Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells

Journal of Biomedical Science

B-LinjuYen⁴  Huey-Kang Sytwu¹  Ko-Jiunn Liu⁵  Men-Luh Yen²  Pei-Min Chen³ 

[1] Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan;Department of Primary Care Medicine, and Department of Obstetrics/Gynecology, College of Medicine, National Taiwan University and Hospital, Taipei, Taiwan;Regenerative Medicine Research Group, Institute of Cellular and System Medicine, National Health Research Institutes (NHRI), Zhunan, Taiwan;Department of Obstetrics/Gynecology, Cathay General Hospital Shiji, Taipei, Taiwan;National Institute of Cancer Research, NHRI, Tainan, Taiwan

关键词: major histocompatibility complex (MHC) molecules;    dendritic cells;    natural killer lymphocytes;    T lymphocytes;    immunomodulation;    multilineage differentiation;    fetal;    bone marrow;    mesenchymal stem cells;   

Others  :  833201
DOI  :  10.1186/1423-0127-18-49

 received in 2011-04-29, accepted in 2011-07-18,  发布年份 2011

【 摘 要 】

In recent years, a large number of studies have contributed to our understanding of the immunomodulatory mechanisms used by multipotent mesenchymal stem cells (MSCs). Initially isolated from the bone marrow (BM), MSCs have been found in many tissues but the strong immunomodulatory properties are best studied in BM MSCs. The immunomodulatory effects of BM MSCs are wide, extending to T lymphocytes and dendritic cells, and are therapeutically useful for treatment of immune-related diseases including graft-versus-host disease as well as possibly autoimmune diseases. However, BM MSCs are very rare cells and require an invasive procedure for procurement. Recently, MSCs have also been found in fetal-stage embryo-proper and extra-embryonic tissues, and these human fetal MSCs (F-MSCs) have a higher proliferative profile, and are capable of multilineage differentiation as well as exert strong immunomodulatory effects. As such, these F-MSCs can be viewed as alternative sources of MSCs. We review here the current understanding of the mechanisms behind the immunomodulatory properties of BM MSCs and F-MSCs. An increase in our understanding of MSC suppressor mechanisms will offer insights for prevalent clinical use of these versatile adult stem cells in the near future.

【 授权许可】

   
2011 Chen et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284(5411):143-147.
• [2]Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997, 276(5309):71-74.
• [3]Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP: Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968, 6(2):230-247.
• [4]Brooke G, Cook M, Blair C, Han R, Heazlewood C, Jones B, Kambouris M, Kollar K, McTaggart S, Pelekanos R, et al.: Therapeutic applications of mesenchymal stromal cells. Semin Cell Dev Biol 2007, 18(6):846-858.
• [5]Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH: Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001, 7(2):211-228.
• [6]Sottile V, Halleux C, Bassilana F, Keller H, Seuwen K: Stem cell characteristics of human trabecular bone-derived cells. Bone 2002, 30(5):699-704.
• [7]Noth U, Osyczka AM, Tuli R, Hickok NJ, Danielson KG, Tuan RS: Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J Orthop Res 2002, 20(5):1060-1069.
• [8]Yen BL, Huang HI, Chien CC, Jui HY, Ko BS, Yao M, Shun CT, Yen ML, Lee MC, Chen YC: Isolation of multipotent cells from human term placenta. Stem Cells 2005, 23(1):3-9.
• [9]Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH: Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 2004, 103(5):1669-1675.
• [10]Tsai MS, Lee JL, Chang YJ, Hwang SM: Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod 2004, 19(6):1450-1456.
• [11]Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC: Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells 2004, 22(7):1330-1337.
• [12]Gotherstrom C, Ringden O, Tammik C, Zetterberg E, Westgren M, Le Blanc K: Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol 2004, 190(1):239-245.
• [13]Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM: Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 2001, 98(8):2396-2402.
• [14]Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8(4):315-317.
• [15]Picinich SC, Mishra PJ, Mishra PJ, Glod J, Banerjee D: The therapeutic potential of mesenchymal stem cells. Cell- & tissue-based therapy. Expert Opin Biol Ther 2007, 7(7):965-973.
• [16]Giordano A, Galderisi U, Marino IR: From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 2007, 211(1):27-35.
• [17]Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, et al.: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002, 30(1):42-48.
• [18]Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O: HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003, 31(10):890-896.
