Pediatric Cardiology

, Volume 30, Issue 5, pp 699–709 | Cite as

Stem Cells from In- or Outside of the Heart: Isolation, Characterization, and Potential for Myocardial Tissue Regeneration

  • Willy A. Noort
  • Joost P. G. Sluijter
  • Marie-Jose Goumans
  • Steven A. J. Chamuleau
  • Pieter A. Doevendans
Riley Symposium

Abstract

Heart failure emerges with a net loss of viable cardiomyocytes, and there is no current therapy to reverse this process to improve long-term cardiac function. Due to a change in viewpoint, that the human heart cannot be considered a terminally differentiated postmitotic organ, incapable of myocardial regeneration, a belief in a new approach for therapy evolved: regenerating the heart. Finding stem cells in the heart capable of replenishing lost cardiomyocytes became a holy grail for research. Heart stem cells were isolated and characterized, originally derived from in- or outside of the heart. Since the endogenous repair potential of the heart following injury is not sufficient, cellular therapy has been performed after myocardial infarction in clinical settings. Clinical therapies performed with autologous skeletal myoblasts, cardiomyocytes, and bone marrow, as well as the animal studies, showed improvements in cardiac function, although the clinical effects are still limited. These findings have stimulated optimism that progression of heart failure might be prevented or even reversed with cell-based therapy. For future research, it will be a challenge to isolate the most potent therapeutic cell with an intrinsic capacity to stimulate regeneration in the heart, by direct participation or by producing paracrine factors.

Keywords

Stem cells Cellular therapy Regeneration of the heart 

Notes

Acknowledgments

Financial support was provided by a VIDI grant (016.056.319 from the Netherlands Organisation for Scientific Research (NWO), the BSIK programme (Dutch Programme for Tissue Engineering; UGT.6746), and the Netherlands Heart Foundation (2005T102).

