Immunomodulatory effects of mesenchymal stromal cells revisited in the context of inflammatory cardiomyopathy

Stem Cells International

Volumn , Issue , 2013, Pages

  Miteva, Kapka ^a   Van Linthout, Sophie ^a   Volk, Hans Dieter ^a   Tschöpe, Carsten ^a,b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; CELL REGENERATION; CELL TRANSPLANTATION; CYTOKINE RESPONSE; DENDRITIC CELL; HUMAN; IMMUNE SYSTEM; IMMUNOMODULATION; IMMUNOPATHOLOGY; INNATE IMMUNITY; MACROPHAGE; MESENCHYMAL STROMA CELL; MYOCARDITIS; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW; TH1 TH2 BALANCE; TH17 CELL; THERAPY EFFECT; TREATMENT INDICATION;

EID: 84880168367     PISSN: None     EISSN: 16879678     Source Type: Journal    
DOI: 10.1155/2013/353097     Document Type: Review

References (188)

1. Richardson P., McKenna R. W., Bristow M., Maisch B., Mautner B., O'Connell J., Olsen E., Thiene G., Goodwin J., Gyarfas I., Martin I., Nordet P., Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996 93 5 841 842 2-s2.0-0029864693
2. Aretz H. T., Billingham M. E., Edwards W. D., Factor S. M., Fallon J. T., Fenoglio J. J., Olsen E. G., Schoen F. J., Myocarditis. A histopathologic definition and classification. The American Journal of Cardiovascular Pathology 1987 1 1 3 14 2-s2.0-0023069681
3. Feldman A. M., McNamara D., Myocarditis. The New England Journal of Medicine 2000 343 19 1388 1398 10.1056/NEJM200011093431908
4. Bowles N. E., Ni J., Kearney D. L., Pauschinger M., Schultheiss H. P., McCarthy R., Hare J., Bricker J. T., Bowles K. R., Towbin J. A., Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adults. Journal of the American College of Cardiology 2003 42 3 466 472 2-s2.0-10744222678 10.1016/S0735-1097(03)00648-X
5. Pauschinger M., Doerner A., Kuehl U., Schwimmbeck P. L., Poller W., Kandolf R., Schultheiss H. P., Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation 1999 99 7 889 895 2-s2.0-0033596659
6. Tschöpe C., Bock C. T., Kasner M., Noutsias M., Westermann D., Schwimmbeck P. L., Pauschinger M., Poller W. C., Kühl U., Kandolf R., Schultheiss H. P., High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction. Circulation 2005 111 7 879 886 2-s2.0-20044374676 10.1161/01.CIR.0000155615.68924.B3
7. Pankuweit S., Moll R., Baandrup U., Portig I., Hufnagel G., Maisch B., Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Human Pathology 2003 34 5 497 503 2-s2.0-0037605977 10.1016/S0046-8177(03)00078- 9
8. Kühl U., Pauschinger M., Bock T., Klingel K., Schwimmbeck C. P. L., Seeberg B., Krautwurm L., Poller W., Schultheiss H. P., Kandolf R., Parvovirus B19 infection mimicking acute myocardial infarction. Circulation 2003 108 8 945 950 2-s2.0-0042358760 10.1161/01.CIR.0000085168.02782.2C
9. D'Ambrosio A., Patti G., Manzoli A., Di Sciascio G., Sinagra G., Di Lenarda A., Silvestri F., The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart 2001 85 5 499 504 2-s2.0-0034763492
10. Roger V. L., Go A. S., Lloyd-Jones D. M., Adams R. J., Berry J. D., Brown T. M., Carnethon M. R., Dai S., de Simone G., Ford E. S., Fox C. S., Fullerton H. J., Gillespie C., Greenlund K. J., Hailpern S. M., Heit J. A., Ho P. M., Howard V. J., Kissela B. M., Kittner S. J., Lackland D. T., Lichtman J. H., Lisabeth L. D., Makuc D. M., Marcus G. M., Marelli A., Matchar D. B., McDermott M. M., Meigs J. B., Moy C. S., Mozaffarian D., Mussolino M. E., Nichol G., Paynter N. P., Rosamond W. D., Sorlie P. D., Stafford R. S., Turan T. N., Turner M. B., Wong N. D., Wylie-Rosett J., Heart disease and stroke statistics-2011 update: a report from the American Heart Association. Circulation 2011 123 4 e18 e209 10.1161/CIR.0b013e3182009701
11. Lloyd-Jones D. M., Larson M. G., Leip E. P., Beiser A., D'Agostino R. B., Kannel W. B., Murabito J. M., Vasan R. S., Benjamin E. J., Levy D., Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation 2002 106 24 3068 3072 2-s2.0-0037058826 10.1161/01.CIR.0000039105. 49749.6F
12. Frustaci A., Russo M. A., Chimenti C., Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. European Heart Journal 2009 30 16 1995 2002 2-s2.0-68949154620 10.1093/eurheartj/ehp249
13. Maisch B., Hufnagel G., Kölsch S., Funck R., Richter A., Rupp H., Herzum M., Pankuweit S., Treatment of inflammatory dilated cardiomyopathy and (peri)myocarditis with immunosuppression and i.v. immunoglobulins. Herz 2004 29 6 624 636 2-s2.0-5444253501 10.1007/s00059-004-2628-7
14. Late-Breaking Clinical Trial Abstracts. Circulation 2008 118 22 2309 2317 10.1161/CIRCULATIONAHA.108.191458
15. Wang Y. X., da Cunha V., Vincelette J., White K., Velichko S., Xu Y., Gross C., Fitch R. M., Halks-Miller M., Larsen B. R., Yajima T., Knowlton K. U., Vergona R., Sullivan M. E., Croze E., Antiviral and myocyte protective effects of murine interferon- β and-α 2 in coxsackievirus B3-induced myocarditis and epicarditis in Balb/c mice. American Journal of Physiology-Heart and Circulatory Physiology 2007 293 1 H69 H76 2-s2.0-34547126674 10.1152/ajpheart.00154.2007
16. Kühl U., Pauschinger M., Schwimmbeck P. L., Seeberg B., Lober C., Noutsias M., Poller W., Schultheiss H. P., Interferon- β treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 2003 107 22 2793 2798 2-s2.0-0038120010 10.1161/01.CIR.0000072766.67150.51
17. Schmidt-Lucke C., Spillmann F., Bock T., Kühl U., van Linthout S., Schultheiss H. P., Tschöpe C., Interferon beta modulates endothelial damage in patients with cardiac persistence of human parvovirus B19 infection. Journal of Infectious Diseases 2010 201 6 936 945 2-s2.0-77749271186 10.1086/650700
18. Blauwet L. A., Cooper L. T., Antimicrobial agents for myocarditis: target the pathway, not the pathogen. Heart 2010 96 7 494 495 2-s2.0-77950582998 10.1136/hrt.2009.173740
