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Published in:

01-01-2015

Bone marrow-derived mesenchymal stem cells for the treatment of heart failure

Authors: Takuya Narita, Ken Suzuki

Published in: Heart Failure Reviews | Issue 1/2015

Abstract

Heart failure remains a major cause of death and disability, requiring rapid development of new therapies. Bone marrow-derived mesenchymal stem cell (MSC)-based therapy is an emerging approach for the treatment of both acute and chronic heart failure. Following successful experimental studies in a range of models, more than 40 clinical trials of MSC-based therapy for heart failure have now been registered, and the results of completed clinical trials so far have shown feasibility and safety of this approach with therapeutic potential suggested (though preliminarily). However, there appear to be several critical issues to be solved before this treatment could become a widespread standard therapy for heart failure. In this review, we comprehensively and systemically summarize a total of 73 preclinical studies and 11 clinical trial reports published to date. By analyzing the data in these reports, (1) improvement in the cell delivery method to the heart in order to enhance donor cell engraftment, (2) elucidation of mechanisms underpinning the therapeutic effects of the treatment differentiation and/or treatment secretion, and (3) validation of the utility of allogeneic MSCs which could enhance the efficacy and expand the application/indication of this therapeutic approach are highlighted as future perspectives. These important respects are further discussed in this review article with referencing latest scientific and clinical information.

Liang CS, Delehanty JD (2009) Increasing post-myocardial infarction heart failure incidence in elderly patients a call for action. J Am Coll Cardiol 53:21–23PubMed

Frangogiannis NG, Smith CW, Entman ML (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53:31–47PubMed

Gordon O, Gilon D, He Z, May D, Lazarus A, Oppenheim A, Keshet E (2012) Vascular endothelial growth factor-induced neovascularization rescues cardiac function but not adverse remodeling at advanced ischemic heart disease. Arterioscler Thromb Vasc Biol 32:1642–1651PubMed

Sutton MG, Sharpe N (2000) Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101:2981–2988PubMed

Mosna F, Sensebe L, Krampera M (2010) Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev 19:1449–1470PubMed

Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI (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 16:557–564PubMed

Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ (2012) Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 7:e47559PubMedCentralPubMed

Imanishi Y, Saito A, Komoda H, Kitagawa-Sakakida S, Miyagawa S, Kondoh H, Ichikawa H, Sawa Y (2008) Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats. J Mol Cell Cardiol 44:662–671PubMed

Nagaya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y, Fujii T, Uematsu M, Ohgushi H, Yamagishi M, Tokudome T, Mori H, Miyatake K, Kitamura S (2005) Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112:1128–1135PubMed

10.

Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506PubMed

11.

Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403PubMed

12.

Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4:267–274PubMed

13.

Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247PubMed

14.

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMed

15.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMed

16.

Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, Fries JW, Tiemann K, Bohlen H, Hescheler J, Welz A, Bloch W, Jacobsen SE, Fleischmann BK (2007) Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110:1362–1369PubMed

17.

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 108:1340–1347PubMedCentralPubMed

18.

Miura M, Miura Y, Padilla-Nash HM, Molinolo AA, Fu B, Patel V, Seo BM, Sonoyama W, Zheng JJ, Baker CC, Chen W, Ried T, Shi S (2006) Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells 24:1095–1103PubMed

19.

Hatzistergos KE, Blum A, Ince T, Grichnik JM, Hare JM (2011) What is the oncologic risk of stem cell treatment for heart disease? Circ Res 108:1300–1303PubMedCentralPubMed

20.

Freyman T, Polin G, Osman H, Crary J, Lu M, Cheng L, Palasis M, Wilensky RL (2006) A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 27:1114–1122PubMed

21.

Elloumi-Hannachi I, Yamato M, Okano T (2010) Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med 267:54–70PubMed

22.

Yang J, Yamato M, Kohno C, Nishimoto A, Sekine H, Fukai F, Okano T (2005) Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials 26:6415–6422PubMed

23.

Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, Ogawa S (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:697–705PubMedCentralPubMed

24.

Noiseux N, Gnecchi M, Lopez-Ilasaca M, Zhang L, Solomon SD, Deb A, Dzau VJ, Pratt RE (2006) Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol Ther 14:840–850PubMed

25.