• [19]Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM: Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002, 99(10):3838-3843.
• [20]Dean RM, Bishop MR: Graft-versus-host disease: emerging concepts in prevention and therapy. Curr Hematol Rep 2003, 2(4):287-294.
• [21]Barker JN, Wagner JE: Umbilical cord blood transplantation: current practice and future innovations. Crit Rev Oncol Hematol 2003, 48(1):35-43.
• [22]Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, et al.: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008, 371(9624):1579-1586.
• [23]Jurewicz M, Yang S, Augello A, Godwin JG, Moore RF, Azzi J, Fiorina P, Atkinson M, Sayegh MH, Abdi R: Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes. Diabetes 2010, 59(12):3139-3147.
• [24]Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, et al.: Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009, 15(1):42-49.
• [25]Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G: Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum 2007, 56(4):1175-1186.
• [26]Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O: Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004, 363(9419):1439-1441.
• [27]Barry FP, Murphy JM, English K, Mahon BP: Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft. Stem Cells Dev 2005, 14(3):252-265.
• [28]Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA, McIntosh KR, Mosca JD: Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003, 10(2):228-241.
• [29]Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC: Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003, 75(3):389-397.
• [30]Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, Deans RJ, McIntosh KR: T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 2005, 12(1):47-57.
• [31]Stenderup K, Justesen J, Clausen C, Kassem M: Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003, 33(6):919-926.
• [32]de Braud F, Khayat D, Kroon BB, Valdagni R, Bruzzi P, Cascinelli N: Malignant melanoma. Crit Rev Oncol Hematol 2003, 47(1):35-63.
• [33]Erices A, Conget P, Minguell JJ: Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000, 109(1):235-242.
• [34]Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE: Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 2005, 23(2):220-229.
• [35]In 't Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE, Kanhai HH: Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003, 102(4):1548-1549.
• [36]Bachmann MF, Kohler G, Ecabert B, Mak TW, Kopf M: Lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J Immunol 1999, 163(3):1128-1131.
• [37]Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K: Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells 2004, 22(5):649-658.
• [38]Wulf GG, Viereck V, Hemmerlein B, Haase D, Vehmeyer K, Pukrop T, Glass B, Emons G, Trumper L: Mesengenic progenitor cells derived from human placenta. Tissue Eng 2004, 10(7-8):1136-1147.
• [39]In 't Anker PS, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GM, Claas FH, Fibbe WE, Kanhai HH: Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 2004, 22(7):1338-1345.
• [40]Chang CJ, Yen ML, Chen YC, Chien CC, Huang HI, Bai CH, Yen BL: Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells 2006, 24(11):2466-2477.
• [41]Chiavegato A, Bollini S, Pozzobon M, Callegari A, Gasparotto L, Taiani J, Piccoli M, Lenzini E, Gerosa G, Vendramin I, et al.: Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. J Mol Cell Cardiol 2007, 42(4):746-759.
• [42]Hao L, Zhang C, Chen XH, Zou ZM, Zhang X, Kong PY, Liang X, Gao L, Peng XG, Sun AH, et al.: Human umbilical cord blood-derived stromal cells suppress xenogeneic immune cell response in vitro. Croat Med J 2009, 50(4):351-360.
• [43]Ilancheran S, Michalska A, Peh G, Wallace EM, Pera M, Manuelpillai U: Stem cells derived from human fetal membranes display multilineage differentiation potential. Biol Reprod 2007, 77(3):577-588.
• [44]Kim J, Lee Y, Kim H, Hwang KJ, Kwon HC, Kim SK, Cho DJ, Kang SG, You J: Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells. Cell Prolif 2007, 40(1):75-90.
• [45]Lu LL, Liu YJ, Yang SG, Zhao QJ, Wang X, Gong W, Han ZB, Xu ZS, Lu YX, Liu D, et al.: Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 2006, 91(8):1017-1026.
• [46]Oh W, Kim DS, Yang YS, Lee JK: Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cell Immunol 2008, 251(2):116-123.
• [47]Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, Surbek DV: Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol 2006, 194(3):664-673.
• [48]Roubelakis MG, Pappa KI, Bitsika V, Zagoura D, Vlahou A, Papadaki HA, Antsaklis A, Anagnou NP: Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev 2007, 16(6):931-952.
• [49]Terada S, Matsuura K, Enosawa S, Miki M, Hoshika A, Suzuki S, Sakuragawa N: Inducing proliferation of human amniotic epithelial (HAE) cells for cell therapy. Cell Transplant 2000, 9(5):701-704.