19. Le Blanc K., Tammik L., Sundberg B., Haynesworth S. E., Ringdén O., Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scandinavian Journal of Immunology 2003 57 1 11 20 2-s2.0-0042740515 10.1046/j.1365-3083.2003.01176.x
20. Esfandiarei M., McManus B. M., Molecular biology and pathogenesis of viral myocarditis. Annual Review of Pathology 2008 3 127 155 10.1146/annurev.pathmechdis.3.121806.151534
21. Mason J. W., Myocarditis and dilated cardiomyopathy an inflammatory link. Cardiovascular Research 2003 60 1 5 10 10.1016/S0008-6363(03)00437-1
22. Kindermann I., Kindermann M., Kandolf R., Klingel K., Bültmann B., Müller T., Lindinger A., Böhm M., Predictors of outcome in patients with suspected myocarditis. Circulation 2008 118 6 639 648 10.1161/ CIRCULATIONAHA.108.769489
23. Woodruff J. F., Woodruff J. J., Involvement of T lymphocytes in the pathogenesis of coxsackie virus B3 heart disease. The Journal of Immunology 1974 113 6 1726 1734
24. Shi Y., Fukuoka M., Li G., Liu Y., Chen M., Konviser M., Chen X., Opavsky M. A., Liu P. P., Regulatory T cells protect mice against coxsackievirus- induced myocarditis through the transforming growth factor β -coxsackie-adenovirus receptor pathway. Circulation 2010 121 24 2624 2634 2-s2.0-77954086395 10.1161/CIRCULATIONAHA.109.893248
25. Li K., Xu W., Guo Q., Jiang Z., Wang P., Yue Y., Xiong S., Differential macrophage polarization in male and female BALB/c mice infected with coxsackievirus B3 defines susceptibility to viral myocarditis. Circulation Research 2009 105 4 353 364 2-s2.0-70349257967 10.1161/CIRCRESAHA.109.195230
26. Li J., Leschka S., Rutschow S., Schwimmbeck P. L., Husmann L., Noutsias M., Westermann D., Poller W., Zeichhardt H., Klingel K., Tschope C., Schultheiss H. P., Pauschinger M., Immunomodulation by interleukin-4 suppresses matrix metalloproteinases and improves cardiac function in murine myocarditis. European Journal of Pharmacology 2007 554 1 60 68 2-s2.0-33751436595 10.1016/j.ejphar.2006.08.024
27. Yajima T., Knowlton K. U., Viral myocarditis from the perspective of the virus. Circulation 2009 119 19 2615 2624 10.1161/CIRCULATIONAHA.108.766022
28. Mann D. L., The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls. Circulation Research 2011 108 9 1133 1145 10.1161/CIRCRESAHA.110.226936
29. Akira S., Sato S., Toll-like receptors and their signaling mechanisms. Scandinavian Journal of Infectious Diseases 2003 35 9 555 562 10.1080/00365540310015683
30. Seko Y., Takahashi N., Yagita H., Okumura K., Yazaki Y., Expression of cytokine mRNAs in murine hearts with acute myocarditis caused by coxsackievirus b3. The Journal of Pathology 1997 183 1 105 108 10.1002/(SICI)1096-9896(199709) 183:1<105::AID-PATH1094>3.0.CO;2-E
31. Fuse K., Chan G., Liu Y., Gudgeon P., Husain M., Chen M., Yeh W. C., Akira S., Liu P. P., Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of coxsackievirus B3-induced myocarditis and influences type I interferon production. Circulation 2005 112 15 2276 2285 2-s2.0-26844546302 10.1161/CIRCULATIONAHA.105.536433
32. Satoh M., Nakamura M., Akatsu T., Iwasaka J., Shimoda Y., Segawa I., Hiramori K., Expression of Toll-like receptor 4 is associated with enteroviral replication in human myocarditis. Clinical Science 2003 104 6 577 584 2-s2.0-0037777811 10.1042/CS20020263
33. Deonarain R., Cerullo D., Fuse K., Liu P. P., Fish E. N., Protective role for interferon- β in coxsackievirus B3 infection. Circulation 2004 110 23 3540 3543 2-s2.0-10044294907 10.1161/01.CIR.0000136824.73458.20
34. Kühl U., Lassner D., von Schlippenbach J., Poller W., Schultheiss H. P., Interferon-Beta improves survival in enterovirus-associated cardiomyopathy. Journal of the American College of Cardiology 2012 60 14 1295 1296 10.1016/j.jacc.2012.06.026
35. Hühn M. H., Hultcrantz M., Lind K., Ljunggren H. G., Malmberg K. J., Flodström-Tullberg M., IFN-gamma production dominates the early human natural killer cell response to Coxsackievirus infection. Cellular Microbiology 2008 10 2 426 436
36. Kanda T., Yokoyama T., Suzuki T., Murata K., Functional abnormalities of circulating natural killer cell subpopulations in patients with dilated cardiomyopathy. Tohoku Journal of Experimental Medicine 1992 168 3 529 537 2-s2.0-0026952072
37. Matsumori A., Molecular and immune mechanisms in the pathogenesis of cardiomyopathy-role of viruses, cytokines, and nitric oxide. Japanese Circulation Journal 1997 61 4 275 291 10.1253/jcj.61.275
38. Levine B., Kalman J., Mayer L., Fillit H. M., Packer M., Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. New England Journal of Medicine 1990 323 4 236 241 2-s2.0-0025286817
39. Mann D. L., Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circulation Research 2002 91 11 988 998 10.1161/01.RES.0000043825.01705.1B
40. Ishikawa C., Tsutamoto T., Fujii M., Sakai H., Tanaka T., Horie M., Prediction of mortality by high-sensitivity C-reactive protein and brain natriuretic peptide in patients with dilated cardiomyopathy. Circulation Journal 2006 70 7 857 863 2-s2.0-33745533241 10.1253/circj.70.857
41. Jarasch N., Martin U., Kamphausen E., Zell R., Wutzler P., Henke A., Interferon- γ -induced activation of nitric oxide-mediated antiviral activity of macrophages caused by a recombinant coxsackievirus B3. Viral Immunology 2005 18 2 355 364 2-s2.0-23344454604 10.1089/vim.2005.18.355
42. Lowenstein C. J., Hill S. L., Lafond-Walker A., Wu J., Allen G., Landavere M., Rose N. R., Herskowitz A., Nitric oxide inhibits viral replication in murine myocarditis. Journal of Clinical Investigation 1996 97 8 1837 1843 2-s2.0-0029996144
43. Shioi T., Matsumori A., Sasayama S., Persistent expression of cytokine in the chronic stage of viral myocarditis in mice. Circulation 1996 94 11 2930 2937 2-s2.0-0029797142
