Basic Research in Cardiology

, Volume 100, Issue 6, pp 504–517 | Cite as

Cell–based cardiovascular repair

The Hurdles and the Opportunities
FOCUSED ISSUE: Cardiac Repair by Stem Cells


Cardiovascular cell therapy offers the first real potential to treat the underlying injuries associated with cardiac and vascular disease. By delivering appropriate exogenous cells to an injury site, the potential exists to mitigate injury or even to begin to reverse damage. Based on their inordinate pre–clinical promise as myogenic or angiogenic precursors, skeletal myoblasts and bone marrow or blood–derived mesenchymal and hematopoietic progenitor cells have all rapidly moved from bench to early clinical studies. From these parallel paths we are learning a number of useful lessons and have begun to visualize the hurdles to be overcome as we move these therapies forward.

It is now obvious that cell–based cardiac and vascular repair are feasible—both early and later in the disease process. In fact, cell therapy may offer an unparalleled opportunity for improvement to millions of individuals living with cardiovascular disease. However, many questions about the technology remain. The mechanisms associated with cardiovascular repair remain unclear. Whether a best cell type, delivery method, or route of administration exists is unknown. And, whether cellbased disease prevention is feasible is still unanswerable.

Now is the time to delve deeply into the questions of cell–based myocardial and vascular repair—even as we cautiously proceed clinically. Only by understanding these issues will we be able to decrease unanticipated clinical effects and to fulfill the potential promise of the most exciting opportunity yet to treat CVD. As we do so, we must prevent uncontrolled, poorly planned studies and until we understand cell therapy's potential, we must limit "too good to be true" promises. Only by addressing unanswered questions, carefully limiting our promises, and rigorously performing pre–clinical and clinical studies can we provide the surest opportunity for safely moving the field forward.