Griffin MD, Ritter T, Mahon BP (2010) Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther 21:1641–1655PubMed

26.

Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE (2004) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 94:678–685PubMed

27.

Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109:1543–1549PubMed

28.

Tang YL, Zhao Q, Qin X, Shen L, Cheng L, Ge J, Phillips MI (2005) Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg 80:229–236; discussion 236–227PubMed

29.

Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, Mazhari R, Boyle AJ, Zambrano JP, Rodriguez JE, Dulce R, Pattany PM, Valdes D, Revilla C, Heldman AW, McNiece I, Hare JM (2010) Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res 107:913–922PubMedCentralPubMed

30.

Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P (2005) Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci USA 102:8966–8971PubMedCentralPubMed

31.

http://clinicaltrials.gov/. (Accessed 20 Oct 2013)

32.

Heldman AW, DiFede DL, Fishman JE, Zambrano JP, Trachtenberg BH, Karantalis V, Mushtaq M, Williams AR, Suncion VY, McNiece IK, Ghersin E, Soto V, Lopera G, Miki R, Willens H, Hendel R, Mitrani R, Pattany P, Feigenbaum G, Oskouei B, Byrnes J, Lowery MH, Sierra J, Pujol MV, Delgado C, Gonzalez PJ, Rodriguez JE, Bagno LL, Rouy D, Altman P, Foo CW, da Silva J, Anderson E, Schwarz R, Mendizabal A, Hare JM (2014) Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC–HFT randomized trial. JAMA 311:62–73PubMed

33.

Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW (2012) Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308:2369–2379PubMed

34.

Bartunek J, Behfar A, Dolatabadi D, Vanderheyden M, Ostojic M, Dens J, El Nakadi B, Banovic M, Beleslin B, Vrolix M, Legrand V, Vrints C, Vanoverschelde JL, Crespo-Diaz R, Homsy C, Tendera M, Waldman S, Wijns W, Terzic A (2013) Cardiopoietic stem cell therapy in heart failure: the C-CURE (cardiopoietic stem cell therapy in heart failure) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol 61:2329–2338PubMed

35.

Lasala GP, Silva JA, Kusnick BA, Minguell JJ (2011) Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study. Cardiovasc Revasc Med 12:29–34PubMed

36.

Williams AR, Trachtenberg B, Velazquez DL, McNiece I, Altman P, Rouy D, Mendizabal AM, Pattany PM, Lopera GA, Fishman J, Zambrano JP, Heldman AW, Hare JM (2011) Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circ Res 108:792–796PubMedCentralPubMed

37.

Mohyeddin-Bonab M, Mohamad-Hassani MR, Alimoghaddam K, Sanatkar M, Gasemi M, Mirkhani H, Radmehr H, Salehi M, Eslami M, Farhig-Parsa A, Emami-Razavi H, Alemohammad MG, Solimani AA, Ghavamzadeh A, Nikbin B (2007) Autologous in vitro expanded mesenchymal stem cell therapy for human old myocardial infarction. Arch Iran Med 10:467–473PubMed

38.

Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, Zhang JJ, Chunhua RZ, Liao LM, Lin S, Sun JP (2004) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 94:92–95PubMed

39.

Gao LR, Pei XT, Ding QA, Chen Y, Zhang NK, Chen HY, Wang ZG, Wang YF, Zhu ZM, Li TC, Liu HL, Tong ZC, Yang Y, Nan X, Guo F, Shen JL, Shen YH, Zhang JJ, Fei YX, Xu HT, Wang LH, Tian HT, Liu DQ, Yang Y (2013) A critical challenge: dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction. Int J Cardiol 168:3191–3199PubMed

40.

Katritsis DG, Sotiropoulou PA, Karvouni E, Karabinos I, Korovesis S, Perez SA, Voridis EM, Papamichail M (2005) Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv 65:321–329PubMed

41.

Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, Denktas AE, Gammon RS, Hermiller JB Jr, Reisman MA, Schaer GL, Sherman W (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 54:2277–2286PubMedCentralPubMed

42.

