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Progress and prospects: Cell based regenerative therapy for cardiovascular disease

Gene Therapy volume 13, pages 659–671 (2006)Cite this article

Abstract

Experimental and clinical studies are progressing simultaneously to investigate the mechanisms and efficacy of progenitor cell treatment after an acute myocardial infarction and in chronic congestive heart failure. Multipotent progenitor cells appear to be capable of improving cardiac perfusion and/or function; however, the mechanisms still are unclear, and the issue of whether or not trans-differentiation occurs remains unsettled. Both experimentally and clinically, cells originating from different tissues have been shown capable of restoring cardiac function, but more recently multiple groups have identified resident cardiac progenitor cells that seem to participate in regenerating the heart after injury. Clinically, cells originating from blood or bone marrow have been proven to be safe whereas injection of skeletal myoblasts has been associated with the occurrence of ventricular arrhythmias. Myoblasts can transform into rapidly beating myotubes; however, thus far convincing evidence for electro-mechanical coupling between myoblasts and cardiomyocytes is lacking. Moving forward, mechanistic studies will benefit from the use of genetic markers and Cre/lox reporter systems that are less prone to misinterpretation than fluorescent antibodies, and a more convincing answer regarding therapeutic efficacy will come from adequately powered randomized placebo controlled trials.

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References

  1. Toh R, Kawashima S, Kawai M, Sakoda T, Ueyama T, Satomi-Kobayashi S et al. Transplantation of cardiotrophin-1-expressing myoblasts to the left ventricular wall alleviates the transition from compensatory hypertrophy to congestive heart failure in Dahl salt-sensitive hypertensive rats. J Am Coll Cardiol 2004; 43: 2337–2347.

    CAS  PubMed  Google Scholar 

  2. Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z . Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 2003; 108: 2070–2073.

    PubMed  Google Scholar 

  3. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002; 106: 3009–3017.

    PubMed  Google Scholar 

  4. Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP . Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003; 361: 47–49.

    PubMed  Google Scholar 

  5. Fernandez-Aviles F, San Roman JA, Garcia-Frade J, Fernandez ME, Penarrubia MJ, de la Fuente L et al. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 2004; 95: 742–748.

    CAS  PubMed  Google Scholar 

  6. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004; 364: 141–148.

    PubMed  Google Scholar 

  7. Menasche P, Hagege AA, Vilquin JT, Desnos M, Abergel E, Pouzet B et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003; 41: 1078–1083.

    PubMed  Google Scholar 

  8. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003; 107: 2294–2302.

    PubMed  Google Scholar 

  9. Badorff C, Brandes RP, Popp R, Rupp S, Urbich C, Aicher A et al. Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation 2003; 107: 1024–1032.

    PubMed  Google Scholar 

  10. Deb A, Wang S, Skelding KA, Miller D, Simper D, Caplice NM . Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation 2003; 107: 1247–1249.

    PubMed  Google Scholar 

  11. Kajstura J, Rota M, Whang B, Cascapera S, Hosoda T, Bearzi C et al. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 2005; 96: 127–137.

    CAS  PubMed  Google Scholar 

  12. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC . Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004; 428: 668–673.

    CAS  PubMed  Google Scholar 

  13. Castro RF, Jackson KA, Goodell MA, Robertson CS, Liu H, Shine HD . Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science 2002; 297: 1299.

    CAS  PubMed  Google Scholar 

  14. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL . Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 297: 2256–2259.

    CAS  PubMed  Google Scholar 

  15. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004; 428: 664–668.

    CAS  PubMed  Google Scholar 

  16. Jiang S, Walker L, Afentoulis M, Anderson DA, Jauron-Mills L, Corless CL et al. Transplanted human bone marrow contributes to vascular endothelium. Proc Natl Acad Sci USA 2004; 101: 16891–16896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Reinecke H, Minami E, Poppa V, Murry CE . Evidence for fusion between cardiac and skeletal muscle cells. Circ Res 2004; 94: e56–e60.

