Basic Research in Cardiology

, Volume 100, Issue 6, pp 494–503 | Cite as

Adult bone marrow–derived cells: Regenerative potential, plasticity, and tissue commitment

FOCUSED ISSUE: Cardiac Repair by Stem Cells

Abstract

Reconstitution of infarcted myocardium with functional new cardiomyocytes and vessels, a goal that only a few years ago would have been regarded as extravagant, is now actively pursued in numerous laboratories and clinical centers. Several recent studies in animals as well as humans have shown that transplantation of adult bone marrow–derived cells (BMCs) can improve left ventricular function and halt adverse remodeling after myocardial infarction. Differentiation of adult BMCs into cells of cardiac and vascular lineages has been proposed as a mechanism underlying these benefits and, indeed, differentiation of adult BMCs into cells of non–hematopoietic lineages, including cells of brain, skeletal muscle, heart, liver, and other organs, has been documented repeatedly both in vitro and in vivo. These results are in contrast with conventional definitions and dogma, according to which adult tissue–specific stem cells exhibit only restricted differentiation potential. Thus, these recent studies have sparked intense debate over the ability of adult BMCs to differentiate into non–hematopoietic tissues, and the regeneration of myocardium by differentiation of adult BMCs remains highly controversial. Because of the enormous clinical implications of BMCmediated cardiac repair, numerous laboratories are currently addressing the feasibility of cardiac regeneration with BMCs and deciphering the mechanism underlying the beneficial effects. The purpose of this review is to critically examine the available evidence regarding the ability of adult BMCs to regenerate non–hematopoietic tissues and their utility in therapeutic cardiac regeneration.

