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Role of mesenchymal stem cells in leukaemia: Dr. Jekyll or Mr. Hyde?

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Abstract

Mesenchymal stem cells (MSCs) have captured the attention of researchers today due to their multipotent differentiation capacity. Also, they have been successfully applied clinically, in the treatment of various diseases of the heart and musculoskeletal systems, with encouraging results. Their supportive role in haematopoiesis and their anti-inflammatory and immunomodulatory properties have enhanced their contribution towards the improvement of engraftment and the treatment of graft-versus-host disease in patients receiving haematopoietic stem cell transplantation. However, there is a growing body of research that supports the involvement of MSCs in leukaemogenesis with several genetic and functional abnormalities having been detected in the MSCs of leukaemia patients. MSCs also exert leukaemia-enhancing effects and induce chemotherapy resistance in leukaemia cells. This paper addresses the key issues in the therapeutic value as well as the harmful effects of the MSCs in leukaemia with a sharp focus on the recent updates in the published literature.

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References

  1. Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F (2009) The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood 114(16):3367–3375

    Article  CAS  PubMed  Google Scholar 

  2. Qian SW, Li X, Zhang YY, Huang HY, Liu Y, Sun X, Tang QQ (2010) Characterisation of adipocyte differentiation from human mesenchymal stem cells in bone marrow. BMC Dev Biol 10:47

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM (2012) Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater 23:13–27

    CAS  PubMed  Google Scholar 

  4. Sun Y, Chen L, Hou XG, Hou Wk, Dong JJ, Sun L, Tang KX, Wang B, Song J, Li H, Wang KX (2007) Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin producing cells in vitro. Chin Med J 120(9):771–776

    CAS  PubMed  Google Scholar 

  5. Ju S, Teng GJ, Lu H, Jin J, Zhang Y, Zhang A, Ni Y (2010) In vivo differentiation of magnetically labeled mesenchymal stem cells into hepatocytes for cell therapy to repair damaged liver. Invest Radiol 45(10):625–633

    Article  PubMed  Google Scholar 

  6. Tabera S, Perez-Simon JA, Diez-Campelo M, Sanchez-Abarca LI, Blanco B, Lopez A, Benito A, Ocio E, Sánchez-Guijo FM, Cañizo C, San Miguel JF (2008) The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica 93:1301–1309

    Article  CAS  PubMed  Google Scholar 

  7. Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC (2003) Suppression of allogeneic T cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75:389–397

    Article  CAS  PubMed  Google Scholar 

  8. Benvenuto F, Ferrari S, Gerdoni E, Gualandi F, Frassoni F, Pistoia V, Mancardi G, Uccelli A (2007) Human mesenchymal stem cells promote survival of T cells in a quiescent state. Stem Cells 25:1753–1760

    Article  CAS  PubMed  Google Scholar 

  9. Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 23:74–85

    Article  Google Scholar 

  10. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006) Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol 177:2080–2087

    Article  CAS  PubMed  Google Scholar 

  11. Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F (2007) Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation 83:71–76

    Article  PubMed  Google Scholar 

  12. Williams AR, Hare JM (2011) Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 109(8):923–940

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Mafi R, Hindocha S, Mafi P, Griffin M, Khan WS (2011) Sources of adult mesenchymal stem cells applicable for musculoskeletal applications - a systematic review of the literature. Open Orthop J 5(Suppl 2):242–248

    Article  PubMed Central  PubMed  Google Scholar 

  14. Lin Y, Hogan WJ (2011) Clinical application of mesenchymal stem cells in the treatment and prevention of graft-versus-host disease. Adv Haematol 2011:427863

    Google Scholar 

  15. Rhodes LV, Antoon JW, Muir SE, Elliott S, Beckman BS, Burow ME (2010) Effects of human mesenchymal stem cells on ER-positive human breast carcinoma cells mediated through ER-SDF-1/CXCR4 crosstalk. Mol Cancer 9:295

    Article  PubMed Central  PubMed  Google Scholar 

  16. Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K (2010) Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer 127(10):2323–2333