Key words

cell therapy heart failure myoblast bone marrow cardiac stem cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Miller LW, Missov ED (2001) Epidemiology of heart failure. Cardiol Clin 19:547–555CrossRefPubMedGoogle Scholar
  2. 2.
    World Health Report (2003) At: www. who. int/whr/en/Google Scholar
  3. 3.
    Cohn JN, Francis GS (1995) Cardiac failure: a revised paradigm. J Card Fail 1:261–266CrossRefPubMedGoogle Scholar
  4. 4.
    Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML (2002) Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346:877–883CrossRefPubMedGoogle Scholar
  5. 5.
    Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M (1996) Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med. 335:1933–1940CrossRefPubMedGoogle Scholar
  6. 6.
    Hertz MI, Taylor DO, Trulock EP, Boucek MM, Mohacsi PJ, Edwards LB, Keck BM (2002) The registry of the international society for heart and lung transplantation: nineteenth official report–2002. J Heart Lung Transplant 21:950–970CrossRefPubMedGoogle Scholar
  7. 7.
    Bank AJ, Mir SH, Nguyen DQ, Bolman RM, 3rd, Shumway SJ, Miller LW, Kaiser DR, Ormaza SM, Park SJ (2000) Effects of left ventricular assist devices on outcomes in patients undergoing heart transplantation. Ann Thorac Surg 69:1369–1374; discussion 1375CrossRefPubMedGoogle Scholar
  8. 8.
    Lietz K, Miller LW (2005) Will left–ventricular assist device therapy replace heart transplantation in the foreseeable future? Curr Opin Cardiol 20:132–137CrossRefPubMedGoogle Scholar
  9. 9.
    Miller LW (2003) Patient selection for the use of ventricular assist devices as a bridge to transplantation. Ann Thorac Surg 75:S66–S71CrossRefPubMedGoogle Scholar
  10. 10.
    Stevenson LW, Miller LW, Desvigne–Nickens P, Ascheim DD, Parides MK, Renlund DG, Oren RM, Krueger SK, Costanzo MR, Wann LS, Levitan RG, Mancini D (2004) Left ventricular assist device as destination for patients undergoing intravenous inotropic therapy: a subset analysis from REMATCH (Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure). Circulation 110:975–981CrossRefPubMedGoogle Scholar
  11. 11.
    Mancini DM, Beniaminovitz A, Levin H, Catanese K, Flannery M, DiTullio M, Savin S, Cordisco ME, Rose E, Oz M (1998) Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure. Circulation. 98:2383–2389PubMedGoogle Scholar
  12. 12.
    Stuck WG, O’Donoghue DH et al. (1949) Fractures. Arch Surg 59:1139–1190PubMedGoogle Scholar
  13. 13.
    Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, Glower DD, Kraus WE (1998) Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nature Medicine 4:929– 933CrossRefPubMedGoogle Scholar
  14. 14.
    Bonaros N, Yang S, Ott H, Kocher A (2004) Cell therapy for ischemic heart disease. Panminerva Med 46:13–23PubMedGoogle Scholar
  15. 15.
    Pouzet B, Ghostine S, Vilquin JT, Garcin I, Scorsin M, Hagege AA, Duboc D, Schwartz K, Menasche P (2001) Is skeletal myoblast transplantation clinically relevant in the era of angiotensin–converting enzyme inhibitors? Circulation 104:I223–I228PubMedGoogle Scholar
  16. 16.
    Menasche P, Hagege A, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin J, Marroleau J (2001) Myoblast transplantation for heart failure. The Lancet 357:279–280CrossRefGoogle Scholar
  17. 17.
    Wollert KC, Drexler H (2005) Clinical applications of stem cells for the heart. Circ Res 96:151–163CrossRefPubMedGoogle Scholar
  18. 18.
    Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bonemarrow stem–cell transplantation for myocardial regeneration. Lancet 361:45–46CrossRefPubMedGoogle Scholar
  19. 19.
    Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE–AMI). Circulation 106:3009–3017CrossRefPubMedGoogle Scholar
  20. 20.
    Rauscher FM, Goldschmidt–Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA (2003) Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108:457–463CrossRefPubMedGoogle Scholar
  21. 21.
    Itescu S, Kocher AA, Schuster MD (2003) Myocardial neovascularization by adult bone marrow–derived angioblasts: strategies for improvement of cardiomyocyte function. Heart Fail Rev 8:253–258CrossRefPubMedGoogle Scholar
  22. 22.
    Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz–Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49CrossRefPubMedGoogle Scholar
  23. 23.
    Hutcheson KA, Atkins BZ, Hueman MT, Hopkins MB, Glower DD, Taylor DA (2000) Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts. Cell Transplant 9:359–368PubMedGoogle Scholar
  24. 24.
    Horackova M, Arora R, Chen R, Armour JA, Cattini PA, Livingston R, Byczko Z (2004) Cell transplantation for treatment of acute myocardial infarction: unique capacity for repair by skeletal muscle satellite cells. Am J Physiol Heart Circ Physiol 287:H1599–H1608CrossRefPubMedGoogle Scholar