44. Gordon S., Martinez F. O., Alternative activation of macrophages: mechanism and functions. Immunity 2010 32 5 593 604 10.1016/j.immuni.2010.05.007
45. Banchereau J., Steinman R. M., Dendritic cells and the control of immunity. Nature 1998 392 6673 245 252 2-s2.0-0032546352 10.1038/32588
46. + dendritic cells define a protective phenotype in the mouse model of coxsackievirus myocarditis. Journal of Virology 2008 82 16 8149 8160 2-s2.0-49149119966 10.1128/JVI.00047-08
47. Rahnefeld A., Ebstein F., Albrecht N., Opitz E., Kuckelkorn U., Stangl K., Rehm A., Kloetzel P. M., Voigt A., Antigen-presentation capacity of dendritic cells is impaired in ongoing enterovirus myocarditis. European Journal of Immunology 2011 41 9 2774 2781 10.1002/eji.201041039
48. Leuschner F., Katus H. A., Kaya Z., Autoimmune myocarditis: past, present and future. Journal of Autoimmunity 2009 33 3-4 282 289 10.1016/j.jaut.2009.07. 009
49. Opavsky M. A., Penninger J., Aitken K., Wen W. H., Dawood F., Mak T., Liu P., Susceptibility to myocarditis is dependent on the response of α β T lymphocytes to coxsackieviral infection. Circulation Research 1999 85 6 551 558 2-s2.0-0033578663
50. Koehl B., Oualha M., Lesage F., Rambaud C., Canioni D., Hubert P., Leruez-Ville M., Fatal parvovirus B19 myocarditis in children and possible dysimmune mechanism. The Pediatric Infectious Disease Journal 2012 31 4 418 421 10.1097/INF.0b013e3182425786
51. Young L. H. Y., Joag S. V., Zheng L. M., Lee C. P., Lee Y. S., Young J. D. E., Perforin-mediated myocardial damage in acute myocarditis. The Lancet 1990 336 8722 1019 1021 2-s2.0-0025077187 10.1016/0140-6736(90)92486-2
52. Koga Y., Miyazaki Y., Toshima H., Hori Y., Takamoto T., Yokoyama M. M., Lymphocyte subsets in patients with acute myopericarditis, arrhythmias and dilated cardiomyopathy. Japanese Circulation Journal 1989 53 1 78 86 2-s2.0-0024523440
53. + T cells in peripheral blood of patients with dilated cardiomyopathy. Cellular Immunology 2010 263 2 224 229 10.1016/j.cellimm.2010.04.003
54. Gazzinelli R. T., Wysocka M., Hieny S., Scharton-Kersten T., Cheever A., Kühn R., Müller W., Trinchieri G., Sher A., In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN- γ and TNF- α Journal of Immunology 1996 157 2 798 805 2-s2.0-0029959459
55. Li Y., Heuser J. S., Kosanke S. D., Hemric M., Cunningham M. W., Protection against experimental autoimmune myocarditis is mediated by interleukin-10-producing T cells that are controlled by dendritic cells. American Journal of Pathology 2005 167 1 5 15 2-s2.0-21244441159
56. Gullestad L., Aass H., Fjeld J. G., Wikeby L., Andreassen A. K., Ihlen H., Simonsen S., Kjekshus J., Nitter-Hauge S., Ueland T., Lien E., Frøland S. S., Aukrust P., Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation 2001 103 2 220 225 2-s2.0-14344277564
57. Afanasyeva M., Wang Y., Kaya Z., Stafford E. A., Dohmen K. M., Sadighi Akha A. A., Rose N. R., Interleukin-12 receptor/STAT4 signaling is required for the development of autoimmune myocarditis in mice by an interferon- γ -independent pathway. Circulation 2001 104 25 3145 3151 2-s2.0-0035909925
58. Eriksson U., Kurrer M. O., Sebald W., Brombacher F., Kopf M., Dual role of the IL-12/IFN- γ axis in the development of autoimmune myocarditis: induction by IL-12 and protection by IFN- γ Journal of Immunology 2001 167 9 5464 5469 2-s2.0-0035500288
59. Wang Z., Hong J., Sun W., Xu G., Li N., Chen X., Liu A., Xu L., Sun B., Zhang J. Z., Role of IFN- γ in induction of Foxp3 and conversion of CD4+CD25- T cells to CD4+ Tregs. Journal of Clinical Investigation 2006 116 9 2434 2441 2-s2.0-33748294322 10.1172/JCI25826
60. Fairweather D., Frisancho-Kiss S., Yusung S. A., Barrett M. A., Davis S. E., Gatewood S. J. L., Njoku D. B., Rose N. R., Interferon- γ protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines transforming growth factor- β 1, interleukin-1 β and interleukin-4 in the heart. American Journal of Pathology 2004 165 6 1883 1894 2-s2.0-9644254471
61. Afanasyeva M., Georgakopoulos D., Belardi D. F., Bedja D., Fairweather D., Wang Y., Kaya Z., Gabrielson K. L., Rodriguez E. R., Caturegli P., Kass D. A., Rose N. R., Impaired up-regulation of CD25 on CD4+ T cells in IFN- γ knockout mice is associated with progression of myocarditis to heart failure. Proceedings of the National Academy of Sciences of the United States of America 2005 102 1 180 185 2-s2.0-19944427136 10.1073/pnas.0408241102
62. Huber K. C., Gersh B. J., Sugrue D. D., Frye R. L., Bailey K. R., Ritts R. E., T-lymphocyte subsets in patients with idiopathic dilated cardiomyopathy. International Journal of Cardiology 1989 22 1 59 66 2-s2.0-0024426862
63. McGeachy M. J., Cua D. J., Th17 cell differentiation: the long and winding road. Immunity 2008 28 4 445 453 2-s2.0-41549134361 10.1016/j.immuni. 2008.03.001
64. Solt L. A., Kumar N., Nuhant P., Wang Y., Lauer J. L., Liu J., Istrate M. A., Kamenecka T. M., Roush W. R., Vidović D., Schürer S. C., Xu J., Wagoner G., Drew P. D., Griffin P. R., Burris T. P., Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 2011 472 7344 491 494 10.1038/nature10075
65. Littman D. R., Rudensky A. Y., Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010 140 6 845 858 2-s2.0-77950349016 10.1016/j.cell.2010.02.021
66. Liu P. P., Mason J. W., Advances in the understanding of myocarditis. Circulation 2001 104 9 1076 1082 10.1161/hc3401.095198
67. Yi A., Jian L., Xiaojing H., Hui X., The prevalence of Th17 cells in patients with dilated cardiomyopathy. Clinical & Investigative Medicine 2009 32 2 E144 E150
68. Zee-Cheng C. S., Tsai C. C., Palmer D. C., Codd J. E., Pennington D. G., Williams G. A., High incidence of myocarditis by endomyocardial biopsy in patients with idiopathic congestive cardiomyopathy. Journal of the American College of Cardiology 1984 3 1 63 70 2-s2.0-0021334255