• [50]Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, Xu J: The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 2009, 126(2):220-232.
• [51]Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D, McIntosh KR: Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells 2008, 26(11):2865-2874.
• [52]Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D: Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells 2006, 24(3):781-792.
• [53]Li C, Zhang W, Jiang X, Mao N: Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells. Cell Tissue Res 2007, 330(3):437-446.
• [54]Wolbank S, Peterbauer A, Fahrner M, Hennerbichler S, van Griensven M, Stadler G, Redl H, Gabriel C: Dose-dependent immunomodulatory effect of human stem cells from amniotic membrane: a comparison with human mesenchymal stem cells from adipose tissue. Tissue Eng 2007, 13(6):1173-1183.
• [55]Magatti M, De Munari S, Vertua E, Gibelli L, Wengler GS, Parolini O: Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 2008, 26(1):182-192.
• [56]Bailo M, Soncini M, Vertua E, Signoroni PB, Sanzone S, Lombardi G, Arienti D, Calamani F, Zatti D, Paul P, et al.: Engraftment potential of human amnion and chorion cells derived from term placenta. Transplantation 2004, 78(10):1439-1448.
• [57]Li H, Niederkorn JY, Neelam S, Mayhew E, Word RA, McCulley JP, Alizadeh H: Immunosuppressive factors secreted by human amniotic epithelial cells. Invest Ophthalmol Vis Sci 2005, 46(3):900-907.
• [58]Aggarwal S, Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005, 105(4):1815-1822.
• [59]Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F, et al.: Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006, 24(2):386-398.
• [60]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.
• [61]Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F: Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005, 105(7):2821-2827.
• [62]Benvenuto F, Ferrari S, Gerdoni E, Gualandi F, Frassoni F, Pistoia V, Mancardi G, Uccelli A: Human mesenchymal stem cells promote survival of T cells in a quiescent state. Stem Cells 2007, 25(7):1753-1760.
• [63]Zhou L, Chong MM, Littman DR: Plasticity of CD4+ T cell lineage differentiation. Immunity 2009, 30(5):646-655.
• [64]Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, Miller RH: 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.
• [65]Rafei M, Campeau PM, Aguilar-Mahecha A, Buchanan M, Williams P, Birman E, Yuan S, Young YK, Boivin MN, Forner K, et al.: 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(10):5994-6002.
• [66]Ghannam S, Pene J, Torcy-Moquet G, Jorgensen C, Yssel H: Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol 2010, 185(1):302-312.
• [67]Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, Daudt L, Ibatici A, Piaggio G, Pozzi S, et al.: 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.
• [68]Riley JL, June CH, Blazar BR: Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity 2009, 30(5):656-665.
• [69]Shevach EM: Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009, 30(5):636-645.
• [70]Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, Sakaguchi S: Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999, 162(9):5317-5326.
• [71]English K, Ryan JM, Tobin L, Murphy MJ, Barry FP, Mahon BP: Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells. Clin Exp Immunol 2009, 156(1):149-160.
• [72]Prevosto C, Zancolli M, Canevali P, Zocchi MR, Poggi A: Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 2007, 92(7):881-888.
• [73]Di Ianni M, Del Papa B, De Ioanni M, Moretti L, Bonifacio E, Cecchini D, Sportoletti P, Falzetti F, Tabilio A: Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 2008, 36(3):309-318.
• [74]Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas-Freiss N, et al.: 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.
• [75]Batten P, Sarathchandra P, Antoniw JW, Tay SS, Lowdell MW, Taylor PM, Yacoub MH: Human mesenchymal stem cells induce T cell anergy and downregulate T cell allo-responses via the TH2 pathway: relevance to tissue engineering human heart valves. Tissue Eng 2006, 12(8):2263-2273.
• [76]Rasmusson I: Immune modulation by mesenchymal stem cells. Exp Cell Res 2006, 312(12):2169-2179.
• [77]Groh ME, Maitra B, Szekely E, Koc ON: Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol 2005, 33(8):928-934.
• [78]Rasmusson I, Ringden O, Sundberg B, Le Blanc K: Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res 2005, 305(1):33-41.
• [79]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.
• [80]Meisel R, Zibert A, Laryea M, Gobel U, Daubener 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.