  25. 25.
    Ott HC, Bonaros N, Marksteiner R, Wolf D, Margreiter E, Schachner T, Laufer G, Hering S (2004) Combined transplantation of skeletal myoblasts and bone marrow stem cells for myocardial repair in rats. Eur J Cardiothorac Surg 25:627–634CrossRefPubMedGoogle Scholar
  26. 26.
    Thompson RB, Emani SM, Davis BH, van den Bos EJ, Morimoto Y, Craig D, Glower D, Taylor DA (2003) Comparison of intracardiac cell transplantation: autologous skeletal myoblasts versus bone marrow cells. Circulation 108 (Suppl 1):II264–II271CrossRefPubMedGoogle Scholar
  27. 27.
    Agbulut O, Vandervelde S, Al Attar N, Larghero J, Ghostine S, Leobon B, Robidel E, Borsani P, Le Lorc'h M, Bissery A, Chomienne C, Bruneval P, Marolleau JP, Vilquin JT, Hagege A, Samuel JL, Menasche P (2004) Comparison of human skeletal myoblasts and bone marrow– derived CD133+ progenitors for the repair of infarcted myocardium. J Am Coll Cardiol 44:458–463CrossRefPubMedGoogle Scholar
  28. 28.
    Field L (1998) Future therapy for cardiovascular disease. In: NHLBI Workshop Cell Transplantation: Future Therapy for Cardiovascular Disease? Columbia, MDGoogle Scholar
  29. 29.
    Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin JT, Marolleau JP (2001) Myoblast transplantation for heart failure. Lancet 357:279–280CrossRefGoogle Scholar
  30. 30.
    Taylor DA, Silvestry SC, Bishop SP, Annex BH, Lilly RE, Glower DD, Kraus WE (1997) Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair. Proceedings of the Association of American Physicians 109:245–253PubMedGoogle Scholar
  31. 31.
    Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belem L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107:2294–2302CrossRefPubMedGoogle Scholar
  32. 32.
    Siminiak T, Fiszer D, Jerzykowska O, Grygielska B, Rozwadowska N, Kalmucki P, Kurpisz M (2005) Percutaneous transcoronary– venous transplantation of autologous skeletal myoblasts in the treatment of post–infarction myocardial contractility impairment: the POZNAN trial. Eur Heart J 26:1188–1195CrossRefPubMedGoogle Scholar
  33. 33.
    Dib N, McCarthy P, Campbell A, Yeager M, Pagani FD, Wright S, MacLellan WR, Fonarow G, Eisen HJ, Michler RE, Binkley P, Buchele D, Korn R, Ghazoul M, Dinsmore J, Opie SR, Diethrich E (2005) Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplant 14:11–19PubMedGoogle Scholar
  34. 34.
    Smits PC, van Geuns RJ, Poldermans D, Bountioukos M, Onderwater EE, Lee CH, Maat AP, Serruys PW (2003) Catheterbased 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 42:2063–2069CrossRefPubMedGoogle Scholar
  35. 35.
    Thompson RB, Parsa CJ, van den Bos EJ, Davis BH, Toloza EM, Klem I, Glower DD, Taylor DA (2004) Video–assisted thoracoscopic transplantation of myoblasts into the heart. Ann Thorac Surg 78:303–307CrossRefPubMedGoogle Scholar
  36. 36.
    Thompson CA, Nasseri BA, Makower J, Houser S, McGarry M, Lamson T, Pomerantseva I, Chang JY, Gold HK, Vacanti JP, Oesterle SN (2003) Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation. J Am Coll Cardiol 41:1964–1971CrossRefPubMedGoogle Scholar
  37. 37.
    Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361:47–49CrossRefPubMedGoogle Scholar
  38. 38.
    Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, Baffour R, Waksman R, Weissman NJ, Cerqueira M, Leon MB, Epstein SE (2003) Catheterbased autologous bone marrow myocardial injection in no–option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 41:1721–1724CrossRefPubMedGoogle Scholar
  39. 39.
    Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV, Mesquita CT, Belem L, Vaughn WK, Rangel FO, Assad JA, Carvalho AC, Branco RV, Rossi MI, Dohmann HJ, Willerson JT (2004) Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 110:II213–II218CrossRefPubMedGoogle Scholar
  40. 40.
    Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, Wernet P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918CrossRefPubMedGoogle Scholar
  41. 41.
    Saito T, Kuang JQ, Bittira B, Al–Khaldi A, Chiu RC (2002) Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 74:19–24; discussion 24CrossRefPubMedGoogle Scholar
  42. 42.
    Vulliet PR, Greeley M, Halloran SM, Mac– Donald KA, Kittleson MD (2004) Intracoronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363:783–784CrossRefPubMedGoogle Scholar
  43. 43.
    Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z (2003) Transdifferentiation of human peripheral blood CD34+–enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 108:2070–2073CrossRefPubMedGoogle Scholar
  44. 44.
    Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, Eckey T, Henze E, Zeiher AM, Dimmeler S (2003) Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 107:2134–2139CrossRefPubMedGoogle Scholar