    Article  CAS  PubMed  Google Scholar 

  17. Hsu HS, Lin JH, Hsu TW, Su K, Wang CW, Yang KY, Chiou SH, Hung SC (2012) Mesenchymal stem cells enhance lung cancer initiation through activation of IL-6/JAK2/STAT3 pathway. Lung Cancer 75(2):167–177

    Article  PubMed  Google Scholar 

  18. Jeong JO, Han JW, Kim JM, Cho HJ, Park C, Lee N, Kim DW, Yoon YS (2011) Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ Res 108(11):1340–1347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Wong, RSY (2011) Mesenchymal stem cells: Angels or demons? J Biomed Biotech. Article ID 459510, 8 pages

  20. Garcia S, Bernad A, Martín MC, Cigudosa JC, Garcia-Castro J, de la Fuente R (2010) Pitfalls in spontaneous in vitro transformation of human mesenchymal stem cells. Exp Cell Res 316(9):1648–1650

    Article  CAS  PubMed  Google Scholar 

  21. Torsvik A, Røsland GV, Svendsen A, Molven A, Immervoll H, McCormack E, Lønning PE, Primon M, Sobala E, Tonn JC, Goldbrunner R, Schichor C, Mysliwietz J, Lah TT, Motaln H, Knappskog S, Bjerkvig R (2011) Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track—letter. Cancer Res 70(15):6393–6396

    Article  Google Scholar 

  22. Yen BL, Yan ML (2008) Mesenchymal stem cells and cancer- for better or for worse? J Cancer Mol 4(1):5–9

    CAS  Google Scholar 

  23. Stagg J (2008) Mesenchymal stem cell in cancer. Stem Cell Rev 4(2):119–124

    Article  PubMed  Google Scholar 

  24. Purton, LE, Scadden, DT (2008) The hematopoietic stem cell niche. In: StemBook (ed) The Stem Cell Research Community, StemBook, doi:10.3824/stembook.1.28.1. http://www.stembook.org

  25. Trentin JJ (1971) Determination of bone marrow stem cell differentiation by stromal hemopoietic inductive microenvironments (HIM). Am J Pathol 65:621–628

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Barry FP, Murphy JM (2008) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36(4):568–584

    Article  Google Scholar 

  27. Chao S (2012) Recent progress toward understanding the physiological function of bone marrow mesenchymal stem cells. Immunology 136(2):133–138

    Article  Google Scholar 

  28. Garrett RW, Emerson SG (2009) Bone and blood vessels: the hard and the soft of haematopoietic stem cell niches. Cell Stem Cell 4(6):503–506

    Article  CAS  PubMed  Google Scholar 

  29. Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA (2003) Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 10(2):228–241

    Article  CAS  PubMed  Google Scholar 

  30. Majumdar MK, Thiede MA, Haynesworth SE, Bruder SP, Gerson SL (2000) Human marrow-derived mesenchymal stem cells (MSCs) express haematopoietic cytokines and support long-term haematopoiesis when differentiated toward stromal and osteogenic lineages. J Haematother Stem Cell Res 9(6):841–848

    Article  CAS  Google Scholar 

  31. Alakel N, Jing D, Muller K, Bornhauser M, Ehninger G, Ordemann R (2009) Direct contact with mesenchymal stromal cells affects migratory behavior and gene expression profile of CD133+ hematopoietic stem cells during ex vivo expansion. Exp Haematol 37(4):504–513

    Article  CAS  Google Scholar 

  32. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, Liles WC, Li X, Graham-Evans B, Campbell TB, Calandra G, Bridger G, Dale DC, Srour EF (2005) Rapid mobilization of murine and human haematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 201(8):1302–1318

    Article  Google Scholar 

  33. Méndez-Ferrer S, Lucas D, Battista M, Frenette PS (2008) Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452(7186):442–447

    Article  PubMed  Google Scholar 

  34. Wagner W, Roderburg C, Wein F, Diehlmann A, Frankhauser M, Schubert R, Eckstein V, Ho AD (2007) Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 25(10):2638–2647

    Article  CAS  PubMed  Google Scholar 

  35. Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834

    Article  PubMed Central  PubMed  Google Scholar 

  36. Cheong L, Qasba P, Vanguri P, Thiede MA (2001) Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells. J Cell Physiol 184(1):58–69