References

  1. 1.
    Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al Mallah M, Dawn B (2007) Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 167:989–997PubMedCrossRefGoogle Scholar
  2. 2.
    Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822PubMedCrossRefGoogle Scholar
  3. 3.
    Al khaldi A, Robbins RC (2006) New directions in cardiac transplantation. Annu Rev Med 57:455–471PubMedCrossRefGoogle Scholar
  4. 4.
    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 102:11474–11479PubMedCrossRefGoogle Scholar
  5. 5.
    Anversa P, Kajstura J (1998) Ventricular myocytes are not terminally differentiated in the adult mammalian heart. Circ Res 83:1–14PubMedGoogle Scholar
  6. 6.
    Anversa P, Kajstura J, Leri A, Bolli R (2006) Life and death of cardiac stem cells:A paradigm shift in cardiac biology. Circulation 113:1451–1463PubMedCrossRefGoogle Scholar
  7. 7.
    Asahara T, Masuda H, Takahashi T, Kalka , Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228PubMedGoogle Scholar
  8. 8.
    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 106:3009–3017PubMedCrossRefGoogle Scholar
  9. 9.
    Au P, Daheron LM, Duda DG, Cohen KS, Tyrrell JA, Lanning RM, Fukumura D, Scadden DT, Jain RK (2008) Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood 111:1302–1305PubMedCrossRefGoogle Scholar
  10. 10.
    Au P, Tam J, Fukumura D, Jain RK (2007) Small blood vessel engineering. Methods Mol Med 140:183–195PubMedCrossRefGoogle Scholar
  11. 11.
    Barile L, Messina E, Giacomello A, Marban E (2007) Endogenous cardiac stem cells. Prog Cardiovasc Dis 50:31–38PubMedCrossRefGoogle Scholar
  12. 12.
    Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, Lecapitaine N, Cascapera S, Beltrami AP, D’Alessandro DA, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P (2007) Human cardiac stem cells. Proc Natl Acad Sci USA 104:14068–14073PubMedCrossRefGoogle Scholar
  13. 13.
    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 114:763–776PubMedCrossRefGoogle Scholar
  14. 14.
    Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 344:1750–1757PubMedCrossRefGoogle Scholar
  15. 15.
    Ben Shoshan J, George J (2007) Endothelial progenitor cells as therapeutic vectors in cardiovascular disorders:from experimental models to human trials. Pharmacol Ther 115:25–36PubMedCrossRefGoogle Scholar
  16. 16.
    Bergmann O, Bhardwaj R, Bernard S, Zdunek S, Walsh S, Zupicich J, ALkass K, Buchholz BA, Druid H, Jovinge S, Frisén J (2008) Turnover of human cardiomyocytes. Circulation 118:S500 abstractGoogle Scholar
  17. 17.
    Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X, Stallcup WB, Denton CP, McCulloch A, Chen J, Evans SM (2008) A myocardial lineage derives from Tbx18 epicardial cells. Nature 454:104–108PubMedCrossRefGoogle Scholar
  18. 18.
    Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084PubMedCrossRefGoogle Scholar
  19. 19.
    Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395PubMedCrossRefGoogle Scholar
  20. 20.
    Da Silva Meirelles L, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213PubMedCrossRefGoogle Scholar
  21. 21.
    Dimmeler SA, Zeiher M, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115:572–583PubMedGoogle Scholar
  22. 22.
    Dowell JD, Rubart M, Pasumarthi KB, Soonpaa MH, Field LJ (2003) Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res 58:336–350PubMedCrossRefGoogle Scholar
  23. 23.
    Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689PubMedCrossRefGoogle Scholar
  24. 24.
    Gianni AM, Siena S, Bregni M, Tarella C, Stern AC, Pileri A, Bonadonna G (1989) Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation. Lancet 2:580–585PubMedCrossRefGoogle Scholar
  25. 25.
    Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S (2001) Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 88:167–174PubMedGoogle Scholar
  26. 26.
    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 183:1797–1806PubMedCrossRefGoogle Scholar
  27. 27.
    Goumans MJ, de Boer TP, Smits AM, van Laake LW, van Vliet P, Metz CHG, Korfage TH, Kats TP, Hochstenbach R, Pasterkamp G, Verhaar MC, van der Heyden MAG, de Kleijn D, Mummery CL, van Veen TAB, Sluijter JPG, Doevendans PA (2008) TGF-ß1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res 1:138–149CrossRefGoogle Scholar
  28. 28.
    Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H, Ohtsuka M, Matsuura K, Sano M, Nishi J, Iwanaga K, Akazawa H, Kunieda T, Zhu W, Hasegawa H, Kunisada K, Nagai T, Nakaya H, Yamauchi-Takihara K, Komuro I (2005) G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med 11:305–311PubMedCrossRefGoogle Scholar
  29. 29.
    Harraz M, Jiao C, Hanlon HD, Hartley RS, Schatteman GC (2001) CD34- blood-derived human endothelial cell progenitors. Stem Cells 19:304–312PubMedCrossRefGoogle Scholar
  30. 30.
    Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA (2002) The post-natal heart contains a myocardial stem cell population. FEBS Lett 530:239–243PubMedCrossRefGoogle Scholar
  31. 31.
    Hirschi KK, Ingram DA, Yoder MC (2008) Assessing identity phenotype and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 28:1584–1595PubMedCrossRefGoogle Scholar
  32. 32.
    Hoogduijn MJ, Crop MJ, Peeters AM, Van Osch GJ, Balk AH, Ijzermans JN, Weimar W, Baan CC (2007) Human heart spleen and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev 16:597–604PubMedCrossRefGoogle Scholar
  33. 33.
    Hur J, Yoon CH, Kim HS, Choi JH, Kang HJ, Hwang KK, Oh BH, Lee MM, Park YB (2004) Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24:288–293PubMedCrossRefGoogle Scholar
  34. 34.
    Kattman SJ, Huber TL, Keller GM (2006) Multipotent flk–1+ cardiovascular progenitor cells give rise to the cardiomyocyte endothelial and vascular smooth muscle lineages. Dev Cell 11:723–732PubMedCrossRefGoogle Scholar
  35. 35.
    Keating A (2006) Mesenchymal stromal cells. Curr Opin Hematol 13:419–425PubMedCrossRefGoogle Scholar
  36. 36.
    Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856PubMedCrossRefGoogle Scholar
  37. 37.
    Laugwitz KL, Moretti A, Caron L, Nakano A, Chien KR (2008) Islet1 cardiovascular progenitors: a single source for heart lineages? Development 135:193–205PubMedCrossRefGoogle Scholar
  38. 38.
    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, Ringdén O, Developmental Committee of the European Group for Blood, Marrow Transplantation (2008) Mesenchymal stem cells for treatment of steroid-resistant severe acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586PubMedCrossRefGoogle Scholar
  39. 39.
    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 100:7808–7811PubMedCrossRefGoogle Scholar
  40. 40.
    Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA (1996) Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation 94:II332–II336Google Scholar
  41. 41.
    Li TS, Suzuki R, Ueda K, Murata T, Hamano K (2007) Analysis of the origin and population dynamics of cardiac progenitor cells in a donor heart model. Stem Cells 25:911–917PubMedCrossRefGoogle Scholar
  42. 42.
    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 102:8966–8971PubMedCrossRefGoogle Scholar
  43. 43.
    Luttun A, Carmeliet P (2003) De novo vasculogenesis in the heart. Cardiovasc Res 58:378–389PubMedCrossRefGoogle Scholar
  44. 44.
    Maekawa Y, Anzai T, Yoshikawa T, Sugano Y, Mahara K, Kohno T, Takahashi T, Ogawa S (2004) Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 44:1510–1520PubMedCrossRefGoogle Scholar
  45. 45.
    Martin-Puig S, Wang Z, Chien KR (2008) Lives of a heart cell: tracing the origins of cardiac progenitors. Cell Stem Cell 2:320–331PubMedCrossRefGoogle Scholar
  46. 46.
    Matsubara H (2004) Risk to the coronary arteries of intracoronary stem cell infusion and G-CSF cytokine therapy. Lancet 363:746–747PubMedCrossRefGoogle Scholar
  47. 47.
    Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384–11391PubMedCrossRefGoogle Scholar
  48. 48.
    Meissner K, Heydrich B, Jedlitschky G, Meyer Zu Schwabedissen H, Schwabedissen H, Mosyagin I, Dazert P, Eckel L, Vogelgesang S, Warzok RW, Bohm M, Lehmann C, Wendt M, Cascorbi I, Kroemer HK (2006) The ATP-binding cassette transporter ABCG2 (BCRP) a marker for side population stem cells is expressed in human heart. J Histochem Cytochem 54:215–221PubMedCrossRefGoogle Scholar
  49. 49.
    Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, Vilquin JT, Marolleau JP, Seymour B, Larghero J, Lake S, Chatellier G, Solomon S, Desnos M, Hagege AA (2008) The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117:1189–1200PubMedCrossRefGoogle Scholar
  50. 50.
    Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921PubMedCrossRefGoogle Scholar