69. Caforio A. L. P., Goldman J. H., Baig M. K., Haven A. J., Dalla Libera L., Keeling P. J., McKenna W. J., Cardiac autoantibodies in dilated cardiomyopathy become undetectable with disease progression. Heart 1997 77 1 62 67 2-s2.0-0031046138
70. Klein R., Maisch B., Kochsiek K., Berg P. A., Demonstration of organ specific antibodies against heart mitochondria (anti-M7) in sera from patients with some forms of heart diseases. Clinical and Experimental Immunology 1984 58 2 283 292 2-s2.0-0021679117
71. Schultheiss H. P., Bolte H. D., Immunological analysis of auto-antibodies against the adenine nucleotide translocator in dilated cardiomyopathy. Journal of Molecular and Cellular Cardiology 1985 17 6 603 617 2-s2.0-0021876022
72. Fu L. X., Magnusson Y., Bergh C. H., Liljeqvist J. A., Waagstein F., Hjalmarson A., Hoebeke J., Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. Journal of Clinical Investigation 1993 91 5 1964 1968 2-s2.0-0027253970
73. Kaya Z., Katus H. A., Rose N. R., Cardiac troponins and autoimmunity: their role in the pathogenesis of myocarditis and of heart failure. Clinical Immunology 2010 134 1 80 88 2-s2.0-71649114492 10.1016/j.clim.2009.04.008
74. Rose N. R., Beisel K. W., Herskowitz A., Neu N., Wolfgram L. J., Alvarez F. L., Traystman M. D., Craig S. W., Cardiac myosin and autoimmune myocarditis. Ciba Foundation Symposium 1987 129 3 24 2-s2.0-0023506320
75. Limas C. J., Goldenberg I. F., Limas C., Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy. Circulation Research 1989 64 1 97 103 10.1161/01.RES.64.1.97
76. Magnusson Y., Wallukat G., Waagstein F., Hjalmarson A., Hoebeke J., Autoimmunity in idiopathic dilated cardiomyopathy: characterization of antibodies against the β 1-adrenoceptor with positive chronotropic effect. Circulation 1994 89 6 2760 2767 2-s2.0-0028225294
77. Kuhl U., Noutsias M., Seeberg B., Schultheiss H. P., Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart 1996 75 3 295 300 2-s2.0-0029883588
78. Kühl U., Schultheiss H. P., Myocarditis: early biopsy allows for tailored regenerative treatment. Deutsches Ärzteblatt International 2012 109 20 361 368
79. Friedenstein A. J., Chailakhjan R. K., Lalykina K. S., The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell and Tissue Kinetics 1970 3 4 393 403 2-s2.0-0014855869
80. Pittenger M. F., Mackay A. M., Beck S. C., Jaiswal R. K., Douglas R., Mosca J. D., Moorman M. A., Simonetti D. W., Craig S., Marshak D. R., Multilineage potential of adult human mesenchymal stem cells. Science 1999 284 5411 143 147 2-s2.0-0033515827 10.1126/science.284.5411.143
81. Fraser J. K., Wulur I., Alfonso Z., Hedrick M. H., Fat tissue: an underappreciated source of stem cells for biotechnology. Trends in Biotechnology 2006 24 4 150 154 2-s2.0-33646103658 10.1016/j.tibtech.2006.01.010
82. Cao C., Dong Y., Dong Y., Study on culture and in vitro osteogenesis of blood-derived human mesenchymal stem cells. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2005 19 8 642 647 2-s2.0-33846009544
83. Griffiths M. J. D., Bonnet D., Janes S. M., Stem cells of the alveolar epithelium. The Lancet 2005 366 9481 249 260 2-s2.0-22144481028 10.1016/S0140-6736(05)66916-4
84. Beltrami A. P., Barlucchi L., Torella D., Baker M., Limana F., Chimenti S., Kasahara H., Rota M., Musso E., Urbanek K., Leri A., Kajstura J., Nadal-Ginard B., Anversa P., Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003 114 6 763 776 2-s2.0-10744228523 10.1016/S0092-8674(03)00687-1
85. Haag M., van Linthout S., Schröder S. E. A., Freymann U., Ringe J., Tschöpe C., Sittinger M., Endomyocardial biopsy derived adherent proliferating cells-a potential cell source for cardiac tissue engineering. Journal of Cellular Biochemistry 2010 109 3 564 575
86. Miteva K., Haag M., Peng J., Savvatis K., Becher P. M., Seifert M., Warstat K., Westermann D., Ringe J., Sittinger M., Schultheiss H. P., Tschöpe C., van Linthout S., Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis. PLoS ONE 2011 6 12, article e28513
87. Haag M., Stolk M., Ringe J., Linthout S. V., Tschöpe C., Sittinger M., Seifert M., Immune attributes of cardiac-derived adherent proliferating (CAP) cells in cardiac therapy. Journal of Tissue Engineering and Regenerative Medicine 2012 7 5 362 370 10.1002/term.531
88. Bachmann M. F., Kopf M., On the role of the innate immunity in autoimmune disease. The Journal of Experimental Medicine 2001 193 12 f47 f50 10.1084/jem.193.12.F47
89. Kaya Z., Afanasyeva M., Wang Y., Dohmen K. M., Schlichting J., Tretter T., Fairweather D., Holers V. M., Rose N. R., Contribution of the innate immune system to autoimmune myocarditis: a role for complement. Nature Immunology 2001 2 8 739 745 2-s2.0-0034891226 10.1038/90686
90. Soehnlein O., Lindbom L., Phagocyte partnership during the onset and resolution of inflammation. Nature Reviews Immunology 2010 10 6 427 439 10.1038/nri2779
91. Medzhitov R., Inflammation 2010: new adventures of an old flame. Cell 2010 140 6 771 776 2-s2.0-77950345093 10.1016/j.cell.2010.03.006
92. Mosser D. M., Edwards J. P., Exploring the full spectrum of macrophage activation. Nature Reviews Immunology 2008 8 12 958 969 10.1038/nri2448
93. Kim J., Hematti P., Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Experimental Hematology 2009 37 12 1445 1453 10.1016/j.exphem.2009.09.004
94. François M., Romieu-Mourez R., Li M., Galipeau J., Human MSC suppression correlates with cytokine induction of indoleamine 2, 3-dioxygenase and bystander M2 macrophage differentiation. Molecular Therapy 2012 20 1 187 195 10.1038/mt.2011.189