Yang Z, Zhang F, Ma W, Chen B, Zhou F, Xu Z, Zhang Y, Zhang D, Zhu T, Wang L, Wang H, Ding Z, Zhang Y (2010) A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery. Cardiovasc Ther 28:380–385PubMed

43.

Tolar J, Le Blanc K, Keating A, Blazar BR (2010) Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells 28:1446–1455PubMedCentralPubMed

44.

Kang SK, Shin IS, Ko MS, Jo JY, Ra JC (2012) Journey of mesenchymal stem cells for homing: strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int 2012:342968PubMedCentralPubMed

45.

Ip JE, Wu Y, Huang J, Zhang L, Pratt RE, Dzau VJ (2007) Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for myocardial migration and engraftment. Mol Biol Cell 18:2873–2882PubMedCentralPubMed

46.

Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA, Leor J (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 108:863–868PubMed

47.

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

48.

Narita T, Shintani Y, Ikebe C, Kaneko M, Campbell NG, Coppen SR, Uppal R, Sawa Y, Yashiro K, Suzuki K (2013) The use of scaffold-free cell sheet technique to refine mesenchymal stromal cell-based therapy for heart failure. Mol Ther 21:860–867PubMedCentralPubMed

49.

Narita T, Shintani Y, Ikebe C, Kaneko M, Harada N, Tshuma N, Takahashi K, Campbell NG, Coppen SR, Yashiro K, Sawa Y, Suzuki K (2013) The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects. Int J Cardiol 168:261–269PubMed

50.

Huang HL, Hsing HW, Lai TC, Chen YW, Lee TR, Chan HT, Lyu PC, Wu CL, Lu YC, Lin ST, Lin CW, Lai CH, Chang HT, Chou HC, Chan HL (2010) Trypsin-induced proteome alteration during cell subculture in mammalian cells. J Biomed Sci 17:36PubMedCentralPubMed

51.

Fukushima S, Coppen SR, Lee J, Yamahara K, Felkin LE, Terracciano CM, Barton PJ, Yacoub MH, Suzuki K (2008) Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. PLoS One 3:e3071PubMedCentralPubMed

52.

Suzuki K, Murtuza B, Beauchamp JR, Brand NJ, Barton PJ, Varela-Carver A, Fukushima S, Coppen SR, Partridge TA, Yacoub MH (2004) Role of interleukin-1beta in acute inflammation and graft death after cell transplantation to the heart. Circulation 110:II219–II224PubMed

53.

Campbell NG, Suzuki K (2012) Cell delivery routes for stem cell therapy to the heart: current and future approaches. J Cardiovasc Transl Res 5:713–726PubMed

54.

Copland IB (2011) Mesenchymal stromal cells for cardiovascular disease. J Cardiovasc Dis Res 2:3–13PubMedCentralPubMed

55.

Ly HQ, Hoshino K, Pomerantseva I, Kawase Y, Yoneyama R, Takewa Y, Fortier A, Gibbs-Strauss SL, Vooght C, Frangioni JV, Hajjar RJ (2009) In vivo myocardial distribution of multipotent progenitor cells following intracoronary delivery in a swine model of myocardial infarction. Eur Heart J 30:2861–2868PubMedCentralPubMed

56.

Ruster B, Gottig S, Ludwig RJ, Bistrian R, Muller S, Seifried E, Gille J, Henschler R (2006) Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood 108:3938–3944PubMed

57.

Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363:783–784PubMed

58.

Fujita T, Sakaguchi T, Miyagawa S, Saito A, Sekiya N, Izutani H, Sawa Y (2011) Clinical impact of combined transplantation of autologous skeletal myoblasts and bone marrow mononuclear cells in patients with severely deteriorated ischemic cardiomyopathy. Surg Today 41:1029–1036PubMed

59.

Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93–98PubMed

60.

Chang SA, Lee EJ, Kang HJ, Zhang SY, Kim JH, Li L, Youn SW, Lee CS, Kim KH, Won JY, Sohn JW, Park KW, Cho HJ, Yang SE, Oh WI, Yang YS, Ho WK, Park YB, Kim HS (2008) Impact of myocardial infarct proteins and oscillating pressure on the differentiation of mesenchymal stem cells: effect of acute myocardial infarction on stem cell differentiation. Stem Cells 26:1901–1912PubMed

61.

