CC, Shih DTB: Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. J Biomed Sci 2006, 13(1):47-58.
  • [129]Luo H, Zhang Y, Zhang Z, Jin Y: The protection of MSCs from apoptosis in nerve regeneration by TGF?1 through reducing inflammation and promoting VEGF-dependent angiogenesis. Biomaterials 2012, 33(17):4277-4287.
  • [130]Hayashi Y, Tsuji S, Tsujii M, Nishida T, Ishii S, Iijima H, Kawano S: Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 2008, 294(3):G778-G786.
  • [131]Ili? D, Almeida EA, Schlaepfer DD, Dazin P, Aizawa S, Damsky CH: Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J Cell Biol 1998, 143(2):547-560.
  • [132]Gerber HP, Dixit V, Ferrara N: Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 1998, 273(21):13313-13316.
  • [133]Tachi Y, Fukui D, Wada Y, Koshikawa M, Shimodaira S, Ikeda U, Amano J: Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia. Expert Opin Biol Ther 2008, 8(6):705-712.
  • [134]Wisniewski HG, Vilcek J: TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity. Cytokine Growth Factor Rev 1997, 8(2):143-156.
  • [135]Wisniewski H-G, Vilcek J: Cytokine-induced gene expression at the crossroads of innate immunity, inflammation and fertility: TSG-6 and PTX3/TSG-14. Cytokine Growth Factor Rev 2004, 15(2¿3):129-146.
  • [136]Lin QM, Zhao S, Zhou LL, Fang XS, Fu Y, Huang ZT: Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia: contribution of TNF-?-induced protein 6. Acta Pharmacol Sin 2013, 34(6):784-792.
  • [137]Kota DJ, Wiggins LL, Yoon N, Lee RH: TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity. Diabetes 2013, 62(6):2048-2058.
  • [138]Wang N, Shao Y, Mei Y, Zhang L, Li Q, Li D, Chen X: Novel mechanism for mesenchymal stem cells in attenuating peritoneal adhesion: accumulating in the lung and secreting tumor necrosis factor ?-stimulating gene-6. Stem Cell Res Ther 2012, 3(6):51.
  • [139]Wang N, Li Q, Zhang L, Lin H, Hu J, Li D, Chen X: Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6. PLoS ONE 2012, 7(8):e43768.
  • [140]Fisher-Shoval Y, Barhum Y, Sadan O, Yust-Katz S, Ben-Zur T, Lev N, Offen D: Transplantation of placenta-derived mesenchymal stem cells in the EAE mouse model of MS. J Mol Neurosci 2012, 48(1):176-184.
  • [141]Lee JJ, Takei M, Hori S, Inoue Y, Harada Y, Tanosaki R, Kakizoe T: The role of PGE(2) in the differentiation of dendritic cells: how do dendritic cells influence T-cell polarization and chemokine receptor expression? Stem Cells 2002, 20(5):448-459.
  • [142]Zhang Y, Liu Q, Zhang M, Yu Y, Liu X, Cao X: Fas signal promotes lung cancer growth by recruiting myeloid-derived suppressor cells via cancer cell-derived PGE2. J Immunol 2009, 182(6):3801-3808.
  • [143]Eruslanov E, Daurkin I, Ortiz J, Vieweg J, Kusmartsev S: Pivotal Advance: Tumor-mediated induction of myeloid-derived suppressor cells and M2-polarized macrophages by altering intracellular PGE catabolism in myeloid cells. J leukoc Biol 2010, 88(5):839-848.
  • [144]Eruslanov E, Daurkin I, Vieweg J, Daaka Y, Kusmartsev S: Aberrant PGE metabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells. Int immunopharmacol 2011, 11(7):848-855.
  • [145]Obermajer N, Muthuswamy R, Lesnock J, Edwards RP, Kalinski P: Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 2011, 118(20):5498-5505.
  • [146]Goto T, Herberman RB, Maluish A, Strong DM: Cyclic AMP as a mediator of prostaglandin E-induced suppression of human natural killer cell activity. J Immunol 1983, 130(3):1350-1355.
  • [147]Smith RJ: Modulation of phagocytosis by and lysosomal enzyme secretion from guinea-pig neutrophils: effect of nonsteroid anti-inflammatory agents and prostaglindins. J Pharmacol Exper Ther 1977, 200(3):647-657.
  • [148]Kali?ski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML: IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 1997, 159(1):28-35.
  • [149]Snijdewint FG, Kali?ski P, Wierenga EA, Bos JD, Kapsenberg ML: Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J Immunol 1993, 150(12):5321-5329.
  • [150]Baratelli F, Lin Y, Zhu L, Yang S-C, Heuzé-Vourc¿h N, Zeng G, Dubinett SM: Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol 2005, 175(3):1483-1490.
  • [151]Németh K, Leelahavanichkul A, Yuen PST, Mayer B, Parmelee A, Doi K, Mezey E: Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009, 15(1):42-49.
  • [152]Zhang Y, Cai W, Huang Q, Gu Y, Shi Y, Huang J, Zhang Y: Mesenchymal stem cells alleviate bacteria-induced liver injury in mice by inducing regulatory dendritic cells. Hepatology 2013, 59(2):671-682.
  • [153]Dhingra S, Li P, Huang XP, Guo J, Wu J, Mihic A, Li RK: Preserving prostaglandin E2 level prevents rejection of implanted allogeneic mesenchymal stem cells and restores postinfarction ventricular function. Circulation 2013, 128(11 Suppl 1):S69-S78.