    Article  Google Scholar 

  37. Menendez P, Catalina P, Rodríguez R, Melen GJ, Bueno C, Arriero M, García-Sánchez F, Lassaletta A, García-Sanz R, García-Castro J (2009) Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene. J Exp Med 206(13):3131–3141

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Shalapour S, Eckert C, Seeger K, Pfau M, Prada J, Henze G, Blankenstein T, Kammertoens T (2010) Leukaemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukaemia. J Mol Med (Berl) 88(3):249–265

    Article  Google Scholar 

  39. Blau O, Hofmann WK, Baldus CD, Thiel G, Serbent V, Schümann E, Thiel E, Blau IW (2007) Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp Haematol 35(2):221–229

    Article  CAS  Google Scholar 

  40. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT (2010) Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 464(7290):852–857

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM (2003) Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet 33(1):97–101

    Article  CAS  PubMed  Google Scholar 

  42. Lu YL, Yu XQ, Zhu Y, Ba R, Zhu W, Xu WR (2008) Expression of integrins in bone marrow mesenchymal stem cells derived from patients with chronic myeloid leukaemia. Zhongguo Shi Yan Xue Ye XueZaZhi 16(4):755–758

    CAS  Google Scholar 

  43. Zhao ZG, Li WM, Chen ZC, You Y, Zou P (2008) Immunosuppressive properties of mesenchymal stem cells derived from bone marrow of patient with hematological malignant diseases. Leuk Lymphoma 49(11):2187–2195

    Article  CAS  Google Scholar 

  44. Zhu XS, An GY, Song YG, Zhang HM (2011) The research on the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukaemia patients. J Exp Clin Cancer Res 30:47

    Article  Google Scholar 

  45. Zhao ZG, Liang Y, Li K, Li WM, Li QB, Chen ZC, Zou P (2007) Phenotypic and functional comparison of mesenchymal stem cells derived from the bone marrow of normal adults and patients with haematologic malignant diseases. Stem Cells Dev 16(4):637–648

    Article  CAS  PubMed  Google Scholar 

  46. Wei Z, Chen N, Guo H, Wang X, Xu F, Ren Q, Lu S, Liu B, Zhang L, Zhao H (2009) Bone marrow mesenchymal stem cells from leukemia patients inhibit growth and apoptosis in serum-deprived K562 cells. J Exp Clin Cancer Res 28:141

    Article  PubMed Central  PubMed  Google Scholar 

  47. Lin YM, Zhang GZ, Lu ZX, Leng ZX, Bu LS, Gao S (2006) Study of apoptosis gene expression in U937 cells induced by adhesion culture with mesenchymal stem cell. ZhonghuaXueYe XueZaZhi 27(4):249–253

    CAS  Google Scholar 

  48. Gazave E, Lapébie P, Richards GS, Brunet F, Ereskovsky AV, Degnan BM, Borchiellini C, Vervoort M, Renard E (2009) Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes. BMC Evol Biol 9:249

    Article  PubMed Central  PubMed  Google Scholar 

  49. NwaboKamdje AH, Mosna F, Bifari F, Lisi V, Bassi G, Malpeli G, Ricciardi M, Perbellini O, Scupoli MT, Pizzolo G, Krampera M (2011) Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells. Blood 118(2):380–389

    Article  Google Scholar 

  50. Giannoni P, Scaglione S, Quarto R, Narcisi R, Parodi M, Balleari E, Barbieri F, Pattarozzi A, Florio T, Ferrini S, Corte G, de Totero D (2011) An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukaemic cells through STAT3 phosphorylation: a potential role of mesenchymal cells in the disease. Haematologica 96(7):1015–1023

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. de Vasconcellos JF, Laranjeira AB, Zanchin NI, Otubo R, Vaz TH, Cardoso AA, Brandalise SR, Yunes JA (2011) Increased CCL2 and IL-8 in the bone marrow microenvironment in acute lymphoblastic leukemia. Paediatr Blood Cancer 56(4):568–577

    Article  Google Scholar 

  52. Ding W, Nowakowski GS, Knox TR, Boysen JC, Maas ML, Schwager SM, Wu W, Wellik LE, Dietz AB, Ghosh AK, Secreto CR, Medina KL, Shanafelt TD, Zent CS, Call TG, Kay NE (2009) Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression. Br J Haematol 147(4):471–483