    CAS  PubMed  Google Scholar 

  18. Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 2004; 10: 494–501.

    CAS  PubMed  Google Scholar 

  19. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 2002; 416: 542–545.

    CAS  PubMed  Google Scholar 

  20. Koyanagi M, Brandes RP, Haendeler J, Zeiher AM, Dimmeler S . Cell-to-cell connection of endothelial progenitor cells with cardiac myocytes by nanotubes: a novel mechanism for cell fate changes? Circ Res 2005; 96: 1039–1041.

    CAS  PubMed  Google Scholar 

  21. Rubart M, Soonpaa MH, Nakajima H, Field LJ . Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation. J Clin Invest 2004; 114: 775–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S . Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci USA 2003; 100: 7808–7811.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Rehman J, Li J, Orschell CM, March KL . Peripheral blood ‘endothelial progenitor cells’ are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 2003; 107: 1164–1169.

    PubMed  Google Scholar 

  24. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109: 1543–1549.

    CAS  PubMed  Google Scholar 

  25. Kinnaird T, Stabile E, Burnett MS, Epstein SE . Bone marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences. Circ Res 2004; 95: 354–363.

    CAS  PubMed  Google Scholar 

  26. Yoon CH, Hur J, Park KW, Kim JH, Lee CS, Oh IY et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation 2005; 112: 1618–1627.

    PubMed  Google Scholar 

  27. Kupatt C, Horstkotte J, Vlastos GA, Pfosser A, Lebherz C, Semisch M et al. Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J 2005; 19: 1576–1578.

    CAS  PubMed  Google Scholar 

  28. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005; 11: 367–368.

    CAS  PubMed  Google Scholar 

  29. Kermani P, Rafii D, Jin DK, Whitlock P, Schaffer W, Chiang A et al. Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors. J Clin Invest 2005; 115: 653–663.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Rafii S, Lyden D . Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 2003; 9: 702–712.

    CAS  PubMed  Google Scholar 

  31. Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111: 2981–2987.

    PubMed  Google Scholar 

  32. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353: 999–1007.

    CAS  PubMed  Google Scholar 

  33. Rafii S, Lyden D, Benezra R, Hattori K, Heissig B . Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2002; 2: 826–835.

    CAS  PubMed  Google Scholar 

  34. Urbich C, Heeschen C, Aicher A, Dernbach E, Zeiher AM, Dimmeler S . Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells. Circulation 2003; 108: 2511–2516.

    PubMed  Google Scholar 

  35. Handgretinger R, Gordon PR, Leimig T, Chen X, Buhring HJ, Niethammer D et al. Biology and plasticity of CD133+ hematopoietic stem cells. Ann NY Acad Sci 2003; 996: 141–151.

    CAS  PubMed  Google Scholar 

  36. Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J et al. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 2003; 108: 2212–2218.

    CAS  PubMed  Google Scholar 

  37. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106: 1913–1918.

    PubMed  Google Scholar 

  38. Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial (see comment). Lancet 2004; 363: 751–756.

    CAS  PubMed  Google Scholar 

  39. Romagnani P, Annunziato F, Liotta F, Lazzeri E, Mazzinghi B, Frosali F et al. CD14+CD34low cells with stem cell phenotypic and functional features are the major source of circulating endothelial progenitors. Circ Res 2005; 97: 314–322.

    CAS  PubMed  Google Scholar 

  40. Liadaki K, Kho AT, Sanoudou D, Schienda J, Flint A, Beggs AH et al. Side population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers. Exp Cell Res 2005; 303: 360–374.

    CAS  PubMed  Google Scholar 

  41. Ueda T, Brenner S, Malech HL, Langemeijer SM, Perl S, Kirby M et al. Cloning and functional analysis of the rhesus macaque ABCG2 gene. Forced expression confers an SP phenotype among hematopoietic stem cell progeny in vivo. J Biol Chem 2005; 280: 991–998.

    CAS  PubMed  Google Scholar 

  42. Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 2004; 265: 262–275.