95. Németh K., Leelahavanichkul A., Yuen P. S. T., Mayer B., Parmelee A., Doi K., Robey P. G., Leelahavanichkul K., Koller B. H., Brown J. M., Hu X., Jelinek I., Star R. A., Mezey É.., Bone marrow stromal cells attenuate sepsis via prostaglandin E 2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nature Medicine 2009 15 1 42 49 2-s2.0-58149326737 10.1038/nm.1905
96. Maggini J., Mirkin G., Bognanni I., Holmberg J., Piazzón I. M., Nepomnaschy I., Costa H., Cañones C., Raiden S., Vermeulen M., Geffner J. R., Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS ONE 2010 5 2, article e9252 2-s2.0-77949537626 10.1371/journal.pone.0009252
97. Mougiakakos D., Jitschin R., Johansson C. C., Okita R., Kiessling R., Le Blanc K., The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood 2011 117 18 4826 4835 2-s2.0-79955971620 10.1182/blood-2010-12-324038
98. Choi H., Lee R. H., Bazhanov N., Oh J. Y., Prockop D. J., Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF- B signaling in resident macrophages. Blood 2011 118 2 330 338 2-s2.0-79960464308 10.1182/blood-2010-12- 327353
99. Ortiz L. A., DuTreil M., Fattman C., Pandey A. C., Torres G., Go K., Phinney D. G., Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proceedings of the National Academy of Sciences of the United States of America 2007 104 26 11002 11007 2-s2.0-34547402979 10.1073/pnas.0704421104
100. Hühn M. H., Hultcrantz M., Lind K., Ljunggren H. G., Malmberg K. J., Flodström-Tullberg M., IFN- γ production dominates the early human natural killer cell response to Coxsackievirus infection. Cellular Microbiology 2008 10 2 426 436 2-s2.0-38049134286 10.1111/j.1462-5822.2007.01056.x
101. Spaggiari G. M., Capobianco A., Abdelrazik H., Becchetti F., Mingari M. C., Moretta L., Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008 111 3 1327 1333 2-s2.0-38949183675 10.1182/blood-2007-02-074997
102. Rasmusson I., Ringdén O., Sundberg B., Le Blanc K., Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003 76 8 1208 1213 2-s2.0-0242300602 10.1097/01.TP.0000082540.43730.80
103. Poggi A., Prevosto C., Massaro A. M., Negrini S., Urbani S., Pierri I., Saccardi R., Gobbi M., Zocchi M. R., Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors. Journal of Immunology 2005 175 10 6352 6360 2-s2.0-27744541175
104. Spaggiari G. M., Capobianco A., Becchetti S., Mingari M. C., Moretta L., Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood 2006 107 4 1484 1490 2-s2.0-32644438233 10.1182/blood-2005-07-2775
105. Patel S. A., Meyer J. R., Greco S. J., Corcoran K. E., Bryan M., Rameshwar P., Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF- β Journal of Immunology 2010 184 10 5885 5894 2-s2.0-77954728855 10.4049/jimmunol.0903143
106. Sotiropoulou P. A., Perez S. A., Gritzapis A. D., Baxevanis C. N., Papamichail M., Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006 24 1 74 85 2-s2.0-33645508766 10.1634/stemcells. 2004-0359
107. Aggarwal S., Pittenger M. F., Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005 105 4 1815 1822 2-s2.0-13544249606 10.1182/blood-2004-04-1559
108. Yuan J., Liu Z., Lim T., Zhang H., He J., Walker E., Shier C., Wang Y., Su Y., Sall A., McManus B., Yang D., CXCL10 inhibits viral replication through recruitment of natural killer cells in coxsackievirus B3-induced myocarditis. Circulation Research 2009 104 5 628 638 10.1161/CIRCRESAHA.108.192179
109. Daniela Cihakova S. O., Natural killer cells suppress cardiac eosinophilia in autoimmune myocarditis. The Journal of Immunology 2012 188 article 171. 21
110. Koike H., Kanda T., Sumino H., Yokoyama T., Arai M., Motooka M., Suzuki T., Tamura J., Kobayashi I., Reduction of viral myocarditis in mice lacking perforin. Research Communications in Molecular Pathology and Pharmacology 2001 110 3-4 229 237 2-s2.0-0037623371
111. Chen L., Zhang W., Yue H., Han Q., Chen B., Shi M., Li J., Li B., You S., Shi Y., Zhao R. C., Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells. Stem Cells and Development 2007 16 5 719 731 2-s2.0-36248968773 10.1089/scd.2007.0065
112. Jiang Z. J., Xu W., Li K., Yue Y., Xu L., Ye F., Xiong S., Remission of CVB3-induced viral myocarditis by in vivo Th2 polarization via hydrodynamics-based interleukin-4 gene transfer. Journal of Gene Medicine 2008 10 8 918 929 2-s2.0-49349101920 10.1002/jgm.1215
113. Abston E. D., Coronado M. J., Bucek A., Bedja D., Shin J., Kim J. B., Kim E., Gabrielson K. L., Georgakopoulos D., Mitzner W., Fairweather D., Th2 regulation of viral myocarditis in mice: different roles for TLR3 versus TRIF in progression to chronic disease. Clinical and Developmental Immunology 2012 2012 12 129486 10.1155/2012/129486
114. Zhang W., Ge W., Li C., You S., Liao L., Han Q., Deng W., Zhao R. C. H., Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells and Development 2004 13 3 263 271 2-s2.0-2942562525 10.1089/154732804323099190
115. Ramasamy R., Fazekasova H., Lam E. W. F., Soeiro I., Lombardi G., Dazzi F., Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation 2007 83 1 71 76 2-s2.0-33846220680 10.1097/01.tp.0000244572.24780.54
116. Maccario R., Podestà M., Moretta A., Cometa A., Comoli P., Montagna D., Daudt L., Ibatici A., Piaggio G., Pozzi S., Frassoni F., Locatelli F., Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005 90 4 516 525 2-s2.0-17844391825
117. Chiesa S., Morbelli S., Morando S., Massollo M., Marini C., Bertoni A., Frassoni F., Bartolomé S. T., Sambuceti G., Traggiai E., Uccelli A., Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 2011 108 42 17384 17389 10.1073/pnas.1103650108
118. Ahuja S. S., Estrada C. A., Lindsey M. L., Crosstalk between cytotoxic T-lymphocyte-associated antigen-4 and interleukin-12 in cytotoxic T-lymphocyte-mediated myocarditis: adding another link to the chain. Circulation Research 2007 101 3 218 220 2-s2.0-34548319713 10.1161/CIRCRESAHA.107.158238