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Ding W, Knox TR, Tschumper RC, Wu W, Schwager SM, Boysen JC, Jelinek DF, Kay NE (2010) Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia: implications for an angiogenic switch. Blood 116(16):2984–2993

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Wang ZX, Yang ZM, Zou YW, Li MM, Chen FX, Zhong GY, Guan JM, Wei FG, Wu SZ, He ZT, Wu ZL (2011) Effects of acute lymphoblastic leukaemia children bone marrow mesenchymal stem cells on drug resistance of K562/A02 cell line. Zhongguo Shi Yan Xue Ye XueZaZhi 19(1):19–23

    CAS  Google Scholar 

  55. Kurtova AV, Balakrishnan K, Chen R, Ding W, Schnabl S, Quiroga MP, Sivina M, Wierda WG, Estrov Z, Keating MJ, Shehata M, Jäger U, Gandhi V, Kay NE, Plunkett W, Burger JA (2009) Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance. Blood 114(20):4441–4450

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Lin YM, Zhang GZ, Leng ZX, Lu ZX, Bu LS, Gao S, Yang SJ (2010) Study on the bone marrow mesenchymal stem cells induced drug resistance in the U937 cells and its mechanism. Chin Med J 119(11):905–910

    Google Scholar 

  57. Iwamoto S, Mihara K, Downing JR, Pui CH, Campana D (2007) Mesenchymal cells regulate the response of acute lymphoblastic leukaemia cells to asparaginase. J Clin Invest 117(4):1049–1057

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Pillozzi S, Masselli M, De Lorenzo E, Accordi B, Cilia E, Crociani O, Amedei A, Veltroni M, D’Amico M, Basso G, Becchetti A, Campana D, Arcangeli A (2011) Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers. Blood 117(3):902–914

    Article  CAS  PubMed  Google Scholar 

  59. Niedermeier M, Hennessy BT, Knight ZA, Henneberg M, Hu J, Kurtova AV, Wierda WG, Keating MJ, Shokat KM, Burger JA (2009) Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood 113(22):5549–5557

    Article  CAS  PubMed  Google Scholar 

  60. Burger JA, Peled A (2009) CXCR4 antagonists: targeting the microenvironment in leukaemia and other cancers. Leukaemia 23(1):43–52

    Article  CAS  Google Scholar 

  61. Sarmadi VH, Tong CK, Vidyadaran S, Abdullah M, Seow HF, Ramasamy R (2010) Mesenchymal stem cells inhibit proliferation of lymphoid origin haematopoietic tumour cells by inducing cell cycle arrest. Med J Malaysia 65(3):202–207

    Google Scholar 

  62. Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C, Zhao RC (2009) Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukaemia 23(5):925–933

    Article  CAS  Google Scholar 

  63. Zhang HM, Zhang LS (2009) Influence of human bone marrow mesenchymal stem cells on proliferation of chronic myeloid leukemia cells. Chin J Cancer 28(1):29–32

    Google Scholar 

  64. Baker D, Cole C, Price J, Phillips M (2004) Allogeneic bone marrow transplantation in juvenile myelomonocytic leukemia without total body irradiation. J Paediatr Haematol Oncol 26(3):200–203

    Article  Google Scholar 

  65. Cutler C, Antin JH (2001) Peripheral blood stem cells for allogeneic transplantation: a review. Stem Cells 19(2):108–117

    Article  CAS  PubMed  Google Scholar 

  66. Wagner J, Barker J, DeFor T, Baker K, Blazar B, Eide C, Goldman A, Kersey J, Krivit W, MacMillan M, Orchard P, Peters C, Weisdorf D, Ramsay N, Davies S (2002) Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 100:1611–1618

    CAS  PubMed  Google Scholar 

  67. Shah NP (2007) Medical treatment of chronic myeloid leukaemia. Am Soc Haematol Educ Program 2007:371–375

    Article  Google Scholar 

  68. Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M (2009) The allogeneic graft-versus-cancer effect. British J Haematol 147:614–633

    Article  Google Scholar 

  69. Lee ST, Maeng HY, Chwae YJ, Oh DJ, Kim YM, Yang WI (2008) Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model. Int J Haematol 87(3):327–337