• [81]Plumas J, Chaperot L, Richard MJ, Molens JP, Bensa JC, Favrot MC: Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 2005, 19(9):1597-1604.
• [82]Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, Anegon I, Cuturi MC: A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 2007, 110(10):3691-3694.
• [83]Nasef A, Mazurier C, Bouchet S, Francois S, Chapel A, Thierry D, Gorin NC, Fouillard L: Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol 2008, 253(1-2):16-22.
• [84]Gieseke F, Schutt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, Muller I: Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood 2007, 110(6):2197-2200.
• [85]Nasef A, Mathieu N, Chapel A, Frick J, Francois S, Mazurier C, Boutarfa A, Bouchet S, Gorin NC, Thierry D, et al.: Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation 2007, 84(2):231-237.
• [86]Gieseke F, Bohringer J, Bussolari R, Dominici M, Handgretinger R, Muller I: Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood 2010, 116(19):3770-3779.
• [87]Sioud M, Mobergslien A, Boudabous A, Floisand Y: Mesenchymal stem cell-mediated T cell suppression occurs through secreted galectins. Int J Oncol 2011, 38(2):385-390.
• [88]Liotta F, Angeli R, Cosmi L, Fili L, Manuelli C, Frosali F, Mazzinghi B, Maggi L, Pasini A, Lisi V, et al.: 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.
• [89]Wang D, Chen K, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Bayard F, Zhu D, Han ZC: CD14+ monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells. Exp Cell Res 2010, 316(15):2414-2423.
• [90]Cutler AJ, Limbani V, Girdlestone J, Navarrete CV: Umbilical cord-derived mesenchymal stromal cells modulate monocyte function to suppress T cell proliferation. J Immunol 2010, 185(11):6617-6623.
• [91]Chen K, Wang D, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Zhu D, Bayard F, Han ZC: Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol 2010, 135(3):448-458.
• [92]Girdlestone J, Limbani VA, Cutler AJ, Navarrete CV: Efficient expansion of mesenchymal stromal cells from umbilical cord under low serum conditions. Cytotherapy 2009, 11(6):738-748.
• [93]Zhang Y, Li C, Jiang X, Zhang S, Wu Y, Liu B, Tang P, Mao N: Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells. Exp Hematol 2004, 32(7):657-664.
• [94]Roelen DL, van der Mast BJ, in't Anker PS, Kleijburg C, Eikmans M, van Beelen E, de Groot-Swings GM, Fibbe WE, Kanhai HH, Scherjon SA, et al.: Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells. Hum Immunol 2009, 70(1):16-23.
• [95]Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB: Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One 2010, 5(2):e9016..
• [96]Jones EY, Fugger L, Strominger JL, Siebold C: MHC class II proteins and disease: a structural perspective. Nat Rev Immunol 2006, 6(4):271-282.
• [97]Steinman RM, Pack M, Inaba K: Dendritic cells in the T-cell areas of lymphoid organs. Immunol Rev 1997, 156:25-37.
• [98]Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N: Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005, 105(10):4120-4126.
• [99]Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L: MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood 2009, 113(26):6576-6583.
• [100]Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J: Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 2005, 105(5):2214-2219.
• [101]Li YP, Paczesny S, Lauret E, Poirault S, Bordigoni P, Mekhloufi F, Hequet O, Bertrand Y, Ou-Yang JP, Stoltz JF, et al.: Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the Notch pathway. J Immunol 2008, 180(3):1598-1608.
• [102]Chan WK, Lau AS, Li JC, Law HK, Lau YL, Chan GC: MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge. Exp Hematol 2008, 36(11):1545-1555.
• [103]Stagg J, Pommey S, Eliopoulos N, Galipeau J: Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood 2006, 107(6):2570-2577.
• [104]Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, Rameshwar P: Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 2006, 107(12):4817-4824.
• [105]Francois M, Romieu-Mourez R, Stock-Martineau S, Boivin MN, Bramson JL, Galipeau J: Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties. Blood 2009, 114(13):2632-2638.
• [106]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.
• [107]Romieu-Mourez R, Francois M, Boivin MN, Bouchentouf M, Spaner DE, Galipeau J: Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype. J Immunol 2009, 182(12):7963-7973.
• [108]Pevsner-Fischer M, Morad V, Cohen-Sfady M, Rousso-Noori L, Zanin-Zhorov A, Cohen S, Cohen IR, Zipori D: Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood 2007, 109(4):1422-1432.