    CAS  PubMed  Google Scholar 

  43. Pfister O, Mouquet F, Jain M, Summer R, Helmes M, Fine A et al. CD31− but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res 2005; 97: 52–61.

    CAS  PubMed  Google Scholar 

  44. Rangappa S, Entwistle JW, Wechsler AS, Kresh JY . Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype. J Thorac Cardiovasc Surg 2003; 126: 124–132.

    CAS  PubMed  Google Scholar 

  45. Xu W, Zhang X, Qian H, Zhu W, Sun X, Hu J et al. Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro. Exp Biol Med (Maywood) 2004; 229: 623–631.

    CAS  Google Scholar 

  46. Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003; 108: 863–868.

    PubMed  Google Scholar 

  47. Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z et al. Allogeneic bone marrow-derived flk-1+Sca-1-mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance. Exp Hematol 2004; 32: 861–867.

    CAS  PubMed  Google Scholar 

  48. Jorgensen C, Djouad F, Apparailly F, Noel D . Engineering mesenchymal stem cells for immunotherapy. Gene Therapy 2003; 10: 928–931.

    CAS  PubMed  Google Scholar 

  49. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30: 42–48.

    PubMed  Google Scholar 

  50. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99: 3838–3843.

    CAS  PubMed  Google Scholar 

  51. Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K et al. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 2005; 115: 326–338.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763–776.

    CAS  PubMed  Google Scholar 

  53. Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S et al. Nkx2–5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 2004; 117: 373–386.

    CAS  PubMed  Google Scholar 

  54. Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 2003; 100: 12313–12318.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA 2005; 102: 8692–8697.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 2005; 97: 663–673.

    CAS  PubMed  Google Scholar 

  57. Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci USA 2005; 102: 8966–8971.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 2005; 433: 647–653.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 2004; 95: 911–921.

    CAS  PubMed  Google Scholar 

  60. Murtuza B, Suzuki K, Bou-Gharios G, Beauchamp JR, Smolenski RT, Partridge TA et al. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci USA 2004; 101: 4216–4221.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Pouly J, Hagege AA, Vilquin JT, Bissery A, Rouche A, Bruneval P et al. Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy? Circulation 2004; 110: 1626–1631.

    PubMed  Google Scholar 

  62. Ghostine S, Carrion C, Souza LC, Richard P, Bruneval P, Vilquin JT et al. Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation 2002; 106: I131–I136.

    PubMed  Google Scholar 

  63. Cousin B, Andre M, Arnaud E, Penicaud L, Casteilla L . Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun 2003; 301: 1016–1022.

    CAS  PubMed  Google Scholar 

  64. Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R et al. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 2004; 109: 656–663.

    PubMed  Google Scholar 

  65. Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A . Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 2004; 110: 349–355.

    CAS  PubMed  Google Scholar 

  66. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 2004; 109: 1292–1298.

    PubMed  Google Scholar 

  67. Fraidenraich D, Stillwell E, Romero E, Wilkes D, Manova K, Basson CT et al. Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells. Science 2004; 306: 247–252.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Hodgson DM, Behfar A, Zingman LV, Kane GC, Perez-Terzic C, Alekseev AE et al. Stable benefit of embryonic stem cell therapy in myocardial infarction. Am J Physiol Heart Circ Physiol 2004; 287: H471–H479.

    CAS  PubMed  Google Scholar 

  69. Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, Koo JM et al. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 2004; 303: 1669–1674.

    CAS  PubMed  Google Scholar 

  70. Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzezniczak J, Rozwadowska N et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J 2004; 148: 531–537.

    PubMed  Google Scholar 

  71. Pagani FD, DerSimonian H, Zawadzka A, Wetzel K, Edge AS, Jacoby DB et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol 2003; 41: 879–888.

    PubMed  Google Scholar 

  72. Smits PC, van Geuns RJ, Poldermans D, Bountioukos M, Onderwater EE, Lee CH et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol 2003; 42: 2063–2069.

    PubMed  Google Scholar 

  73. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 2004; 110: II213–II218.