    Article  CAS  Google Scholar 

  70. Angelopoulou M, Novelli E, Grove JE, Rinder HM, Civin C, Cheng L, Krause DS (2003) Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp Haematol 31(5):413–420

    Article  CAS  Google Scholar 

  71. MacMillan ML, Blazar BR, DeFor TE, Wagner JE (2009) Transplantation of ex vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I-II clinical trial. Bone Marrow Transpl 43:447–454

    Article  CAS  Google Scholar 

  72. Liu K, Chen Y, Zeng Y, Xu L, Liu D, Chen H, Zhang X, Han W, Wang Y, Zhao T, Wang J, Wang J, Han Q, Zhao C, Huang X (2011) Coinfusion of mesenchymal stromal cells facilitates platelet recovery without increasing leukemia recurrence in haploidentical hematopoietic stem cell transplantation: a randomized, controlled clinical study. Stem Cell Dev 20(10):1679–1685

    Article  CAS  Google Scholar 

  73. Ceredig R (2011) Graft-versus-host disease: who’s responsible? Immunol Cell Biol 2011:1–2

    Google Scholar 

  74. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transpl 11(12):945–956

    Article  Google Scholar 

  75. Lim JH, Lee MH, Yi HG, Kim CS, Kim JH, Song SU (2010) Mesenchymal stromal cells for steroid-refractory acute graft-versus-host disease: a report of two cases. Int J Haematol 92(1):204–207

    Article  Google Scholar 

  76. Lucchini G, Introna M, Dander E, Rovelli A, Balduzzi A, Bonanomi S, Salvadè A, Capelli C, Belotti D, Gaipa G, Perseghin P, Vinci P, Lanino E, Chiusolo P, Orofino MG, Marktel S, Golay J, Rambaldi A, Biondi A, D’Amico G, Biagi E (2010) Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population. Biol Blood Marrow Transpl 16(9):1293–1301

    Article  Google Scholar 

  77. Pérez-Simon JA, López-Villar O, Andreu EJ, Rifón J, Muntion S, Campelo MD, Sánchez-Guijo FM, Martinez C, Valcarcel D, Cañizo CD (2011) Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica 96(7):1072–1076

    Article  PubMed Central  PubMed  Google Scholar 

  78. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O, Developmental Committee of the European Group for Blood and Marrow Transplantation (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371(9624):1579–1586

    Google Scholar 

  79. Paczesny S, Krijanovski OI, Braun TM, Choi SW, Clouthier SG, Kuick R, Misek DE, Cooke KR, Kitko CL, Weyand A, Bickley D, Jones D, Whitfield J, Reddy P, Levine JE, Hanash SM, Ferrara JL (2009) A biomarker panel for acute graft-versus-host disease. Blood 113(2):273–278

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Dander E, Lucchini G, Vinci P, Introna M, Masciocchi F, Perseghin P, Balduzzi A, Bananomi S, Longoni D, Gaipas G, Belotti D, Parma M, Algarotti A, Capelli C, Golay J, Rovelli Am Rambaldi A, Biondi A, Biagi E, D’Amico G (2012) Mesenchymal stromal cells for the treatment of graft-versus-host disease: understanding the in vivo biological effect through patient immune monitoring. Leukaemia 26:1681–1684

    Article  CAS  Google Scholar 

  81. Von Bahr LL, Sundberg BB, Lönnies LL, der San BB, Karbach HH, Hägglund HH, Ljungman PP, Gustafsson BB, Karlsson HH, Le Blanc KK, Ringdén OO (2012) Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transpl 18(4):557–564

    Article  Google Scholar 

  82. Bernardo ME, Ball LM, Cometa AM, Roelofs H, Zecca M, Avanzini MA, Bertaina A, Vinti L, Lankester A, Maccario R, Ringden O, Le Blanc K, Egeler RM, Fibbe WE, Locatelli F (2011) Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation. Bone Marrow Transpl 46(2):200–207

