Abstract
Engraftment failure is a rare but life-threatening complication of hematopoietic cell transplantation (HCT). Newer approaches to HCT, including use of haploidentical donors, umbilical cord blood (UCB) transplant, nonmyeloablative and reduced-intensity conditioning regimens, appear to have an increased risk of graft failure. Multipotent mesenchymal stromal cells (MSCs) are essential bone marrow components that have the potential to differentiate in vitro into tissues along mesenchymal lineages, including bone marrow stroma. This regenerative potential, coupled with the capability to secrete cytokines and growth factors, suggests that MSCs would facilitate and promote hematopoiesis. Moreover, MSCs have immunoregulatory properties and thus could have an additional application in the setting of HCT by reducing both graft rejection and graft-versus-host disease. Initial trials have demonstrated the safety and feasibility of infusion of ex vivo-expanded autologous and allogeneic MSCs. Results from these early trials suggested MSCs may enhance hematopoiesis when infused at the time of HCT; however, subsequent trials have not yet provided confirmation that MSCs accelerate hematopoietic recovery when given shortly after HCT. Ongoing research initiatives include use of MSC infusions for patients who have some evidence of regenerating marrow but have delayed or incomplete hematopoiesis.
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References
Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354:1813–1826
Leung AY, Kwong YL (2010) Haematopoietic stem cell transplantation: current concepts and novel therapeutic strategies. Br Med Bull 93:85–103
Ho VT, Soiffer RJ (2001) The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 98:3192–3204
Maitra B, Szekely E, Gjini K et al (2004) Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant 33:597–604
Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247
Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317
Bernardo ME, Locatelli F, Fibbe WE (2009) Mesenchymal stromal cells. Ann N Y Acad Sci 1176:101–117
Devine SM, Cobbs C, Jennings M et al (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101:2999–3001
Hare JM, Traverse JH, Henry TD et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54:2277–2286
Hu SL, Luo HS, Li JT et al (2010) Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells. Crit Care Med 38:2181–2189
Karussis D, Karageorgiou C, Vaknin-Dembinsky A et al (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 67:1187–1194
Liang J, Zhang H, Hua B et al (2010) Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 69:1423–1429
Tolar J, Le Blanc K, Keating A, Blazar BR (2010) Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells 28:1446–1455
Caplan AI (2009) Why are MSCs therapeutic? New data: new insight. J Pathol 217:318–324
Friedenstein AJ, Deriglasova UF, Kulagina NN et al (1974) Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 2:83–92
Nakahara H, Goldberg VM, Caplan AI (1991) Culture-expanded human periosteal-derived cells exhibit osteochondral potential in vivo. J Orthop Res 9:465–476
Lee JY, Qu-Petersen Z, Cao B et al (2000) Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J Cell Biol 150:1085–1100
Arai F, Ohneda O, Miyamoto T et al (2002) Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J Exp Med 195:1549–1563
Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228
Campagnoli C, Roberts IA, Kumar S et al (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98:2396–2402
In ’t Anker PS, Noort WA, Scherjon SA et al (2003) Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 88:845–852
In ’t Anker PS, Scherjon SA, Kleijburg-van der Keur C et al (2003) Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 102:1548–1549
Miao Z, Jin J, Chen L et al (2006) Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int 30:681–687
Lee OK, Kuo TK, Chen WM et al (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675
Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347
Caimi PF, Reese J, Lee Z, Lazarus HM (2010) Emerging therapeutic approaches for multipotent mesenchymal stromal cells. Curr Opin Hematol 17:505–513
Horwitz EM, Le Blanc K, Dominici M et al (2005) Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy 7:393–395
Rasmusson I, Ringden O, Sundberg B, Le Blanc K (2005) Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res 305:33–41
Le Blanc K, Tammik L, Sundberg B et al (2003) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 57:11–20
Ren G, Zhang L, Zhao X et al (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2:141–150
Polchert D, Sobinsky J, Douglas G et al (2008) IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol 38:1745–1755
Krampera M, Glennie S, Dyson J et al (2003) Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101:3722–3729