119. Bartholomew A., Sturgeon C., Siatskas M., Ferrer K., McIntosh K., Patil S., Hardy W., Devine S., Ucker D., Deans R., Moseley A., Hoffman R., Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Experimental Hematology 2002 30 1 42 48 2-s2.0-0036142769 10.1016/S0301-472X(01)00769-X
120. Tse W. T., Pendleton J. D., Beyer W. M., Egalka M. C., Guinan E. C., Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003 75 3 389 397 2-s2.0-0037442264 10.1097/01.TP.0000045055.63901.A9
121. 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 12 4619 4621 2-s2.0-2942595706 10.1182/blood-2003-11-3909
122. Zappia E., Casazza S., Pedemonte E., Benvenuto F., Bonanni I., Gerdoni E., Giunti D., Ceravolo A., Cazzanti F., Frassoni F., Mancardi G., Uccelli A., Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 2005 106 5 1755 1761 2-s2.0-23944519424 10.1182/blood-2005-04-1496
123. Rasmusson I., Ringdén O., Sundberg B., Le Blanc K., Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Experimental Cell Research 2005 305 1 33 41 2-s2.0-15044348816 10.1016/j.yexcr.2004.12.013
124. Krampera M., Glennie S., Dyson J., Scott D., Laylor R., Simpson E., Dazzi F., Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003 101 9 3722 3729 2-s2.0-0038204193 10.1182/blood-2002-07-2104
125. Glennie S., Soeiro I., Dyson P. J., Lam E. W. F., Dazzi F., Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005 105 7 2821 2827 2-s2.0-15944376184 10.1182/blood-2004-09-3696
126. Akiyama K., Chen C., Wang D., Xu X., Qu C., Yamaza T., Cai T., Chen W., Sun L., Shi S., Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 2012 10 5 544 555 10.1016/j.stem.2012.03.007
127. Savvatis K., van Linthout S., Miteva K., Pappritz K., Westermann D., Schefold J. C., Fusch G., Weithäuser A., Rauch U., Becher P. M., Klingel K., Ringe J., Kurtz A., Schultheiss H. P., Tschöpe C., Mesenchymal stromal cells but not cardiac fibroblasts exert beneficial systemic immunomodulatory effects in experimental myocarditis. PLoS ONE 2012 7 7, article e41047
128. Bouffi C., Bony C., Courties G., Jorgensen C., Noël D., IL-6-dependent PGE2 secretion by mesenchymal stem cells inhibits local inflammation in experimental arthritis. PLoS ONE 2010 5 12, article e14247 2-s2.0-78650085746 10.1371/journal.pone.0014247
129. Kong Q. F., Sun B., Bai S. S., Zhai D. X., Wang G. Y., Liu Y. M., Zhang S. J., Li R., Zhao W., Sun Y. Y., Li N., Wang Q., Peng H. S., Jin L. H., Li H. L., Administration of bone marrow stromal cells ameliorates experimental autoimmune myasthenia gravis by altering the balance of Th1/Th2/Th17/Treg cell subsets through the secretion of TGF- β Journal of Neuroimmunology 2009 207 1-2 83 91 2-s2.0-60149097402 10.1016/j.jneuroim.2008.12.005
130. Zhao W., Wang Y., Wang D., Sun B., Wang G., Wang J., Kong Q., Wang Q., Peng H., Jin L., Li H., TGF- β expression by allogeneic bone marrow stromal cells ameliorates diabetes in NOD mice through modulating the distribution of CD4+ T cell subsets. Cellular Immunology 2008 253 1-2 23 30 2-s2.0-51449109360 10.1016/j.cellimm.2008.06.009
131. Henke A., Zell R., Martin U., Stelzner A., Direct interferon- γ -mediated protection caused by a recombinant coxsackievirus B3. Virology 2003 315 2 335 344 2-s2.0-0142185270 10.1016/S0042-6822(03)00538-5
132. Levings M. K., Bacchetta R., Schulz U., Roncarolo M. G., The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. International Archives of Allergy and Immunology 2002 129 4 263 276 2-s2.0-0036886390
133. Wood K. J., Sawitzki B., Interferon gamma: a crucial role in the function of induced regulatory T cells in vivo. Trends in Immunology 2006 27 4 183 187 10.1016/j.it.2006.02.008
134. Bai L., Lennon D. P., Eaton V., Maier K., Caplan A. I., Miller S. D., Miller R. H., Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 2009 57 11 1192 1203 10.1002/glia.20841
135. 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. Journal of Immunology 2010 185 1 302 312 2-s2.0-77956215701 10.4049/jimmunol.0902007
136. Duffy M. M., Pindjakova J., Hanley S. A., McCarthy C., Weidhofer G. A., Sweeney E. M., English K., Shaw G., Murphy J. M., Barry F. P., Mahon B. P., Belton O., Ceredig R., Griffin M. D., 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. European Journal of Immunology 2011 41 10 2840 2851 10.1002/eji.201141499
137. Casiraghi F., Azzollini N., Cassis P., Imberti B., Morigi M., Cugini D., Cavinato R. A., Todeschini M., Solini S., Sonzogni A., Perico N., Remuzzi G., Noris M., Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. Journal of Immunology 2008 181 6 3933 3946 2-s2.0-56149110595
138. Wang Y., Zhang A., Ye Z., Xie H., Zheng S., Bone marrow-derived mesenchymal stem cells inhibit acute rejection of rat liver allografts in association with regulatory T-cell expansion. Transplantation Proceedings 2009 41 10 4352 4356 2-s2.0-71549118838 10.1016/j.transproceed.2009.08.072
139. Ge W., Jiang J., Baroja M. L., Arp J., Zassoko R., Liu W., Bartholomew A., Garcia B., Wang H., Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. American Journal of Transplantation 2009 9 8 1760 1772 2-s2.0-67650932291 10.1111/j.1600-6143.2009.02721.x
140. Kavanagh H., Mahon B. P., Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 2011 66 4 523 531 2-s2.0-79952042164 10.1111/j.1398-9995.2010.02509.x
141. Rafei M., Campeau P. M., Aguilar-Mahecha A., Buchanan M., Williams P., Birman E., Yuan S., Young Y. K., Boivin M. N., Forner K., Basik M., Galipeau J., Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner. Journal of Immunology 2009 182 10 5994 6002 2-s2.0-70349881103 10.4049/jimmunol.0803962
142. Selmani Z., Naji A., Zidi I., Favier B., Gaiffe E., Obert L., Borg C., Saas P., Tiberghien P., Rouas-Freiss N., Carosella E. D., Deschaseaux F., 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 1 212 222 2-s2.0-38349053355 10.1634/stemcells.2007-0554