Duan HF, Wu CT, Wu DL, Lu Y, Liu HJ, Ha XQ, Zhang QW, Wang H, Jia XX, Wang LS (2003) Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor. Mol Ther 8:467–474PubMed

62.

Hahn JY, Cho HJ, Kang HJ, Kim TS, Kim MH, Chung JH, Bae JW, Oh BH, Park YB, Kim HS (2008) Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J Am Coll Cardiol 51:933–943PubMed

63.

Wang T, Xu Z, Jiang W, Ma A (2006) Cell-to-cell contact induces mesenchymal stem cell to differentiate into cardiomyocyte and smooth muscle cell. Int J Cardiol 109:74–81PubMed

64.

Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C (2004) Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22:377–384PubMed

65.

Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156PubMed

66.

Burchfield JS, Iwasaki M, Koyanagi M, Urbich C, Rosenthal N, Zeiher AM, Dimmeler S (2008) Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction. Circ Res 103:203–211PubMed

67.

Guo J, Lin GS, Bao CY, Hu ZM, Hu MY (2007) Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction. Inflammation 30:97–104PubMed

68.

Tsuda T, Gao E, Evangelisti L, Markova D, Ma X, Chu ML (2003) Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes. Cardiovasc Res 59:926–933PubMed

69.

Molina EJ, Palma J, Gupta D, Torres D, Gaughan JP, Houser S, Macha M (2009) Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy. J Tissue Eng Regen Med 3:85–91PubMed

70.

Krijnen PA, Nijmeijer R, Meijer CJ, Visser CA, Hack CE, Niessen HW (2002) Apoptosis in myocardial ischaemia and infarction. J Clin Pathol 55:801–811PubMedCentralPubMed

71.

Afzal MR, Haider H, Idris NM, Jiang S, Ahmed RP, Ashraf M (2010) Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-kappaB signaling. Antioxid Redox Signal 12:693–702PubMedCentralPubMed

72.

Isele NB, Lee HS, Landshamer S, Straube A, Padovan CS, Plesnila N, Culmsee C (2007) Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons. Neurochem Int 50:243–250PubMed

73.

Tsubokawa T, Yagi K, Nakanishi C, Zuka M, Nohara A, Ino H, Fujino N, Konno T, Kawashiri MA, Ishibashi-Ueda H, Nagaya N, Yamagishi M (2008) Impact of anti-apoptotic and anti-oxidative effects of bone marrow mesenchymal stem cells with transient overexpression of heme oxygenase-1 on myocardial ischemia. Am J Physiol Heart Circ Physiol 298:H1320–H1329

74.

Fossett E, Khan WS (2012) Optimising human mesenchymal stem cell numbers for clinical application: a literature review. Stem Cells Int 2012:465259PubMedCentralPubMed

75.

Drexler HG, Uphoff CC (2002) Mycoplasma contamination of cell cultures: incidence, sources, effects, detection, elimination, prevention. Cytotechnology 39:75–90PubMedCentralPubMed

76.

Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, Li RK (2010) Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation 122:2419–2429PubMed

77.

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 75:389–397PubMed

78.

Dazzi F, Lopes L, Weng L (2012) Mesenchymal stromal cells: a key player in ‘innate tolerance’? Immunology 137:206–213PubMedCentralPubMed

79.

Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105:2821–2827PubMed

80.

Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107:367–372PubMed

81.

Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L (2006) 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 107:1484–1490PubMed

82.

Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC (2009) Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood 113:46–57PubMed

83.

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, Ringden O (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586PubMed

84.

Fotino C, Ricordi C, Lauriola V, Alejandro R, Pileggi A (2010) Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes. Rev Diabet Stud 7:144–157PubMedCentralPubMed

85.

Amado LC, Saliaris AP, Schuleri KH, St John M, Xie JS, Cattaneo S, Durand DJ, Fitton T, Kuang JQ, Stewart G, Lehrke S, Baumgartner WW, Martin BJ, Heldman AW, Hare JM (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci USA 102:11474–11479PubMedCentralPubMed

86.