    PubMed  Google Scholar 

  74. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004; 44: 1690–1699.

    PubMed  Google Scholar 

  75. Janssens S . Intracoronary autologous bone-marrow cell transfer after myocardial infarction. ACC Annual Scientific Sessions 2005, Orlando, FL 2005.

  76. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion. First randomized and placebo-controlled study. Circ Res 2005; 97: 756–762.

    CAS  PubMed  Google Scholar 

  77. Kizana E, Ginn SL, Allen DG, Ross DL, Alexander IE . Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling. Circulation 2005; 111: 394–398.

    PubMed  Google Scholar 

  78. Li TS, Hayashi M, Ito H, Furutani A, Murata T, Matsuzaki M et al. Regeneration of infarcted myocardium by intramyocardial implantation of ex vivo transforming growth factor-beta-preprogrammed bone marrow stem cells. Circulation 2005; 111: 2438–2445.

    CAS  PubMed  Google Scholar 

  79. Davis ME, Hsieh PC, Grodzinsky AJ, Lee RT . Custom design of the cardiac microenvironment with biomaterials. Circ Res 2005; 97: 8–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Davis ME, Motion JP, Narmoneva DA, Takahashi T, Hakuno D, Kamm RD et al. Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation 2005; 111: 442–450.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Leor J, Amsalem Y, Cohen S . Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Ther 2005; 105: 151–163.

    CAS  PubMed  Google Scholar 

  82. Gojo S, Gojo N, Takeda Y, Mori T, Abe H, Kyo S et al. In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells. Exp Cell Res 2003; 288: 51–59.

    CAS  PubMed  Google Scholar 

  83. Xaymardan M, Tang L, Zagreda L, Pallante B, Zheng J, Chazen JL et al. Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes. Circ Res 2004; 94: E39–E45.

    CAS  PubMed  Google Scholar 

  84. Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003; 107: 2134–2139.

    PubMed  Google Scholar 

  85. Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C et al. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 2003; 107: 461–468.

    PubMed  Google Scholar 

  86. Agbulut O, Vandervelde S, Al Attar N, Larghero J, Ghostine S, Leobon B et al. Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium. [see comment]. J Am Coll Cardiol 2004; 44: 458–463.

    CAS  PubMed  Google Scholar 

  87. Askari A, Unzek S, Goldman CK, Ellis SG, Thomas JD, DiCorleto PE et al. Cellular, but not direct, adenoviral delivery of vascular endothelial growth factor results in improved left ventricular function and neovascularization in dilated ischemic cardiomyopathy. J Am Coll Cardiol 2004; 43: 1908–1914.

    CAS  PubMed  Google Scholar 

  88. Thompson RB, Emani SM, Davis BH, van den Bos EJ, Morimoto Y, Craig D et al. Comparison of intracardiac cell transplantation: autologous skeletal myoblasts versus bone marrow cells. Circulation 2003; 108 (Suppl 1): II264–II271.

    PubMed  Google Scholar 

  89. Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 2003; 361: 45–46.

    PubMed  Google Scholar 

  90. Li TS, Hamano K, Hirata K, Kobayashi T, Nishida M . The safety and feasibility of the local implantation of autologous bone marrow cells for ischemic heart disease. J Cardiac Surg 2003; 18: S69–S75.

    Google Scholar 

  91. Dib N, McCarthy P, Campbell A, Yeager M, Pagani FD, Wright S et al. Feasibilty and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy: long term follow-up. ACC Annual Scientific Session 2005, Orlando, FL 2005.

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  1. Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    E D de Muinck

  2. Department of Medicine, Angiogenesis Research Center and Section of Cardiology, Lebanon, NH, USA

    C Thompson

  3. Department of Pharmacology and Toxicology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    M Simons

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de Muinck, E., Thompson, C. & Simons, M. Progress and prospects: Cell based regenerative therapy for cardiovascular disease. Gene Ther 13, 659–671 (2006). https://doi.org/10.1038/sj.gt.3302680

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