  45. 45.
    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 108:863–868CrossRefPubMedGoogle Scholar
  46. 46.
    Chin BB, Nakamoto Y, Bulte JW, Pittenger MF, Wahl R, Kraitchman DL (2003) 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun 24:1149–1154CrossRefPubMedGoogle Scholar
  47. 47.
    Alessandrino P, Bernasconi P, Caldera D, Colombo A, Bonfichi M, Malcovati L, Klersy C, Martinelli G, Maiocchi M, Pagnucco G, Varettoni M, Perotti C, Bernasconi C (1999) Adverse events occurring during bone marrow or peripheral blood progenitor cell infusion: analysis of 126 cases. Bone Marrow Transplant 23:533–537CrossRefPubMedGoogle Scholar
  48. 48.
    Menasche P, Hagege AA, Vilquin JT, Desnos M, Abergel E, Pouzet B, Bel A, Sarateanu S, Scorsin M, Schwartz K, Bruneval P, Benbunan M, Marolleau JP, Duboc D (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41:1078–1083CrossRefPubMedGoogle Scholar
  49. 49.
    Chachques JC, Herreros J, Trainini J, Juffe A, Rendal E, Prosper F, Genovese J (2004) Autologous human serum for cell culture avoids the implantation of cardioverterdefibrillators in cellular cardiomyoplasty. Int J Cardiol 95 (Suppl 1):S29–S33CrossRefPubMedGoogle Scholar
  50. 50.
    Koyanagi M, Brandes RP, Haendeler J, Zeiher AM, Dimmeler S (2005) Cell–tocell connection of endothelial progenitor cells with cardiac myocytes by nanotubes: a novel mechanism for cell fate changes? Circ Res 96:1039–1041CrossRefPubMedGoogle Scholar
  51. 51.
    Driesen RB, Dispersyn GD, Verheyen FK, van den Eijnde SM, Hofstra L, Thone F, Dijkstra P, Debie W, Borgers M, Ramaekers FC (2005) Partial cell fusion: A newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts. Cardiovasc Res 68:37–46CrossRefPubMedGoogle Scholar
  52. 52.
    Yoon J, Shim WJ, Ro YM, Lim DS (2005) Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell–to–cell contact with neonatal cardiomyocyte but not adult cardiomyocytes. Ann Hematol (in press)Google Scholar
  53. 53.
    Matsuura K, Wada H, Nagai T, Iijima Y, Minamino T, Sano M, Akazawa H, Molkentin JD, Kasanuki H, Komuro I (2004) Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle. J Cell Biol 167:351–363CrossRefPubMedGoogle Scholar
  54. 54.
    Schmidt–Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, Dimmeler S, Zeiher AM (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111:2981–2987CrossRefPubMedGoogle Scholar
  55. 55.
    Kravchenko J, Goldschmidt–Clermont PJ, Powell T, Stallard E, Akushevich I, Cuffe MS, Manton KG (2005) Endothelial progenitor cell therapy for atherosclerosis: the philosopher’s stone for an aging population? Sci Aging Knowledge Environ 2005: pe18CrossRefPubMedGoogle Scholar
  56. 56.
    Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S (2001) Neovascularization of ischemic myocardium by human bone–marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7:430–436CrossRefPubMedGoogle Scholar
  57. 57.
    Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal–Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705CrossRefPubMedGoogle Scholar
  58. 58.
    Stamm C, Kleine HD, Westphal B, Petzsch M, Kittner C, Nienaber CA, Freund M, Steinhoff G (2004) CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg 52:152–158CrossRefPubMedGoogle Scholar
  59. 59.
    Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one–year results of the TOPCARE–AMI Trial. J Am Coll Cardiol 44:1690–1699CrossRefPubMedGoogle Scholar
  60. 60.
    Wollert KC, Meyer GP, Lotz J, Ringes– Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H (2004) Intracoronary autologous bone–marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148CrossRefPubMedGoogle Scholar
  61. 61.
    Janssens S (2005) Intracoronary Autologous Bone–Marrow Cell Transfer after Myocardial Infarction: A Double–Blind, Randomized, and Placebo–Controlled Clinical Trial. American College of Cardiology Scientific SessionsGoogle Scholar
  62. 62.
    Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, Avogaro A (2005) Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 45:1449–1457CrossRefPubMedGoogle Scholar
  63. 63.
    Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007CrossRefPubMedGoogle Scholar
  64. 64.
    Opie SR, Dib N (2004) Local endovascular delivery, gene therapy, and cell transplantation for peripheral arterial disease. J Endovasc Ther 11 (Suppl 2):II151–II162CrossRefPubMedGoogle Scholar
  65. 65.
    Iwase T, Nagaya N, Fujii T, Itoh T, Murakami S, Matsumoto T, Kangawa K, Kitamura S (2005) Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res 66:543–551CrossRefPubMedGoogle Scholar
  66. 66.