Quevedo HC, Hatzistergos KE, Oskouei BN, Feigenbaum GS, Rodriguez JE, Valdes D, Pattany PM, Zambrano JP, Hu Q, McNiece I, Heldman AW, Hare JM (2009) Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci USA 106:14022–14027PubMedCentralPubMed

87.

Hashemi SM, Ghods S, Kolodgie FD, Parcham-Azad K, Keane M, Hamamdzic D, Young R, Rippy MK, Virmani R, Litt H, Wilensky RL (2008) A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction. Eur Heart J 29:251–259PubMed

88.

Foudah D, Redaelli S, Donzelli E, Bentivegna A, Miloso M, Dalpra L, Tredici G (2009) Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells. Chromosome Res 17:1025–1039PubMedCentralPubMed

89.

Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY (2010) A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28:1099–1106PubMed

90.

Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang JA, Wei L (2008) Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 135:799–808PubMed

91.

Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, Dzau VJ (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9:1195–1201PubMed

92.

Boomsma RA, Swaminathan PD, Geenen DL (2007) Intravenously injected mesenchymal stem cells home to viable myocardium after coronary occlusion and preserve systolic function without altering infarct size. Int J Cardiol 122:17–28PubMed

93.

Van Linthout S, Savvatis K, Miteva K, Peng J, Ringe J, Warstat K, Schmidt-Lucke C, Sittinger M, Schultheiss HP, Tschope C (2011) Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis. Eur Heart J 32:2168–2178PubMedCentralPubMed

94.

van der Bogt KE, Sheikh AY, Schrepfer S, Hoyt G, Cao F, Ransohoff KJ, Swijnenburg RJ, Pearl J, Lee A, Fischbein M, Contag CH, Robbins RC, Wu JC (2008) Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation 118:S121–S129PubMedCentralPubMed

95.

van der Bogt KE, Schrepfer S, Yu J, Sheikh AY, Hoyt G, Govaert JA, Velotta JB, Contag CH, Robbins RC, Wu JC (2009) Comparison of transplantation of adipose tissue- and bone marrow-derived mesenchymal stem cells in the infarcted heart. Transplantation 87:642–652PubMedCentralPubMed

96.

Cho J, Zhai P, Maejima Y, Sadoshima J (2011) Myocardial injection with GSK-3beta-overexpressing bone marrow-derived mesenchymal stem cells attenuates cardiac dysfunction after myocardial infarction. Circ Res 108:478–489PubMedCentralPubMed

97.

Buccini S, Haider KH, Ahmed RP, Jiang S, Ashraf M (2012) Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. Basic Res Cardiol 107:301PubMedCentralPubMed

98.

Grauss RW, Winter EM, van Tuyn J, Pijnappels DA, Steijn RV, Hogers B, van der Geest RJ, de Vries AA, Steendijk P, van der Laarse A, Gittenberger-de Groot AC, Schalij MJ, Atsma DE (2007) Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction. Am J Physiol Heart Circ Physiol 293:H2438–H2447PubMed

99.

Li TS, Cheng K, Malliaras K, Smith RR, Zhang Y, Sun B, Matsushita N, Blusztajn A, Terrovitis J, Kusuoka H, Marban L, Marban E (2012) Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol 59:942–953PubMedCentralPubMed

100.

Derval N, Barandon L, Dufourcq P, Leroux L, Lamaziere JM, Daret D, Couffinhal T, Duplaa C (2008) Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model. Eur J Cardiothorac Surg 34:248–254PubMed

101.

Mills WR, Mal N, Kiedrowski MJ, Unger R, Forudi F, Popovic ZB, Penn MS, Laurita KR (2007) Stem cell therapy enhances electrical viability in myocardial infarction. J Mol Cell Cardiol 42:304–314PubMed

102.

Ohnishi S, Yanagawa B, Tanaka K, Miyahara Y, Obata H, Kataoka M, Kodama M, Ishibashi-Ueda H, Kangawa K, Kitamura S, Nagaya N (2007) Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J Mol Cell Cardiol 42:88–97PubMed

103.

Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, Yamagishi M, Mori H, Kangawa K, Kitamura S (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287:H2670–H2676PubMed

104.

