Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: Implications for cellular-based therapy

Clinical and Experimental Immunology

Volumn 173, Issue 2, 2013, Pages 195-206

  Cipriani, P ^a   Di Benedetto, P ^a   Liakouli, V ^a   Del Papa, B ^b   Di Padova, M ^b   Di Ianni, M ^c   Marrelli, A ^a   Alesse, E ^b   Giacomelli, R ^a  

^a Chair and Clinical Unit of Rheumatology   (Italy)

^b UNIVERSITY OF L'AQUILA   (Italy)

^c UNIVERSITY OF PERUGIA   (Italy)

Author keywords

immunomodulatory abilities; mesenchymal stem cells; senescence; systemic sclerosis

Indexed keywords

ANTINUCLEAR ANTIBODY; BETA GALACTOSIDASE; BIOLOGICAL MARKER; CD69 ANTIGEN; CENTROMERE ANTIBODY; DEXAMETHASONE; DOXORUBICIN; INTERLEUKIN 6; PROTEIN P21; PROTEIN P53; SCL 70 ANTIBODY; TRANSFORMING GROWTH FACTOR BETA;

ADAPTIVE IMMUNITY; ADIPOGENESIS; ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CELL CYCLE; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL DIFFERENTIATION; CELL FUNCTION; CELL ISOLATION; CELL PROLIFERATION; CELL THERAPY; CLINICAL ARTICLE; COCULTURE; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENZYME ACTIVITY; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE PROLIFERATION; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MIXED LYMPHOCYTE REACTION; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY T LYMPHOCYTE; SENESCENCE; SYSTEMIC SCLEROSIS; T LYMPHOCYTE; WESTERN BLOTTING;

IMMUNOMODULATORY ABILITIES; MESENCHYMAL STEM CELLS; SENESCENCE; SYSTEMIC SCLEROSIS;

ANTIGENS, CD; ANTIGENS, DIFFERENTIATION, T-LYMPHOCYTE; BETA-GALACTOSIDASE; CELL AGING; CELL PROLIFERATION; CELL- AND TISSUE-BASED THERAPY; CELLS, CULTURED; COCULTURE TECHNIQUES; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DOXORUBICIN; HUMANS; IMMUNOMODULATION; INTERLEUKIN-6; LECTINS, C-TYPE; MESENCHYMAL STROMAL CELLS; SCLERODERMA, SYSTEMIC; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84880032316     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/cei.12111     Document Type: Article

References (61)

1. Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol 2009; 217:318-324.
2. Pittenger MF, Mackay AM, Beck SC etal. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143-147.
3. Le Blanc K, Frassoni F, Ball L etal. Developmental Committee of the European Group for Blood and Marrow transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a Phase II study. Lancet 2008; 371:1579-1586.
4. Dominici M, Le Blanc K, Mueller I etal. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315-317.
5. Oswald J, Boxberger S, Jørgensen B etal. Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 2004; 22:377-384.
6. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105:1815-1822.
7. Yi T, Song SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharm Res 2012; 35:213-221.
8. Jiang X, Zhang Y, Liu B etal. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005; 105:4120-4126.
9. Shi M, Liu ZW, Wang FS. Immunomodulatory properties and therapeutic application of mesenchymal stem cells. Clin Exp Immunol 2011; 164:1-8.
10. Burr SP, Dazzi F, Garden OA. Mesenchymal stromal cells and regulatory T cells: the Yin and Yang of peripheral tolerance? Immunol Cell Biol 2013; 91:12-18.
11. Prevosto C, Zancolli M, Canevali P etal. Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 2007; 92:881-888.
12. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007; 110:3499-3506.
13. Long SA, Buckner JH. CD4+FOXP3+ T regulatory cells in human autoimmunity: more than a numbers game. J Immunol 2011; 187:2061-2066.
14. Cipriani P, Fulminis A, Pingiotti E etal. Resistance to apoptosis in circulating alpha/beta and gamma/delta T lymphocytes from patients with systemic sclerosis. J Rheumatol 2006; 33:2003-2014.
15. Bosello S, De Luca G, Tolusso B etal. B cells in systemic sclerosis: a possible target for therapy. Autoimmun Rev 2011; 10:624-630.
16. van Lieshout AW, Vonk MC, Bredie SJ etal. Enhanced interleukin-10 production by dendritic cells upon stimulation with Toll-like receptor 4 agonists in systemic sclerosis that is possibly implicated in CCL18 secretion. Scand J Rheumatol 2009; 38:282-290.
17. Cipriani P, Guiducci S, Miniati I etal. Impaired endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into pathogenesis of systemic sclerosis. Arthritis Rheum 2007; 56:1994-2004.
18. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005; 120:513-522.
19. Larghero J, Farge D, Braccini A etal. Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cells from patients with systemic sclerosis. Ann Rheum Dis 2008; 67:443-449.
20. + regulatory T cells. Clin Exp Immunol 2009; 156:149-160.
21. De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A etal. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012; 12:574-591.
22. Di Nicola M, Carlo-Stella C, Magni M etal. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 15:3838-3843.
23. Deuse T, Stubbendorff M, Tang-Quan K etal. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant 2011; 20:655-667.
24. Nemeth K, Keane-Myers A, Brown JM etal. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci USA 2010; 107:5652-5657.
25. Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev 2010; 10:319-329.
26. Djouad F, Charbonnier LM, Bouffi C etal. Mesenchymal stem cells inhibit the differentiation of dendritic cells through aninterleukin-6-dependent mechanism. Stem Cells 2007; 25:2025-2032.
27. Radstake TRDJ, van Bon L, Broen J etal. Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFβ expression. PloS One 2009; 6:e5981-5992.
28. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000; 182:311-322.
29. Buttiglieri S, Ruella M, Risso A etal. The aging effect of chemotherapy on cultured human mesenchymal stem cells. Exp Hematol 2011; 39:1171-1181.
30. Landgraf K, Brunauer R, Lepperdinger G etal. The suppressive effect of mesenchymal stromal cells on T cell proliferation is conserved in old age. Transpl Immunol 2011; 25:167-172.
31. Quaedackers ME, Baan C, Weimar W etal. Cell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytes. Eur J Immunol 2009; 39:3436-3446.
32. Akiyama K, Chen C, Wang D etal. Mesenchymal-stem-cell induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 2012; 10:544-545.
33. Kong QF, Sun B, Bai SS etal. 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 TGFbeta. J Neuroimmunol 2009; 207:83-91.
34. Ghannam S, Pene J, Torcy-Moquet G etal. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol 2010; 185:302-312.
35. Rafei M, Campeau PM, Aguilar-Mahecha A etal. Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner. J Immunol 2009; 182:5994-6002.
36. Goodman WA, Cooper KD, McCormick TS. Regulation generation: the suppressive functions of human regulatory T cells. Crit Rev Immunol 2012; 32:65-79.
37. Wright GP, Stauss HJ, Ehrenstein MR. Therapeutic potential of Tregs to treat rheumatoid arthritis. Semin Immunol 2011; 23:195-201.
38. Iikuni N, Lourenço EV, Hahn BH etal. Regulatory T cells directly suppress B cells in systemic lupus erythematosus. J Immunol 2009; 183:1518-1522.
39. Brusko TM, Putnam AL, Bluestone JA. Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol Rev 2008; 223:371-390.
40. Hess AD. Modulation of graft-versus-host disease: role of regulatory T lymphocytes. Biol Blood Marrow Transplant 2006; 12 (Suppl. 2):13-21.
41. Shin L, Peterson DA. Human mesenchymal stem cell grafts enhance normal and impaired wound healing by recruiting existing endogenous tissue stem/progenitor cells. Stem Cells Transl Med 2013; 2:33-42.
42. Wagner W, Bork S, Horn P etal. Aging and replicative senescence have related effects on human stem and progenitor cells. Open Access 2009; 4:1-13.
43. Kurz EU, Douglas P, Lees-Miller SP. Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. J Biol Chem 2004; 17:53272-53281.
44. Vousden KH, Prives C. Blinded by the SteLight: the growing complexity of p53. Cell 2009; 137:413-431.
45. Kruse J-P, Gu W. Modes of p53 regulation. Cell 2009; 137:609-622.
46. Ju Z, Choudhury AR, Rudolph KL etal. A dual role of p21 in stem cell aging. Acad Sci 2007; 1100:333-344.
47. Zhao T, Xu Y. p53 and stem cells: new developments and new concerns. Trends Cell Biol 2010; 20:170-175.
48. Tsai CC, Chen YJ, Yew TL etal. Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST. Blood 2011; 117:459-469.
49. Brandl A, Meyer M, Bechmann V etal. Oxidative stress induces senescence in human mesenchymal stem cells. Exp Cell Res 2011; 317:1541-1547.
50. + regulatory T cells. Clin Exp Immunol 2009; 156:149-160.
51. + T cell subsets. Cell Immunol 2008; 253:23-30.
52. Fu S, Zhang N, Yopp AC etal. TGF-beta induces Foxp3+ T regulatory cells from CD4+ CD25-precursors. Am J Transplant 2004; 4:1614-1627.
53. Yamagiwa S, Gray JD, Hashimoto S etal. A role for TGFbeta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol 2001; 166:7282-7289.
54. Zheng SG, Gray JD, Ohtsuka K etal. Generation ex vivo of TGFbeta-producing regulatory T cells from CD4+CD25- precursors. J Immunol 2002; 169:4183-18.
55. Sancho D, Gómez M, Sánchez-Madrid F. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol 2005; 26:136-140.
56. Sekar D, Hahn C, Brüne B etal. Apoptotic tumor cells induce IL-27 release from human DCs to activate Treg cells that express CD69 and attenuate cytotoxicity. Eur J Immunol 2012; 42:1585-1598.
57. Kucharz EJ, Brzezinska-Wcislo L, Kotulska A etal. Elevated serum level of interleukin-10 in patients with systemic sclerosis. Clin Rheumatol 1997; 16:638-639.
58. Gruschwitz MS, Hornstein OP. Expression of transforming growth factor type beta on human epidermal dendritic cells. J Invest Dermatol 1992; 99:114-116.
59. Tse WT, Pendleton JD, Beyer WM etal. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75:389-397.
60. Le Blanc K, Rasmusson I, Sundberg B etal. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363:1439-1441.
61. Di Ianni M, Del Papa B, Zei T etal. T regulatory cell separation for clinical application. Transfus Apher Sci 2012; 47:213-216.