Jiang XX, Zhang Y, Liu B et al (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120–4126
Nauta AJ, Kruisselbrink AB, Lurvink E et al (2006) Mesenchymal stem cells inhibit generation and function of both CD34+−derived and monocyte-derived dendritic cells. J Immunol 177:2080–2087
Zhang B, Liu R, Shi D et al (2009) Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood 113:46–57
Spaggiari GM, Capobianco A, Abdelrazik H et al (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111:1327–1333
Asari S, Itakura S, Ferreri K et al (2009) Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol 37:604–615
Corcione A, Benvenuto F, Ferretti E et al (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107:367–372
Chabannes D, Hill M, Merieau E et al (2007) A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 110:3691–3694
Sundin M, Barrett AJ, Ringden O et al (2009) HSCT recipients have specific tolerance to MSC but not to the MSC donor. J Immunother 32:755–764
Majumdar MK, Keane-Moore M, Buyaner D et al (2003) Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 10:228–241
Le Blanc K, Tammik C, Rosendahl K et al (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890–896
Chan JL, Tang KC, Patel AP et al (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107:4817–4824
Parekkadan B, Milwid JM (2010) Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 12:87–117
English K, Ryan JM, Tobin L et al (2009) Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(high) forkhead box P3+ regulatory T cells. Clin Exp Immunol 156:149–160
Klyushnenkova E, Mosca JD, Zernetkina V et al (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12:47–57
Le Blanc K, Ringden O (2007) Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 262:509–525
Cohen JL, Sudres M (2009) A role for mesenchymal stem cells in the control of Âgraft-versus-host disease. Transplantation 87:S53–S54
Lazarus HM, Haynesworth SE, Gerson SL et al (1995) Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant 16:557–564
Koc ON, Gerson SL, Cooper BW et al (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 18:307–316
Frassoni F, Labopin M, Bacigalupo A et al (2002) Expanded mesenchymal stem cells (MSC) co-infused with HLA identical stem cell transplants, reduce acute and chronic graft versus host disease: a matched pair analysis. Bone Marrow Transplant 29:S2
Le Blanc K, Samuelsson H, Gustafsson B et al (2007) Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 21:1733–1738
Ball LM, Bernardo ME, Roelofs H et al (2007) 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 110:2764–2767
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 Transplant 43:447–454
Bernardo ME, Ball LM, Cometa AM et al (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 Transplant 46:200–207
Gonzalo-Daganzo R, Regidor C, Martin-Donaire T et al (2009) Results of a pilot study on the use of third-party donor mesenchymal stromal cells in cord blood transplantation in adults. Cytotherapy 11:278–288
Baron F, Lechanteur C, Willems E et al (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 Transplant 16:838–847
Schriber J, Agovi MA, Ho V et al (2010) Second unrelated donor hematopoietic cell transplantation for primary graft failure. Biol Blood Marrow Transplant 16:1099–1106
Fouillard L, Chapel A, Bories D et al (2007) Infusion of allogeneic-related HLA mismatched mesenchymal stem cells for the treatment of incomplete engraftment following autologous haematopoietic stem cell transplantation. Leukemia 21:568–570
Fang B, Li N, Song Y et al (2009) Cotransplantation of haploidentical mesenchymal stem cells to enhance engraftment of hematopoietic stem cells and to reduce the risk of graft failure in two children with severe aplastic anemia. Pediatr Transplant 13:499–502
Fang B, Song Y, Liao L et al (2007) Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. Transplant Proc 39:3358–3362
Fang B, Song Y, Zhao RC et al (2007) Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis. Transplant Proc 39:1710–1713
Meuleman N, Tondreau T, Ahmad I et al (2009) Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study. Stem Cells Dev 18:1247–1252
Sundin M, Orvell C, Rasmusson I et al (2006) Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual. Bone Marrow Transplant 37:1051–1059
Karlsson H, Samarasinghe S, Ball LM et al (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood 112:532–541
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Caimi, P.F., Lazarus, H.M. (2013). MSCs for Enhancement of Hematopoietic Progenitor Cell Engraftment and Poor Graft Function. In: Hematti, P., Keating, A. (eds) Mesenchymal Stromal Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5711-4_24
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DOI: https://doi.org/10.1007/978-1-4614-5711-4_24
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