Li Y, Yao Y, Sheng Z, Yang Y, Ma G (2011) Dual-modal tracking of transplanted mesenchymal stem cells after myocardial infarction. Int J Nanomed 6:815–823

105.

Lopez Y, Lutjemeier B, Seshareddy K, Trevino EM, Hageman KS, Musch TI, Borgarelli M, Weiss ML (2013) Wharton’s jelly or bone marrow mesenchymal stromal cells improve cardiac function following myocardial infarction for more than 32 weeks in a rat model: a preliminary report. Curr Stem Cell Res Ther 8:46–59PubMed

106.

Wang T, Tang W, Sun S, Wan Z, Xu T, Huang Z, Weil MH (2009) Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats. J Mol Cell Cardiol 46:378–384PubMed

107.

Khan M, Meduru S, Mohan IK, Kuppusamy ML, Wisel S, Kulkarni A, Rivera BK, Hamlin RL, Kuppusamy P (2009) Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart. J Mol Cell Cardiol 47:275–287PubMedCentralPubMed

108.

Jiang S, Haider H, Idris NM, Salim A, Ashraf M (2006) Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ Res 99:776–784PubMed

109.

Tang J, Xie Q, Pan G, Wang J, Wang M (2006) Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg 30:353–361PubMed

110.

Jiang S, Kh Haider H, Ahmed RP, Idris NM, Salim A, Ashraf M (2008) Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium. J Mol Cell Cardiol 44:582–596PubMedCentralPubMed

111.

Davani S, Marandin A, Mersin N, Royer B, Kantelip B, Herve P, Etievent JP, Kantelip JP (2003) Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation 108(Suppl. 1):II253–II258PubMed

112.

Furlani D, Li W, Pittermann E, Klopsch C, Wang L, Knopp A, Jungebluth P, Thedinga E, Havenstein C, Westien I, Ugurlucan M, Li RK, Ma N, Steinhoff G (2009) A transformed cell population derived from cultured mesenchymal stem cells has no functional effect after transplantation into the injured heart. Cell Transplant 18:319–331PubMed

113.

Al Kindi AH, Asenjo JF, Ge Y, Chen GY, Bhathena J, Chiu RC, Prakash S, Shum-Tim D (2011) Microencapsulation to reduce mechanical loss of microspheres: implications in myocardial cell therapy. Eur J Cardiothorac Surg 39:241–247PubMed

114.

Wang W, Jin P, Wang L, Yang Z, Hu S, Gao B, Zhang H (2010) Impact of escaped bone marrow mesenchymal stromal cells on extracardiac organs after intramyocardial implantation in a rat myocardial infarction model. Cell Transplant 19:1599–1607PubMed

115.

Zeng B, Chen H, Zhu C, Ren X, Lin G, Cao F (2008) Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance. Eur J Cardiothorac Surg 34:850–856PubMed

116.

Dai W, Hale SL, Martin BJ, Kuang JQ, Dow JS, Wold LE, Kloner RA (2005) Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 112:214–223PubMed

117.

Guarita-Souza LC, Carvalho KA, Rebelatto C, Senegaglia A, Hansen P, Furuta M, Miyague N, Francisco JC, Olandoski M, Faria-Neto JR, Oliveira SA, Brofman PR (2006) Cell transplantation: differential effects of myoblasts and mesenchymal stem cells. Int J Cardiol 111:423–429PubMed

118.

Amsalem Y, Mardor Y, Feinberg MS, Landa N, Miller L, Daniels D, Ocherashvilli A, Holbova R, Yosef O, Barbash IM, Leor J (2007) Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation 116:I38–I45PubMed

119.

Gao LR, Zhang NK, Bai J, Ding QA, Wang ZG, Zhu ZM, Fei YX, Yang Y, Xu RY, Chen Y (2010) The apelin-APJ pathway exists in cardiomyogenic cells derived from mesenchymal stem cells in vitro and in vivo. Cell Transplant 19:949–958PubMed

120.

Wang A, Shen F, Liang Y, Wang J (2011) Marrow-derived MSCs and atorvastatin improve cardiac function in rat model of AMI. Int J Cardiol 150:28–32PubMed

121.