  • [154]Parolini O, Lombardi G, Cargnoni A, Rossi D, Arienti D, Ressel L, Poli A: Medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis. Cytotherapy 2012, 14(2):153-161.
  • [155]Barondes SH, Cooper DN, Gitt MA, Leffler H: Galectins. Structure and function of a large family of animal lectins. J Biol Chem 1994, 269(33):20807-20810.
  • [156]Gieseke F, Böhringer J, Bussolari R, Dominici M, Handgretinger R, Müller I: Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood 2010, 116(19):3770-3779.
  • [157]Quesenberry PJ, Aliotta JM: The paradoxical dynamism of marrow stem cells: considerations of stem cells, niches, and microvesicles. Stem Cell Rev 2008, 4(3):137-147.
  • [158]Fierabracci A, Del Fattore A, Luciano R, Muraca M, Teti A, Muraca M: Recent advances in mesenchymal stem cell immunomodulation. The role of microvesicles.Cell transplantat 2013, [Epub ahead of print].
  • [159]Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, Camussi G: Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol 2009, 20(5):1053-1067.
  • [160]Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, Camussi G: Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant 2012, 26(5):1474-1483.
  • [161]Zhang HC, Liu XB, Huang S, Bi XY, Wang HX, Xie LX, Guo ZK: Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo. Stem Cells Dev 2012, 21(18):3289-3297.
  • [162]Zhu YG, Feng XM, Abbott J, Fang XH, Hao Q, Monsel A, Lee JW: Human mesenchymal stem cell microvesicles for treatment of E. coli endotoxin-induced acute lung injury in mice. Stem cells 2014, 32(1):116-125.
  • [163]Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, Bhattacharya J: Mitochondrial transfer from bone-marrow¿derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med 2012, 18(5):759-765.
  • [164]Théry C, Ostrowski M, Segura E: Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 2009, 9(8):581-593.
  • [165]Ludwig AK, Giebel B: Exosomes: Small vesicles participating in intercellular communication. Int J Biochem Cell Biol 2012, 44(1):11-15.
  • [166]Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJA, Cooper JM: Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 2011, 42(3):360-367.
  • [167]Silverman JM, Reiner NE: Exosomes and other microvesicles in infection biology: organelles with unanticipated phenotypes. Cell Microbiol 2011, 13(1):1-9.
  • [168]Pan BT, Johnstone RM: Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 1983, 33(3):967-978.
  • [169]Alonso R, Mazzeo C, Rodriguez MC, Marsh M, Fraile-Ramos A, Calvo V, Izquierdo M: Diacylglycerol kinase ? regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes. Cell death Differ 2011, 18(7):1161-1173.
  • [170]Zhang H, Xie Y, Li W, Chibbar R, Xiong S, Xiang J: CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity. Cell Mol Immunol 2011, 8(1):23-30.
  • [171]Mathews JA, Gibb DR, Chen BH, Scherle P, Conrad DH: CD23 Sheddase A disintegrin and metalloproteinase 10 (ADAM10) is also required for CD23 sorting into B cell-derived exosomes. J Biol Chem 2010, 285(48):37531-37541.
  • [172]Buschow SI, Van Balkom BWM, Aalberts M, Heck AJR, Wauben M, Stoorvogel W: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol Cell Biol 2010, 88(8):851-856.
  • [173]Hwang I, Ki D: Receptor-mediated T cell absorption of antigen presenting cell-derived molecules. Front Biosci 2011, 16:411-421.
  • [174]Viaud S, Ploix S, Lapierre V, Théry C, Commere PH, Tramalloni D, Chaput N: Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-? J Immunother 2011, 34(1):65-75.
  • [175]Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z: Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol 2011, 187(2):676-683.
  • [176]Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, Zeidler R: Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother 2011, 60(5):639-648.
  • [177]Lachenal G, Pernet-Gallay K, Chivet M, Hemming FJ, Belly A, Bodon G, Sadoul R: Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol Cell Neurosci 2011, 46(2):409-418.
  • [178]Fauré J, Lachenal G, Court M, Hirrlinger J, Chatellard-Causse C, Blot B, Sadoul R: Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 2006, 31(4):642-648.
  • [179]Fitzner D, Schnaars M, Van Rossum D, Krishnamoorthy G, Dibaj P, Bakhti M, Simons M: Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 2011, 124(Pt 3):447-458.
  • [180]Mincheva-Nilsson L, Baranov V: The role of placental exosomes in reproduction. Am J Reprod Immunol 2010, 63(6):520-533.
  • [181]Mincheva-Nilsson L, Nagaeva O, Chen T, Stendahl U, Antsiferova J, Mogren I, Baranov V: Placenta-derived soluble MHC class I chain-related molecules down-regulate NKG2D receptor on peripheral blood mononuclear cells during human pregnancy: a possible novel immune escape mechanism for fetal survival. J Immunol 2006, 176(6):3585-3592.
  • [182]Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor ENE, De Kleijn DP: Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 2013, 10(3):301-312.
  • [183]Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Xu W: Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013, 22(6):845-854.
  • [184]Tomasoni S, Longaretti L, Rota C, Morigi M, Conti S, Gotti E, Benigni A: Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells. Stem Cells Dev 2012, 22(5):772-780.
  • [185]Raymond A, Ensslin MA, Shur BD: SED1/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions. J Cell Biochem 2009, 106(6):957-966.
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