• [109]Tomchuck SL, Zwezdaryk KJ, Coffelt SB, Waterman RS, Danka ES, Scandurro AB: Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells 2008, 26(1):99-107.
• [110]Opitz CA, Litzenburger UM, Lutz C, Lanz TV, Tritschler I, Koppel A, Tolosa E, Hoberg M, Anderl J, Aicher WK, et al.: 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.
• [111]Kern S, Eichler H, Stoeve J, Kluter H, Bieback K: Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006, 24(5):1294-1301.
• [112]Parolini O, Alviano F, Bagnara GP, Bilic G, Buhring HJ, Evangelista M, Hennerbichler S, Liu B, Magatti M, Mao N, et al.: Isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells 2008, 26(2):300-311.
• [113]Magatti M, De Munari S, Vertua E, Nassauto C, Albertini A, Wengler GS, Parolini O: Amniotic mesenchymal tissue cells inhibit dendritic cell differentiation of peripheral blood and amnion resident monocytes. Cell Transplant 2009, 18(8):899-914.
• [114]Kronsteiner B, Peterbauer-Scherb A, Grillari-Voglauer R, Redl H, Gabriel C, van Griensven M, Wolbank S: Human mesenchymal stem cells and renal tubular epithelial cells differentially influence monocyte-derived dendritic cell differentiation and maturation. Cell Immunol 2011, 267(1):30-38.
• [115]van den Berk LC, Roelofs H, Huijs T, Siebers-Vermeulen KG, Raymakers RA, Kogler G, Figdor CG, Torensma R: Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells. Immunology 2009, 128(4):564-572.
• [116]Moretta A, Locatelli F, Moretta L: Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias. Immunol Rev 2008, 224:58-69.
• [117]Caligiuri MA: Human natural killer cells. Blood 2008, 112(3):461-469.
• [118]Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M: Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006, 24(1):74-85.
• [119]Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, 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.
• [120]Poggi A, Zocchi MR: Antigen presenting cells and stromal cells trigger human natural killer lymphocytes to autoreactivity: evidence for the involvement of natural cytotoxicity receptors (NCR) and NKG2D. Clin Dev Immunol 2006, 13(2-4):325-336.
• [121]Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, 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.
• [122]Rouas-Freiss N, Goncalves RM, Menier C, Dausset J, Carosella ED: Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci USA 1997, 94(21):11520-11525.
• [123]Apps R, Gardner L, Moffett A: A critical look at HLA-G. Trends Immunol 2008, 29(7):313-321.
• [124]Carosella ED, Favier B, Rouas-Freiss N, Moreau P, Lemaoult J: Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood 2008, 111(10):4862-4870.
• [125]LeMaoult J, Zafaranloo K, Le Danff C, Carosella ED: HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells. FASEB J 2005, 19(6):662-664.
• [126]La Rocca G, Anzalone R, Corrao S, Magno F, Loria T, Lo Iacono M, Di Stefano A, Giannuzzi P, Marasa L, Cappello F, et al.: Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochem Cell Biol 2009, 131(2):267-282.
• [127]Liu KJ, Wang JC, Chang CJ, Hu HI, Hsu PJ, Wu YC, Bai CH, Sytwu HK, Yen BL: Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes. Cell Transplant 2011, in press.
• [128]Gaunt G, Ramin K: Immunological tolerance of the human fetus. Am J Perinatol 2001, 18(6):299-312.
• [129]Moffett-King A: Natural killer cells and pregnancy. Nat Rev Immunol 2002, 2(9):656-663.
• [130]Deeg HJ: How I treat refractory acute GVHD. Blood 2007, 109(10):4119-4126.
• [131]Aksu AE, Horibe E, Sacks J, Ikeguchi R, Breitinger J, Scozio M, Unadkat J, Feili-Hariri M: Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats. Clin Immunol 2008, 127(3):348-358.
• [132]Zhou HP, Yi DH, Yu SQ, Sun GC, Cui Q, Zhu HL, Liu JC, Zhang JZ, Wu TJ: Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft. Transplant Proc 2006, 38(9):3046-3051.
• [133]Yanez R, Lamana ML, Garcia-Castro J, Colmenero I, Ramirez M, Bueren JA: Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells 2006, 24(11):2582-2591.