  51. 51.
    Meckert PC, Rivello HG, Vigliano C, González P, Favaloro R, Laguens R (2005) Endomitosis and polyploidization of myocardial cells in the periphery of human acute myocardial infarction. Cardiovasc Res 67:116–123PubMedCrossRefGoogle Scholar
  52. 52.
    Moon MH, Kim SY, Kim YJ, Kim SJ, Lee JB, Bae YC, Sung SM, Jung JS (2006) Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol Biochem 17:279–290PubMedCrossRefGoogle Scholar
  53. 53.
    Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac smooth muscle and endothelial cell diversification. Cell 127:1151–1165PubMedCrossRefGoogle Scholar
  54. 54.
    Mudd JO, Kass DA (2008) Tackling heart failure in the twenty-first century. Nature 451:919–928PubMedCrossRefGoogle Scholar
  55. 55.
    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 428:664–668PubMedCrossRefGoogle Scholar
  56. 56.
    Nakanishi C, Yamagishi M, Yamahara K, Hagino I, Mori H, Sawa Y, Yagihara T, Kitamura S, Nagaya N (2008) Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells. Biochem Biophys Res Commun 374:11–16PubMedCrossRefGoogle Scholar
  57. 57.
    Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA (1996) Apoptosis in myocytes in end-stage heart failure. N Engl J Med 335:1182–1189PubMedCrossRefGoogle Scholar
  58. 58.
    Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506PubMedCrossRefGoogle Scholar
  59. 59.
    Noort WA, Kruisselbrink AB, in’t Anker PS, Kruger M, van Bezooijen RL, de Paus RA, Heemskerk MH, Lowik CW, Falkenburg JH, Willemze R, Fibbe WE (2002) Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol 30:870–878PubMedCrossRefGoogle Scholar
  60. 60.
    Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells from adult myocardium: homing differentiation and fusion after infarction. Proc Natl Acad Sci USA 100:12313–12318PubMedCrossRefGoogle Scholar
  61. 61.
    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 410:701–705PubMedCrossRefGoogle Scholar
  62. 62.
    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 98:10344–10349PubMedCrossRefGoogle Scholar
  63. 63.
    Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S (2000) Expression of VEGFR–2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95:952–958PubMedGoogle Scholar
  64. 64.
    Pfister O, Mouquet F, Jain M, Summer R, Helmes M, Fine A, Colucci WS, Liao R (2005) CD31− but not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res 97:52–61PubMedCrossRefGoogle Scholar
  65. 65.
    Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20PubMedCrossRefGoogle Scholar
  66. 66.
    Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002) Chimerism of the transplanted heart. N Engl J Med 346:5–15PubMedCrossRefGoogle Scholar
  67. 67.
    Rafii S, Lyden D (2003) Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 9:702–712PubMedCrossRefGoogle Scholar
  68. 68.
    Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y (2008) Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–e146PubMedCrossRefGoogle Scholar
  69. 69.
    Rota M, Padin-Iruegas ME, Misao Y, De Angelis A, Maestroni S, Ferreira-Martins J, Fiumana E, Rastaldo R, Arcarese ML, Mitchell TS, Boni A, Bolli R, Urbanek K, Hosoda T, Anversa P, Leri A, Kajstura J (2008) Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circ Res 103:107–116PubMedCrossRefGoogle Scholar
  70. 70.
    Rubart M, Field LJ (2006) Cardiac regeneration: repopulating the heart. Annu Rev Physiol 68:29–49PubMedCrossRefGoogle Scholar
  71. 71.
    Rubart M, Pasumarthi KB, Nakajima H, Soonpaa MH, Nakajima HO, Field LJ (2003) Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ Res 92:1217–1224PubMedCrossRefGoogle Scholar
  72. 72.
    Schafer R, Northoff H (2008) Cardioprotection and cardiac regeneration by mesenchymal stem cells. Panminerva Med 50:31–39PubMedGoogle Scholar
  73. 73.
    Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451:937–942PubMedCrossRefGoogle Scholar
  74. 74.
    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 73:1919–1925PubMedCrossRefGoogle Scholar
  75. 75.
    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 103:2776–2779PubMedCrossRefGoogle Scholar
  76. 76.
    Smits AM, van Laake LW, den Ouden K, Schreurs C, van Echteld CJ, Mummery CL, Doevendans PA, Goumans MJ (2008) Human cardiomyocyte progenitor cells regenerate infarcted myocardium and preserve long-term cardiac function in mice. Circulation 118:S499 (abstract)Google Scholar