143. English K., Ryan J. M., Tobin L., Murphy M. J., Barry F. P., Mahon B. P., 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. Clinical and Experimental Immunology 2009 156 1 149 160 2-s2.0-61849123247 10.1111/j.1365-2249.2009.03874. x
144. Ge W., Jiang J., Arp J., Liu W., Garcia B., Wang H., Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation 2010 90 12 1312 1320 2-s2.0-78650827566 10.1097/TP.0b013e3181fed001
145. Popp F. C., Eggenhofer E., Renner P., Slowik P., Lang S. A., Kaspar H., Geissler E. K., Piso P., Schlitt H. J., Dahlke M. H., Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate. Transplant Immunology 2008 20 1-2 55 60 2-s2.0-56049100237 10.1016/j.trim.2008.08.004
146. Madec A. M., Mallone R., Afonso G., Abou Mrad E., Mesnier A., Eljaafari A., Thivolet C., Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells. Diabetologia 2009 52 7 1391 1399 2-s2.0-67349224622 10.1007/s00125-009-1374-z
147. Zhang Q., Shi S., Liu Y., Uyanne J., Shi Y., Shi S., Le A. D., Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. Journal of Immunology 2009 183 12 7787 7798 2-s2.0-76249084930 10.4049/jimmunol.0902318
148. Nemeth K., Keane-Myers A., Brown J. M., Metcalfe D. D., Gorham J. D., Gorham J. D., Bundoc V. G., Bundoc V. G., Hodges M. G., Jelinek I., Madala S., Karpati S., Mezey E., Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proceedings of the National Academy of Sciences of the United States of America 2010 107 12 5652 5657 10.1073/pnas.0910720107
149. Sheng H., Wang Y., Jin Y., Zhang Q., Zhang Y., Wang L., Shen B., Yin S., Liu W., Cui L., Li N., A critical role of IFN γ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell Research 2008 18 8 846 857 2-s2.0-49149120713 10.1038/cr.2008.80
150. Krampera M., Cosmi L., Angeli R., Pasini A., Liotta F., Andreini A., Santarlasci V., Mazzinghi B., Pizzolo G., Vinante F., Romagnani P., Maggi E., Romagnani S., Annunziato F., Role for interferon- γ in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006 24 2 386 398 2-s2.0-33746889097 10.1634/stemcells.2005-0008
151. Ryan J. M., Barry F., Murphy J. M., Mahon B. P., Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clinical & Experimental Immunology 2007 149 2 353 363 10.1111/j.1365-2249.2007.03422.x
152. Nicola M. D., Carlo-Stella C., Magni M., Milanesi M., Longoni P. D., Matteucci P., Grisanti S., Gianni A. M., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002 99 10 3838 3843 2-s2.0-0037093058 10.1182/blood.V99.10.3838
153. Chabannes D., Hill M., Merieau E., Rossignol J., Brion R., Soulillou J. P., Anegon I., Cuturi M. C., A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 2007 110 10 3691 3694 2-s2.0-36349017810 10.1182/blood-2007-02-075481
154. Morandi F., Raffaghello L., Bianchi G., Meloni F., Salis A., Millo E., Ferrone S., Barnaba V., Pistoia V., Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens. Stem Cells 2008 26 5 1275 1287 2-s2.0-47949099102 10.1634/stemcells.2007-0878
155. Lee R. H., Pulin A. A., Seo M. J., Kota D. J., Ylostalo J., Larson B. L., Semprun-Prieto L., Delafontaine P., Prockop D. J., 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 2-s2.0-67649171661 10.1016/j.stem.2009.05.003
156. Mitchison N. A., Wedderburn L. R., B cells in autoimmunity. Proceedings of the National Academy of Sciences of the United States of America 2000 97 16 8750 8751 10.1073/pnas.97.16.8750
157. Krebs P., Kurrer M. O., Kremer M., De Giuli R., Sonderegger I., Henke A., Maier R., Ludewig B., Molecular mapping of autoimmune B cell responses in experimental myocarditis. Journal of Autoimmunity 2007 28 4 224 233 2-s2.0-34248576416 10.1016/j.jaut.2007.01.003
158. Mauri C., Bosma A., Immune regulatory function of B cells. Annual Review of Immunology 2012 30 221 241 10.1146/annurev-immunol-020711-074934
159. Carter N. A., Vasconcellos R., Rosser E. C., Tulone C., Muñoz-Suano A., Kamanaka M., Ehrenstein M. R., Flavell R. A., Mauri C., Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. Journal of Immunology 2011 186 10 5569 5579 2-s2.0-79956224216 10.4049/jimmunol.1100284
160. Che N., Li X., Zhou S., Liu R., Shi D., Lu L., Sun L., Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation. Cellular Immunology 2012 274 1-2 46 53 10.1016/j.cellimm.2012.02.004
161. Asari S., Itakura S., Ferreri K., Liu C. P., Kuroda Y., Kandeel F., Mullen Y., Mesenchymal stem cells suppress B-cell terminal differentiation. Experimental Hematology 2009 37 5 604 615 2-s2.0-64249129065 10.1016/j.exphem.2009.01.005
162. Corcione A., Benvenuto F., Ferretti E., Giunti D., Cappiello V., Cazzanti F., Risso M., Gualandi F., Mancardi G. L., Pistoia V., Uccelli A., Human mesenchymal stem cells modulate B-cell functions. Blood 2006 107 1 367 372 2-s2.0-30144440925 10.1182/blood-2005-07-2657
163. Ren G., Zhang L., Zhao X., Xu G., Zhang Y., Roberts A. I., Zhao R. C., Shi Y., Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008 2 2 141 150 2-s2.0-38649105374 10.1016/j.stem.2007.11.014
164. Ren G., Su J., Zhang L., Zhao X., Ling W., 'huillie A. L., Zhang J., Lu Y., Roberts A. I., Ji W., Zhang H., Rabson A. B., Shi Y., Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells 2009 27 8 1954 1962 10.1002/stem.118
165. van den Berk L. C. J., Jansen B. J. H., Siebers-Vermeulen K. G. C., Netea M. G., Latuhihin T., Bergevoet S., Raymakers R. A., Kögler G., Figdor C. C., Adema G. J., Torensma R., Toll-like receptor triggering in cord blood mesenchymal stem cells. Journal of Cellular and Molecular Medicine 2009 13 9 3415 3426 10.1111/j.1582-4934.2008.00653.x
166. Delarosa O., Lombardo E., Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeutic potential. Mediators of Inflammation 2010 2010 2-s2.0-77954551154 10.1155/2010/865601 865601