Key words

myocardial regeneration stem cell bone marrow plasticity tissue–commitment 

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References

  1. 1.
    Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94:4080–4085CrossRefPubMedGoogle Scholar
  2. 2.
    Ferrari G, Cusella–De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F (1998) Muscle regeneration by bone marrow–derived myogenic progenitors. Science 279:1528–1530CrossRefPubMedGoogle Scholar
  3. 3.
    Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284:1168–1170CrossRefPubMedGoogle Scholar
  4. 4.
    Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, Sakai T, Jia ZQ (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100 (19 Suppl):II247–II256PubMedGoogle Scholar
  5. 5.
    Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779–1782CrossRefPubMedGoogle Scholar
  6. 6.
    Lagasse E, Connors H, Al–Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234CrossRefPubMedGoogle Scholar
  7. 7.
    Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS (2000) Derivation of hepatocytes from bone marrow cells in mice after radiationinduced myeloablation. Hepatology 31:235–240CrossRefPubMedGoogle Scholar
  8. 8.
    Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS (2000) Liver from bone marrow in humans. Hepatology 32:11–16CrossRefPubMedGoogle Scholar
  9. 9.
    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
  10. 10.
    Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, Pittenger MF, Martin BJ (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73:1919–1925; discussion 1926CrossRefPubMedGoogle Scholar
  11. 11.
    Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11–20CrossRefPubMedGoogle Scholar
  12. 12.
    Kucia M, Dawn B, Hunt G, Guo Y, Wysoczynski M, Majka M, Ratajczak J, Rezzoug F, Ildstad ST, Bolli R, Ratajczak MZ (2004) Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction. Circ Res 95:1191–1199CrossRefPubMedGoogle Scholar
  13. 13.
    Bailey AS, Jiang S, Afentoulis M, Baumann CI, Schroeder DA, Olson SB, Wong MH, Fleming WH (2004) Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood 103:13–19CrossRefPubMedGoogle Scholar
  14. 14.
    Almeida–Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED (2004) Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood 104:2582–2590CrossRefPubMedGoogle Scholar
  15. 15.
    Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, Hanley A, Scadova H, Qin G, Cha DH, Johnson KL, Aikawa R, Asahara T, Losordo DW (2005) Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 115:326–338CrossRefPubMedGoogle Scholar
  16. 16.
    Wagers AJ, Sherwood RI, Christensen JL, Weissman IL (2002) Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297:2256–2259CrossRefPubMedGoogle Scholar
  17. 17.
    Alvarez–Dolado M, Pardal R, Garcia– Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez–Buylla A (2003) Fusion of bone–marrow–derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–973CrossRefPubMedGoogle Scholar
  18. 18.
    Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al–Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M (2003) Cell fusion is the principal source of bone–marrow–derived hepatocytes. Nature 422:897–901CrossRefPubMedGoogle Scholar
  19. 19.
    Vassilopoulos G, Wang PR, Russell DW (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature 422:901–904CrossRefPubMedGoogle Scholar
  20. 20.
    Vassilopoulos G, Russell DW (2003) Cell fusion: an alternative to stem cell plasticity and its therapeutic implications. Curr Opin Genet Dev 13:480–485CrossRefPubMedGoogle Scholar
  21. 21.
    Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428:668–673CrossRefPubMedGoogle Scholar
  22. 22.
    Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428:664–668CrossRefPubMedGoogle Scholar
  23. 23.
    Chien KR (2004) Stem cells: lost in translation. Nature 428:607–608CrossRefPubMedGoogle Scholar
  24. 24.
    Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779CrossRefPubMedGoogle Scholar
  25. 25.
    Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401:390–394CrossRefPubMedGoogle Scholar
  26. 26.
    Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia– and cytokine–induced mobilization of bone marrow–derived endothelial progenitor cells for neovascularization. Nat Med 5:434–348CrossRefPubMedGoogle Scholar
  27. 27.
    Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103:634–637PubMedGoogle Scholar
  28. 28.
    Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T (2003) Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 107:461–468CrossRefPubMedGoogle Scholar
  29. 29.
    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
  30. 30.
    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
  31. 31.
    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
  32. 32.
    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
  33. 33.
    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
  34. 34.
    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
  35. 35.
    Fuchs E, Segre JA (2000) Stem cells: a new lease on life. Cell 100:143–155CrossRefPubMedGoogle Scholar
  36. 36.
    Poulsom R, Alison MR, Forbes SJ, Wright NA (2002) Adult stem cell plasticity. J Pathol 197:441–456CrossRefPubMedGoogle Scholar
  37. 37.
    Gunsilius E, Gastl G, Petzer AL (2001) Hematopoietic stem cells. Biomed Pharmacother 55:186–194CrossRefPubMedGoogle Scholar
  38. 38.
    Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20CrossRefPubMedGoogle Scholar
  39. 39.
    Asahara T, Kawamoto A (2004) Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol 287:C572–C579CrossRefPubMedGoogle Scholar
  40. 40.
    Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353CrossRefPubMedGoogle Scholar
  41. 41.
    Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183:1797–1806CrossRefPubMedGoogle Scholar
  42. 42.
    Pearce DJ, Ridler CM, Simpson C, Bonnet D (2004) Multiparameter analysis of murine bone marrow side population cells. Blood 103:2541–2546CrossRefPubMedGoogle Scholar
  43. 43.
    Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM (2002) Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 30:896–904CrossRefPubMedGoogle Scholar
  44. 44.
    Howell JC, Lee WH, Morrison P, Zhong J, Yoder MC, Srour EF (2003) Pluripotent stem cells identified in multiple murine tissues. Ann N Y Acad Sci 996:158–173PubMedGoogle Scholar
  45. 45.
    Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska–Wieczorek A, Ratajczak J (2004) Stem cell plasticity revisited: CXCR4–positive cells expressing mRNA for early muscle, liver and neural cells ‘hide out’ in the bone marrow. Leukemia 18:29–40CrossRefPubMedGoogle Scholar
  46. 46.