    Tateishi–Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T (2002) Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bonemarrow cells: a pilot study and a randomised controlled trial. Lancet 360:427–435CrossRefPubMedGoogle Scholar
  67. 67.
    Higashi Y, Kimura M, Hara K, Noma K, Jitsuiki D, Nakagawa K, Oshima T, Chayama K, Sueda T, Goto C, Matsubara H, Murohara T, Yoshizumi M (2004) Autologous bone–marrow mononuclear cell implantation improves endotheliumdependent vasodilation in patients with limb ischemia. Circulation 109:1215–1218CrossRefPubMedGoogle Scholar
  68. 68.
    Sakakibara Y, Nishimura K, Tambara K, Yamamoto M, Lu F, Tabata Y, Komeda M (2002) Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation. J Thorac Cardiovasc Surg 124:50–56CrossRefPubMedGoogle Scholar
  69. 69.
    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 9:1195–1201CrossRefPubMedGoogle Scholar
  70. 70.
    Ott HC, Berjukow S, Marksteiner R, Margreiter E, Bock G, Laufer G, Hering S (2004) On the fate of skeletal myoblasts in a cardiac environment: down–regulation of voltage–gated ion channels. J Physiol 558:793–805CrossRefPubMedGoogle Scholar
  71. 71.
    Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S (2003) Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci USA 100:7808–7811CrossRefPubMedGoogle Scholar
  72. 72.
    Vandervelde S, van Luyn MJ, Tio RA, Harmsen MC (2005) Signaling factors in stem cell–mediated repair of infarcted myocardium. J Mol Cell Cardiol (in press)Google Scholar
  73. 73.
    Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, Yacoub MH (2001) Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factorexpressing skeletal myoblasts. Circulation 104:I207–I212PubMedGoogle Scholar
  74. 74.
    Reinecke H, Minami E, Virag JI, Murry CE (2004) Gene transfer of connexin43 into skeletal muscle. Hum Gene Ther 15:627–636CrossRefPubMedGoogle Scholar
  75. 75.
    Guttinger M, Padrun V, Pralong WF, Boison D (2005) Seizure suppression and lack of adenosine A1 receptor desensitization after focal long–term delivery of adenosine by encapsulated myoblasts. Exp Neurol 193:53–64CrossRefPubMedGoogle Scholar
  76. 76.
    Koyanagi M, Haendeler J, Badorff C, Brandes RP, Hoffmann J, Pandur P, Zeiher AM, Kuhl M, Dimmeler S (2005) Non–canonical Wnt signaling enhances differentiation of human circulating progenitor cells to cardiomyogenic cells. J Biol Chem 280:16838–16842CrossRefPubMedGoogle Scholar
  77. 77.
    Kittleson MM, Minhas KM, Irizarry RA, Ye SQ, Edness G, Breton E, Conte JV, Tomaselli G, Garcia JG, Hare JM (2005) Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure. Physiol Genomics 21:299–307CrossRefPubMedGoogle Scholar
  78. 78.
    Herreros J, Prosper F, Perez A, Gavira JJ, Garcia–Velloso MJ, Barba J, Sanchez PL, Canizo C, Rabago G, Marti–Climent JM, Hernandez M, Lopez–Holgado N, Gonzalez–Santos JM, Martin–Luengo C, Alegria E (2003) Autologous intramyocardial injection of cultured skeletal muscle–derived stem cells in patients with non–acute myocardial infarction. Eur Heart J 24:2012–2020CrossRefPubMedGoogle Scholar
  79. 79.
    Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzezniczak J, Rozwadowska N, Kurpisz M (2004) Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow–up. Am Heart J 148:531–537CrossRefPubMedGoogle Scholar
  80. 80.
    Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K (2001) Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 65:845–847CrossRefPubMedGoogle Scholar
  81. 81.
    Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin H, Schachinger V, Dimmeler S, Zeiher AM (2003) 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 108:2212–2218CrossRefPubMedGoogle Scholar
  82. 82.
    Fernandez–Aviles F, San Roman JA, Garcia–Frade J, Fernandez ME, Penarrubia MJ, de la Fuente L, Gomez–Bueno M, Cantalapiedra A, Fernandez J, Gutierrez O, Sanchez PL, Hernandez C, Sanz R, Garcia–Sancho J, Sanchez A (2004) Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 95:742–748CrossRefPubMedGoogle Scholar
  83. 83.
    Kuethe F, Richartz BM, Sayer HG, Kasper C, Werner GS, Hoffken K, Figulla HR (2004) Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. Int J Cardiol 97:123–127CrossRefPubMedGoogle Scholar
  84. 84.
    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 94:92–95CrossRefPubMedGoogle Scholar
  85. 85.
    Vanderheyden M MS, Vandekerckhove B, De Bondt P, VanHAute I, Lootens N, DeBruyne B, Heyndrickx GR, Wijns W, Bartunek J (2004) Selected intracoronary CD133+ bone marrow cells promote cardiac regeneration after acute myocardial infarction. Circ 110:324–325CrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  1. 1.Center for Cardiovascular Repair University of MinnesotaUSA
  2. 2.Center for Cardiovascular RepairUniversity of MinnesotaMinneapolisUSA

Personalised recommendations