    Article  CAS  Google Scholar 

  83. Kuzmina LA, Petinati NA, Parovichnikova EN, Lubimova LS, Gribanova EO, Gaponova TV, Shipounova IN, Zhironkina OA, Bigildeev AE, Svinarev DA, Drize NJ and Sacvhenko VG (2012) Multipotent mesenchymal stromal cells for the prophylaxis of acute graft-versus-host disease—a phase II study. Stem Cells Int 968213:8

  84. Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A, Fillet G, Beguin Y (2010) Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transpl 16(6):838–847

    Article  Google Scholar 

  85. Hodgkinson CP, Gomez JA, Mirotsou M, Dzau VJ (2010) Genetic engineering of mesenchymal stem cells and its application in human disease therapy. Hum Gene Ther 21:1513–1526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Shah K (2012) Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev 64(8):739–748

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Morini MR, Sun XY, Rayat J, Dai D, Ao Z, He Z, Verchere D, Dai LJ, Warnock GL (2012) TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells. Cancer Gene Ther 19:652–658

    Article  Google Scholar 

  88. Bao Q, Zhao Y, Niess H, Conrad C, Schwarz B, Jauch KW, Huss R, Nelson PJ, Bruns CJ (2012) Mesenchymal stem cell-based tumuor-targeted gene therapy in gastrointestinal cancer. Stem Cells Dev 21(13):2355–2363

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Song F, Xing Q, Song KD, Liu J, Ji GC, Ma YF, Lio TQ, Wei MH, Ma XH (2011) Inhibitory effects of cytosine deaminase gene-transfected bone marrow mesenchymal stem cells on glioma cell proliferation. Neural Regen Res 6(16):1238–1242

    Google Scholar 

  90. Hakkarainen T, Sarkioja M, Lehenkari P, Miettinen S, Ylikomi T, Suuronen R, Desmond RA, Kanerva A, Hemminki A (2007) Human mesenchymal stem cells lack tumor tropism but enhance the antitumor activity of oncolytic adenoviruses in orthotopic lung and breast tumors. Hum Gene Ther 18:627–641

    Article  CAS  PubMed  Google Scholar 

  91. Stoff-Khalili MA, Rivera AA, Mathis JM, Banerjee NS, Moon AS, Hess A, Rocconi RP, Numnum TM, Everts M, Chow LT, Douglas JT, Siegal GP, Zhu ZB, Bender HG, Dall P, Stoff A, Pereboeva L, Curiel DT (2007) Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma. Breast Cancer Res Treat 105:157–167

    Article  PubMed  Google Scholar 

  92. Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1997) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107:275–281

    Article  Google Scholar 

  93. Greco SJ, Rameshwar P (2012) Mesenchymal stem cells in drug/gene delivery: implications for cell therapy. Ther Deliv 3(8):997–1004

    Article  CAS  PubMed  Google Scholar 

  94. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26):1650–1659

    Article  CAS  PubMed  Google Scholar 

  95. Kidd S, Spaeth E, Klopp A, Andreeff M, Hall B, Marini FC (2008) The (in) auspicious role of mesenchymal stromal cells in cancer: be it friend or foe. Cytotherapy 10(7):657–667

    Article  CAS  PubMed  Google Scholar 

  96. Andreeff M, Studeny M, Dembinski J, Konopleva M, Wang RY, Yang HY, Champlin JFRE, Lang F, Marini FC (2004) Mesenchymal stem cells as delivery systems for cancer and leukemia gene therapy. J Clin Oncol ASCO annual meeting proceedings (post-meeting edition) 22(14S):3194

  97. Li X, Lu Y, Huang W, Xu H, Chen X, Geng Q, Fan H, Tan Y, Xue G, Jiang X (2006) In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukaemia. Haematol Oncol 24(3):151–158

    Article  CAS  Google Scholar 

  98. Min CK, Kim BG, Park G, Cho B, Oh IH (2007) IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transpl 39(10):637–645

    Article  CAS  Google Scholar 

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Correspondence to Rebecca S. Y. Wong.

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Wong, R.S.Y., Cheong, SK. Role of mesenchymal stem cells in leukaemia: Dr. Jekyll or Mr. Hyde?. Clin Exp Med 14, 235–248 (2014). https://doi.org/10.1007/s10238-013-0247-4

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  • DOI: https://doi.org/10.1007/s10238-013-0247-4

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