  77. 77.
    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 5:434–438PubMedCrossRefGoogle Scholar
  78. 78.
    Takakura N, Watanabe T, Suenobu S, Yamada Y, Noda T, Ito Y, Satake M, Suda T (2000) A role for hematopoietic stem cells in promoting angiogenesis. Cell 102:199–209PubMedCrossRefGoogle Scholar
  79. 79.
    Timmers L, Lim SK, Arslan F, Armstrong JS, Hoefer IE, Doevendans PA, Piek JJ, El Oakley M, Choo A, Lee CN, Pasterkamp G, de Kleijn DPV (2008) Protection form myocardial reperfusion injury by human mesenchymal stem cell conditioned medium. Stem Cell Res 1:129–137CrossRefGoogle Scholar
  80. 80.
    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 105:93–98PubMedCrossRefGoogle Scholar
  81. 81.
    Torella D, Ellison GM, Karakikes I, Nadal-Ginard B (2007) Growth-factor-mediated cardiac stem cell activation in myocardial regeneration. Nat Clin Pract Cardiovasc Med 4:S46–S51PubMedCrossRefGoogle Scholar
  82. 82.
    Torella D, Ellison GM, Mendez-Ferrer S, Ibanez B, Nadal-Ginard B (2006) Resident human cardiac stem cells:role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med 3:S8–S13PubMedCrossRefGoogle Scholar
  83. 83.
    Traggiai E, Volpi S, Schena F, Gattorno M, Ferlito F, Moretta L, Martini A (2008) Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients. Stem Cells 26:562–569PubMedCrossRefGoogle Scholar
  84. 84.
    Urbanek K, Cesselli D, Rota M, Nascimbene A, De Angelis A, Hosoda T, Bearzi C, Boni A, Bolli R, Kajstura J, Anversa P, Leri A (2006) Stem cell niches in the adult mouse heart. Proc Natl Acad Sci USA 103:9226–9231PubMedCrossRefGoogle Scholar
  85. 85.
    Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA 102:8692–8697PubMedCrossRefGoogle Scholar
  86. 86.
    van Beem RT, Noort WA, Voermans C, Kleijer M, ten Brinke A, van Ham SM, van der Schoot CE, Zwaginga JJ (2008) The presence of activated CD4(+) T cells is essential for the formation of colony-forming unit-endothelial cells by CD14(+) cells. J Immunol 180:5141–5148PubMedGoogle Scholar
  87. 87.
    van Vliet P, Roccio M, Smits AM, van Oorschot AA, Metz CH, van Veen TA, Sluijter JP, Doevendans PA, Goumans MJ (2008) Progenitor cells isolated from the human heart: a potential cell source for regenerative therapy. Neth Heart J 16:163–169PubMedGoogle Scholar
  88. 88.
    Wang X, Hu Q, Nakamura Y, Lee J, Zhang G, From AH, Zhang J (2006) The role of the sca-1+/CD31-cardiac progenitor cell population in postinfarction LV remodeling. Stem Cells 24:1779–1788PubMedCrossRefGoogle Scholar
  89. 89.
    Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH (2006) Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell 127:1137–1150PubMedCrossRefGoogle Scholar
  90. 90.
    Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ, Kennedy M, Henckaerts E, Bonham K, Abbott GW, Linden RM, Field LJ, Keller GM (2008) Human cardiovascular progenitor cells develop from a KDR + embryonic-stem-cell-derived population. Nature 453:524–528PubMedCrossRefGoogle Scholar
  91. 91.
    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 115:326–338PubMedGoogle Scholar
  92. 92.
    Young PP, Vaughan DE, Hatzopoulos AK (2007) Biologic properties of endothelial progenitor cells and their potential for cell therapy. Prog Cardiovasc Dis 49:421–429PubMedCrossRefGoogle Scholar
  93. 93.
    Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE (2001) Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 33:907–921PubMedCrossRefGoogle Scholar
  94. 94.
    Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454:109–113PubMedCrossRefGoogle Scholar
  95. 95.
    Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7:1028–1034PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Willy A. Noort
    • 1
    • 2
  • Joost P. G. Sluijter
    • 1
    • 2
  • Marie-Jose Goumans
    • 3
  • Steven A. J. Chamuleau
    • 1
  • Pieter A. Doevendans
    • 1
    • 2
  1. 1.Division of Heart & Lungs, Department of Cardiology, Laboratory of Experimental CardiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Interuniversity Cardiology Institute of the NetherlandsUtrechtThe Netherlands
  3. 3.Department of Molecular Cell BiologyLeiden University Medical CenterLeidenThe Netherlands

Personalised recommendations