• [134]Kim DW, Chung YJ, Kim TG, Kim YL, Oh IH: Cotransplantation of third-party mesenchymal stromal cells can alleviate single-donor predominance and increase engraftment from double cord transplantation. Blood 2004, 103(5):1941-1948.
• [135]Ge W, Jiang J, Baroja ML, 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. Am J Transplant 2009, 9(8):1760-1772.
• [136]Popp FC, Eggenhofer E, Renner P, Slowik P, Lang SA, Kaspar H, Geissler EK, Piso P, Schlitt HJ, Dahlke MH: Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate. Transpl Immunol 2008, 20(1-2):55-60.
• [137]von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, et al.: Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 2009, 43(3):245-251.
• [138]Fang B, Song Y, Liao L, Zhang Y, Zhao RC: Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. Transplant Proc 2007, 39(10):3358-3362.
• [139]Muller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F, Dominici M, Greil J, 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.
• [140]Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, et al.: Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 2005, 11(5):389-398.
• [141]Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z, Li B, Xu C, Li Y, et al.: 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(3):593-599.
• [142]Taupin P: OTI-010 Osiris Therapeutics/JCR Pharmaceuticals. Curr Opin Investig Drugs 2006, 7(5):473-481.
• [143]Vianello F, Dazzi F: Mesenchymal stem cells for graft-versus-host disease: a double edged sword? Leukemia 2008, 22(3):463-465.
• [144]Sundin M, Ringden O, Sundberg B, Nava S, Gotherstrom C, Le Blanc K: No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 2007, 92(9):1208-1215.
• [145]Le Blanc K, Ringden O: Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005, 11(5):321-334.
• [146]Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J: Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 2005, 106(13):4057-4065.
• [147]Bensidhoum M, Chapel A, Francois S, Demarquay C, Mazurier C, Fouillard L, Bouchet S, Bertho JM, Gourmelon P, Aigueperse J, et al.: Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment. Blood 2004, 103(9):3313-3319.
• [148]Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, Locatelli F, Fibbe WE: Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood 2007, 110(7):2764-2767.
• [149]Behre G, Theurich S, Weber T, Christopeit M: Reply to 'The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rates in hematologic malignancy patients: outcome of a pilot clinical study'. In Leukemia Edited by Ning, et al. 2009, 23(1):178. author reply 179-180
• [150]Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, Ljungman P, Lonnies H, Nava S, Ringden O: Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 2007, 21(8):1733-1738.
• [151]in 't Anker PS, Noort WA, Kruisselbrink AB, Scherjon SA, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE: Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34+ cells in NOD/SCID mice. Exp Hematol 2003, 31(10):881-889.
• [152]Ringden O, Remberger M, Svahn BM, Barkholt L, Mattsson J, Aschan J, Le Blanc K, Gustafsson B, Hassan Z, Omazic B, et al.: Allogeneic hematopoietic stem cell transplantation for inherited disorders: experience in a single center. Transplantation 2006, 81(5):718-725.
• [153]Kong XY, Cai Z, Pan L, Zhang L, Shu J, Dong YL, Yang N, Li Q, Huang XJ, Zuo PP: Transplantation of human amniotic cells exerts neuroprotection in MPTP-induced Parkinson disease mice. Brain Res 2008, 1205:108-115.
• [154]Zhao P, Ise H, Hongo M, Ota M, Konishi I, Nikaido T: Human amniotic mesenchymal cells have some characteristics of cardiomyocytes. Transplantation 2005, 79(5):528-535.
• [155]Kubo M, Sonoda Y, Muramatsu R, Usui M: Immunogenicity of human amniotic membrane in experimental xenotransplantation. Invest Ophthalmol Vis Sci 2001, 42(7):1539-1546.
• [156]Walther G, Gekas J, Bertrand OF: Amniotic stem cells for cellular cardiomyoplasty: promises and premises. Catheter Cardiovasc Interv 2009, 73(7):917-924.
• [157]Prather WR, Toren A, Meiron M: Placental-derived and expanded mesenchymal stromal cells (PLX-I) to enhance the engraftment of hematopoietic stem cells derived from umbilical cord blood. Expert Opin Biol Ther 2008, 8(8):1241-1250.
• [158]Hiwase SD, Dyson PG, To LB, Lewis ID: Cotransplantation of placental mesenchymal stromal cells enhances single and double cord blood engraftment in nonobese diabetic/severe combined immune deficient mice. Stem Cells 2009, 27(9):2293-2300.