167. Kim H. S., Shin T. H., Yang S. R., Seo M. S., Kim D. J., Kang S. K., Park J. H., Kang K. S., Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood. PLoS ONE 2010 5 10, article e15369 2-s2.0-78149452823 10.1371/journal.pone.0015369
168. Raicevic G., Najar M., Stamatopoulos B., de Bruyn C., Meuleman N., Bron D., Toungouz M., Lagneaux L., The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties. Cellular Immunology 2011 270 2 207 216 10.1016/j.cellimm.2011.05.010
169. Tomic S., Djokic J., Vasilijic S., Vucevic D., Todorovic V., Supic G., Colic M., Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by Toll-like receptor agonists. Stem Cells and Development 2011 20 4 695 708 10.1089/scd.2010.0145
170. Raicevic G., Rouas R., Najar M., Stordeur P., Id Boufker H., Bron D., Martiat P., Goldman M., Nevessignsky M. T., Lagneaux L., Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells. Human Immunology 2010 71 3 235 244 2-s2.0-76949094176 10.1016/j.humimm.2009.12.005
171. Opitz C. A., Litzenburger U. M., Lutz C., Lanz T. V., Tritschler I., Köppel A., Tolosa E., Hoberg M., Anderl J., Aicher W. K., Weller M., Wick W., Platten M., 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 4 909 919 10.1002/stem.7
172. Sioud M., Mobergslien A., Boudabous A., Fløisand Y., Evidence for the involvement of galectin-3 in mesenchymal stem cell suppression of allogeneic T-cell proliferation. Scandinavian Journal of Immunology 2010 71 4 267 274 2-s2.0-77949985881 10.1111/j.1365-3083.2010.02378.x
173. Liotta F., Angeli R., Cosmi L., Filì L., Manuelli C., Frosali F., Mazzinghi B., Maggi L., Pasini A., Lisi V., Santarlasci V., Consoloni L., Angelotti M. L., Romagnani P., Parronchi P., Krampera M., Maggi E., Romagnani S., Annunziato F., Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing notch signaling. Stem Cells 2008 26 1 279 289 2-s2.0-38349060182 10.1634/stemcells.2007-0454
174. Romieu-Mourez R., François M., Boivin M. N., Bouchentouf M., Spaner D. E., Galipeau J., Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype. Journal of Immunology 2009 182 12 7963 7973 2-s2.0-67649209791 10.4049/jimmunol.0803864
175. Waterman R. S., Tomchuck S. L., Henkle S. L., Betancourt A. M., A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS ONE 2010 5 4, article e10088 2-s2.0-77956420421 10.1371/journal.pone.0010088
176. Freyman T., Polin G., Osman H., Crary J., Lu M., Cheng L., Palasis M., Wilensky R. L., A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. European Heart Journal 2006 27 9 1114 1122 2-s2.0-33646269967 10.1093/eurheartj/ehi818
177. Roddy G. W., Oh J. Y., Lee R. H., Bartosh T. J., Ylostalo J., Coble K., Rosa R. H. Jr., Prockop D. J., Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF- α stimulated gene/protein 6. Stem Cells 2011 29 10 1572 1579 10.1002/stem.708
178. Shen Y., Xu W., Chu Y. W., Wang Y., Liu Q. S., Xiong S. D., Coxsackievirus group B type 3 infection upregulates expression of monocyte chemoattractant protein 1 in cardiac myocytes, which leads to enhanced migration of mononuclear cells in viral myocarditis. Journal of Virology 2004 78 22 12548 12556 2-s2.0-7644244579 10.1128/JVI.78.22.12548-12556.2004
179. Leuschner F., Panizzi P., Chico-Calero I., Lee W. W., Ueno T., Cortez-Retamozo V., Waterman P., Gorbatov R., Marinelli B., Iwamoto Y., Chudnovskiy A., Figueiredo J. L., Sosnovik D. E., Pittet M. J., Swirski F. K., Weissleder R., Nahrendorf M., Angiotensin-converting enzyme inhibition prevents the release of monocytes from their splenic reservoir in mice with myocardial infarction. Circulation Research 2010 107 11 1364 1373 10.1161/CIRCRESAHA.110. 227454
180. Kishimoto C., Abelmann W. H., Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice. Circulation 1989 79 6 1300 1308 2-s2.0-0024354923
181. Belema-Bedada F., Uchida S., Martire A., Kostin S., Braun T., Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Cell Stem Cell 2008 2 6 566 575 2-s2.0-44349088779 10.1016/j.stem.2008.03.003
182. Escher F., Schmidt-Lucke C., van Linthout S., Savvatis K., Schultheiss H.-P., Tschöpe C., Cardiac migration of mesenchymal stem cells in patients with inflammatory cardiomyopathy. European Heart Journal 2010 31 464 465 10.1093/eurheartj/ehp479
183. Fox J. M., Chamberlain G., Ashton B. A., Middleton J., Recent advances into the understanding of mesenchymal stem cell trafficking. British Journal of Haematology 2007 137 6 491 502 2-s2.0-34249290744 10.1111/j.1365-2141.2007. 06610.x
184. Wu G. D., Nolta J. A., Jin Y. S., Barr M. L., Yu H., Starnes V. A., Cramer D. V., Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation 2003 75 5 679 685 2-s2.0-0037443911 10.1097/01.TP.0000048488.35010.95
185. Horwitz E. M., Gordon P. L., Koo W. K. K., Marx J. C., Neel M. D., McNall R. Y., Muul L., Hofmann T., Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proceedings of the National Academy of Sciences of the United States of America 2002 99 13 8932 8937 2-s2.0-0037173116 10.1073/pnas.132252399
186. Wang Y., Han Z. B., Ma J., Zuo C., Geng J., Gong W., Sun Y., Li H., Wang B., Zhang L., He Y., Chao Han Z., A toxicity study of multipleadministration human umbilical cord mesenchymal stem cells in cynomolgus monkeys. Stem Cells and Development 2012 21 9 1401 1408 10.1089/scd.2011.0441
187. van Linthout S., Savvatis K., Miteva K., Peng J., Ringe J., Warstat K., Schmidt-Lucke C., Sittinger M., Schultheiss H. P., Tschöpe C., Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis. European Heart Journal 2011 32 17 2168 2178 10.1093/eurheartj/ehq467
188. Schultheiss H. P., Kühl U., Cooper L. T., The management of myocarditis. European Heart Journal 2011 32 21 2616 2625 10.1093/eurheartj/ ehr165