    Kucia M, Ratajczak J, Reca R, Janowska–Wieczorek A, Ratajczak MZ (2004) Tissue– specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF–1 gradient and are mobilized into peripheral blood during stress and tissue injury. Blood Cells Mol Dis 32:52–57CrossRefPubMedGoogle Scholar
  47. 47.
    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 105:93–98CrossRefPubMedGoogle Scholar
  48. 48.
    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 103:697–705PubMedGoogle Scholar
  49. 48a.
    Kawada H, Fujita J, Kinjo K, Matsuzaki Y, Tsuma M, Mlyatake H, Muguruma Y, Tsubol K, Itabashi Y, Ikeda Y, Ogawa S, Okano H, Hotta T, Ando K, Fukuda K (2004) Nonhematopoletic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood 104:3581–3587CrossRefPubMedGoogle Scholar
  50. 48b.
    Hattan N, Kawaguchi H, Ando K, Kuwabara E, Fujita J, Murata M, Suematsu M, Mori H, Fukuda K (2005) Purified cardiomyocytes from bone marrow mesenchymal stem cells produce stable intracardiac grafts in mice. Cardiovasc Res 65:334–344CrossRefPubMedGoogle Scholar
  51. 49.
    Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ (2004) Mobilization of CD34/CXCR4+, CD34/CD117+, c–met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation 110:3213–3220CrossRefPubMedGoogle Scholar
  52. 50.
    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
  53. 51.
    Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103:2776–2779PubMedGoogle Scholar
  54. 52.
    Badorff C, Brandes RP, Popp R, Rupp S, Urbich C, Aicher A, Fleming I, Busse R, Zeiher AM, Dimmeler S (2003) Transdifferentiation of blood–derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation 107:1024–1032CrossRefPubMedGoogle Scholar
  55. 53.
    Korbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, Champlin RE, Estrov Z (2002) Hepatocytes and epithelial cells of donor origin in recipients of peripheral–blood stem cells. N Engl J Med 346:738–746CrossRefPubMedGoogle Scholar
  56. 54.
    Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, Ikeda Y, Hibi T, Inazawa J, Watanabe M (2002) Damaged epithelia regenerated by bone marrow–derived cells in the human gastrointestinal tract. Nat Med. 2002 Sep; 8 (9):1011–1017 8:1011–1017CrossRefPubMedGoogle Scholar
  57. 55.
    Anversa P, Nadal–Ginard B (2002) Cardiac chimerism: methods matter. Circulation 106:e129–131CrossRefPubMedGoogle Scholar
  58. 56.
    Hernandez LD, Hoffman LR, Wolfsberg TG, White JM (1996) Virus–cell and cellcell fusion. Annu Rev Cell Dev Biol 12:627–661CrossRefPubMedGoogle Scholar
  59. 57.
    Duelli D, Lazebnik Y (2003) Cell fusion: a hidden enemy? Cancer Cell 3:445–448CrossRefPubMedGoogle Scholar
  60. 58.
    Kajstura J, Rota M, Whang B, Cascapera S, Hosoda T, Bearzi C, Nurzynska D, Kasahara H, Zias E, Bonafe M, Nadal– Ginard B, Torella D, Nascimbene A, Quaini F, Urbanek K, Leri A, Anversa P (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96:127–137CrossRefPubMedGoogle Scholar
  61. 59.
    Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal–Ginard B, Anversa P (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776CrossRefPubMedGoogle Scholar
  62. 60.
    Dawn B, Stein AB, Urbanek K, Rota M, Whang B, Rastaldo R, Torella D, Tang XL, Rezazadeh A, Kajstura J, Leri A, Hunt G, Varma J, Prabhu SD, Anversa P, Bolli R (2005) Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci USA 102:3766–3771CrossRefPubMedGoogle Scholar
  63. 61.
    Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal–Ginard B, Bodine DM, Leri A, Anversa P (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98:10344–10349CrossRefPubMedGoogle Scholar
  64. 62.
    Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bone–marrow stem–cell transplantation for myocardial regeneration. Lancet 361:45–46CrossRefPubMedGoogle Scholar
  65. 63.
    Tosh D, Slack JM (2002) How cells change their phenotype. Nat Rev Mol Cell Biol 3:187–194CrossRefPubMedGoogle Scholar
  66. 64.
    Martin–Rendon E, Watt SM (2003) Stem cell plasticity. Br J Hematol 122:877–891CrossRefGoogle Scholar
  67. 65.
    Ratajczak MZ, Kucia M, Majka M, Reca R, Ratajczak J (2004) Heterogeneous populations of bone marrow stem cells–are we spotting on the same cells from the different angles? Folia Histochem Cytobiol 42:139–146PubMedGoogle Scholar
  68. 66.
    Kucia M, Reca R, Jala VR, Dawn B, Ratajczak J, Ratajczak MZ (2005) Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells. Leukemia 19:1118–1127CrossRefPubMedGoogle Scholar
  69. 67.
    Kucia M, Ratajczak J, Ratajczak MZ (2005) Are bone marrow stem cells plastic or heterogenous–That is the question. Exp Hematol 33:613–623CrossRefPubMedGoogle Scholar
  70. 68.
    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
  71. 69.
    Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte–like cells. J Clin Invest 109:1291–1302CrossRefPubMedGoogle Scholar
  72. 70.
    Jiang Y, Henderson D, Blackstad M, Chen A, Miller RF, Verfaillie CM (2003) Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proc Natl Acad Sci USA 100 (Suppl 1):11854–11860CrossRefPubMedGoogle Scholar
  73. 71.
    Association AH (1996) Heart and stroke facts. Statistical Supplement: 1–23Google Scholar
  74. 72.
    Pfeffer MA, Pfeffer JM, Lamas GA (1993) Development and prevention of congestive heart failure following myocardial infarction. Circulation 87:IV120–IV125PubMedGoogle Scholar
  75. 73.
    Maekawa Y, Anzai T, Yoshikawa T, Sugano Y, Mahara K, Kohno T, Takahashi T, Ogawa S (2004) Effect of granulocytemacrophage colony–stimulating factor inducer on left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 44:1510–1520CrossRefPubMedGoogle Scholar
  76. 74.
    Valgimigli M, Rigolin GM, Cittanti C, Malagutti P, Curello S, Percoco G, Bugli AM, Porta MD, Bragotti LZ, Ansani L, Mauro E, Lanfranchi A, Giganti M, Feggi L, Castoldi G, Ferrari R (2005) Use of granulocyte–colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile. Eur Heart J 26:1838–1845CrossRefPubMedGoogle Scholar
  77. 75.
    Wang Y, Tagil K, Ripa RS, Nilsson JC, Carstensen S, Jorgensen E, Sondergaard L, Hesse B, Johnsen HE, Kastrup J (2005) Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease. Int J Cardiol 100:477–483CrossRefPubMedGoogle Scholar
  78. 76.
    Wollert KC, Drexler H (2005) Clinical applications of stem cells for the heart. Circ Res 96:151–163CrossRefPubMedGoogle Scholar
  79. 77.
    Bolli R, Jneid H, Dawn B (2005) Bone marrow cell–mediated cardiac regeneration: a veritable revolution. J Am Coll Cardiol (in press)Google Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  1. 1.Division of CardiologyInstitute of Molecular Cardiology, University of LouisvilleLouisvilleKY 40292

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