Flynn A, Chen X, O’Connell E, O’Brien T (2012) A comparison of the efficacy of transplantation of bone marrow-derived mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute myocardial infarction. Stem Cell Res Ther 3:36PubMedCentralPubMed

122.

Wang T, Sun S, Wan Z, Weil MH, Tang W (2012) Effects of bone marrow mesenchymal stem cells in a rat model of myocardial infarction. Resuscitation 83:1391–1396PubMed

123.

Enoki C, Otani H, Sato D, Okada T, Hattori R, Imamura H (2010) Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction. Int J Cardiol 138:9–18PubMed

124.

Hou M, Yang KM, Zhang H, Zhu WQ, Duan FJ, Wang H, Song YH, Wei YJ, Hu SS (2007) Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats. Int J Cardiol 115:220–228PubMed

125.

Wang M, Tan J, Wang Y, Meldrum KK, Dinarello CA, Meldrum DR (2009) IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction. Proc Natl Acad Sci USA 106:17499–17504PubMedCentralPubMed

126.

Bayes-Genis A, Soler-Botija C, Farre J, Sepulveda P, Raya A, Roura S, Prat-Vidal C, Galvez-Monton C, Montero JA, Buscher D, Izpisua Belmonte JC (2010) Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. J Mol Cell Cardiol 49:771–780PubMed

127.

Arminan A, Gandia C, Garcia-Verdugo JM, Lledo E, Trigueros C, Ruiz-Sauri A, Minana MD, Solves P, Paya R, Montero JA, Sepulveda P (2010) Mesenchymal stem cells provide better results than hematopoietic precursors for the treatment of myocardial infarction. J Am Coll Cardiol 55:2244–2253PubMed

128.

Herrmann JL, Abarbanell AM, Wang Y, Weil BR, Poynter JA, Manukyan MC, Meldrum DR (2011) Transforming growth factor-alpha enhances stem cell-mediated postischemic myocardial protection. Ann Thorac Surg 92:1719–1725PubMed

129.

Rasmussen JG, Frobert O, Holst-Hansen C, Kastrup J, Baandrup U, Zachar V, Fink T, Simonsen U (2012) Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model. Cell Transplant 23:195–206

130.

Molina EJ, Palma J, Gupta D, Torres D, Gaughan JP, Houser S, Macha M (2008) Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy. J Thorac Cardiovasc Surg 135:292–299PubMed

131.

Mokashi SA, Guan J, Wang D, Tchantchaleishvili V, Brigham M, Lipsitz S, Lee LS, Schmitto JD, Bolman RM 3rd, Khademhosseini A, Liao R, Chen FY (2010) Preventing cardiac remodeling: the combination of cell-based therapy and cardiac support therapy preserves left ventricular function in rodent model of myocardial ischemia. J Thorac Cardiovasc Surg 140:1374–1380PubMed

132.

Kang K, Sun L, Xiao Y, Li SH, Wu J, Guo J, Jiang SL, Yang L, Yau TM, Weisel RD, Radisic M, Li RK (2012) Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration. J Am Coll Cardiol 60:2237–2249PubMed

133.

Xu YL, Gao YH, Liu Z, Tan KB, Hua X, Fang ZQ, Wang YL, Wang YJ, Xia HM, Zhuo ZX (2010) Myocardium-targeted transplantation of mesenchymal stem cells by diagnostic ultrasound-mediated microbubble destruction improves cardiac function in myocardial infarction of New Zealand rabbits. Int J Cardiol 138:182–195PubMed

134.

Price MJ, Chou CC, Frantzen M, Miyamoto T, Kar S, Lee S, Shah PK, Martin BJ, Lill M, Forrester JS, Chen PS, Makkar RR (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 111:231–239PubMed

135.

Halkos ME, Zhao ZQ, Kerendi F, Wang NP, Jiang R, Schmarkey LS, Martin BJ, Quyyumi AA, Few WL, Kin H, Guyton RA, Vinten-Johansen J (2008) Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction. Basic Res Cardiol 103:525–536PubMed

136.

Schuleri KH, Centola M, Choi SH, Evers KS, Dawoud F, George RT, Lima JA, Lardo AC (2011) Multi-detector computed tomography for evaluation of myocardial cell therapy in heart failure: a comparison with CMR imaging. JACC Cardiovasc Imaging 4:1284–1293PubMedCentralPubMed

137.

Yang YJ, Qian HY, Huang J, Geng YJ, Gao RL, Dou KF, Yang GS, Li JJ, Shen R, He ZX, Lu MJ, Zhao SH (2008) Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts. Eur Heart J 29:1578–1590PubMed

138.

Huang SD, Lu FL, Xu XY, Liu XH, Zhao XX, Zhao BZ, Wang L, Gong DJ, Yuan Y, Xu ZY (2006) Transplantation of angiogenin-overexpressing mesenchymal stem cells synergistically augments cardiac function in a porcine model of chronic ischemia. J Thorac Cardiovasc Surg 132:1329–1338PubMed

139.

Schuleri KH, Feigenbaum GS, Centola M, Weiss ES, Zimmet JM, Turney J, Kellner J, Zviman MM, Hatzistergos KE, Detrick B, Conte JV, McNiece I, Steenbergen C, Lardo AC, Hare JM (2009) Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J 30:2722–2732PubMedCentralPubMed

140.

Wang X, Jameel MN, Li Q, Mansoor A, Qiang X, Swingen C, Panetta C, Zhang J (2009) Stem cells for myocardial repair with use of a transarterial catheter. Circulation 120:S238–S246PubMedCentralPubMed

141.

Amado LC, Schuleri KH, Saliaris AP, Boyle AJ, Helm R, Oskouei B, Centola M, Eneboe V, Young R, Lima JA, Lardo AC, Heldman AW, Hare JM (2006) Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol 48:2116–2124PubMed

142.

Schuleri KH, Amado LC, Boyle AJ, Centola M, Saliaris AP, Gutman MR, Hatzistergos KE, Oskouei BN, Zimmet JM, Young RG, Heldman AW, Lardo AC, Hare JM (2008) Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. Am J Physiol Heart Circ Physiol 294:H2002–H2011PubMed

143.

Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, Morales AR, Da Silva J, Sussman MA, Heldman AW, Hare JM (2013) Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation 127:213–223PubMedCentralPubMed

144.

Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E (2007) Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J 28:2667–2677PubMed

145.

Peng C, Yang K, Xiang P, Zhang C, Zou L, Wu X, Gao Y, Kang Z, He K, Liu J, Cheng M, Wang J, Chen L (2013) Effect of transplantation with autologous bone marrow stem cells on acute myocardial infarction. Int J Cardiol 162:158–165PubMed

146.

Dubois C, Liu X, Claus P, Marsboom G, Pokreisz P, Vandenwijngaert S, Depelteau H, Streb W, Chaothawee L, Maes F, Gheysens O, Debyser Z, Gillijns H, Pellens M, Vandendriessche T, Chuah M, Collen D, Verbeken E, Belmans A, Van de Werf F, Bogaert J, Janssens S (2010) Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction. J Am Coll Cardiol 55:2232–2243PubMed

147.

Dixon JA, Gorman RC, Stroud RE, Bouges S, Hirotsugu H, Gorman JH 3rd, Martens TP, Itescu S, Schuster MD, Plappert T, St John-Sutton MG, Spinale FG (2009) Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction. Circulation 120:S220–S229PubMedCentralPubMed

148.

Houtgraaf JH, de Jong R, Kazemi K, de Groot D, van der Spoel TI, Arslan F, Hoefer I, Pasterkamp G, Itescu S, Zijlstra F, Geleijnse ML, Serruys PW, Duckers HJ (2013) Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res 113:153–166PubMed

149.

Perin EC, Silva GV, Assad JA, Vela D, Buja LM, Sousa AL, Litovsky S, Lin J, Vaughn WK, Coulter S, Fernandes MR, Willerson JT (2008) Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 44:486–495PubMed

Title: Bone marrow-derived mesenchymal stem cells for the treatment of heart failure
Authors: Takuya Narita
Ken Suzuki
Publication date: 01-01-2015
Publisher: Springer US
Published in: Heart Failure Reviews / Issue 1/2015
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-014-9435-x

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