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Cardiac regeneration by resident stem and progenitor cells in the adult heart

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Abstract

Two main pieces of data have created a new field in cardiac research. First, the traditional view on the heart as a postmitotic organ has been challenged by the finding of small dividing cells in the heart expressing cardiac contractile proteins with stem cell properties and, second, cellular therapy of the diseased heart using a variety of different cells has shown encouraging effects on cardiac function. These findings immediately raise questions like "what is the identity and origin of the cardiac progenitor cells?","which molecular factors are involved in their mobilization and differentiation?", and "can these cells repair the damaged heart?" This review will address the state of current answers to these questions.

Emerging evidence suggests that several subpopulations of cardiac stem or progenitor cells (CPCs) reside within the adult heart. CPCs with the ability to differentiate into all the constituent cells in the adult heart including cardiac myocytes, vascular smooth muscle and endothelial cells have been identified. Valuable knowledge has been obtained from the large number of animal studies and a number of small clinical trials that have utilized a variety of adult stem cells for regenerating infarcted hearts. However, contradictory reports on the regenerative potential of the CPCs exist, and the mechanisms behind the reported hemodynamic effects are intensely debated. Besides directly replenishing cardiac tissue, CPCs could also function by stimulating angiogenesis and improving survival of existing cells by secretion of paracrine factors. With this review we suggest that a better understanding of CPC biology will be pivotal for progressing therapeutic cardiac regeneration. This includes an extended knowledge of the molecular mechanisms behind their mobilization, differentiation, survival and integration in the myocardium.

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References

  1. Anversa P, Rota M, Urbanek K, Hosoda T, Sonnenblick EH, Leri A, Kajstura J, Bolli R (2005) Myocardial aging — stem cell problem. Basic Res Cardiol 100:482–493

    Article  CAS  PubMed  Google Scholar 

  2. 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 107:1024–1032

    Article  PubMed  Google Scholar 

  3. Barile L,Messina E, Smith R, Leppo M, Abraham M,Pittenger M,Giacomello A, Marban E (2005) Engraftment, Migration And Functional Improvement In Ischemic Mouse Hearts Injected With Human Cardiosphere-derived Stem Cells. American Heart Association Scientifc Sessions

  4. 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 114:763–776

    Article  CAS  PubMed  Google Scholar 

  5. 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 344:1750–1757

    Article  CAS  PubMed  Google Scholar 

  6. Berry MF, Engler AJ,Woo YJ, Pirolli TJ, Bish LT, Jayasankar V,Morine KJ, Gardner TJ, Discher DE, Sweeney HL (2006) Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol 290:H2196–H2203

    Article  CAS  PubMed  Google Scholar 

  7. Cai C-L, Liang X, Shi Y, Chu P-H, Pfaff SL, Chen J, Evans S (2003) Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Developmental Cell 5:877

    Article  CAS  PubMed  Google Scholar 

  8. Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlstrom H, Lendahl U, Frisen J (2000) Generalized potential of adult neural stem cells. Science 288:1660–1663

    Article  CAS  PubMed  Google Scholar 

  9. Colter DC, Sekiya I, Prockop DJ (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA 98:7841–7845

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  11. Dan YY, Riehle KJ, Lazaro C, Teoh N, Haque J, Campbell JS, Fausto N (2006) Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci USA 103:9912–9917

    Article  CAS  PubMed  Google Scholar 

  12. Davis ME, Hsieh PC, Grodzinsky AJ, Lee RT (2005) Custom design of the cardiac microenvironment with biomaterials. Circ Res 97:8–5

    Article  CAS  PubMed  Google Scholar 

  13. Dawn B, Bolli R (2005) Adult bone marrow- derived cells: regenerative potential, plasticity, and tissue commitment. Basic Res Cardiol 100:494–503

    Article  CAS  PubMed  Google Scholar 

  14. 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 102:3766–3771

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  16. Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115:572–583

    CAS  PubMed  Google Scholar 

  17. Dodou E, Verzi MP, Anderson JP, Xu SM, Black BL (2004) Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development 131:3931–3942

    Article  CAS  PubMed  Google Scholar 

  18. Dooley DC, Oppenlander BK, Xiao M (2004) Analysis of primitive CD34- and CD34+ hematopoietic cells from adults: gain and loss of CD34 antigen by undifferentiated cells are closely linked to proliferative status in culture. Stem Cells 22:556–569

    Article  PubMed  Google Scholar 

  19. Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689

    Article  CAS  PubMed  Google Scholar 

  20. Fazel S, Cimini M, Chen L, Li S,Angoulvant D, Fedak P, Verma S, Weisel RD, Keating A, Li RK (2006) Cardioprotective c-kit cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 116:1865–1877

    Article  CAS  PubMed  Google Scholar 

  21. 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 279:1528–1530

    Article  CAS  PubMed  Google Scholar 

  22. French SW, Hoyer KK, Shen RR, Teitell MA (2002) Transdifferentiation and nuclear reprogramming in hematopoietic development and neoplasia. Immunol Rev 187:22–39

    Article  PubMed  Google Scholar 

  23. Glaser R, Lu MM, Narula N, Epstein JA (2002) Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts. Circulation 106:17–19

    Article  PubMed  Google Scholar 

  24. 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 183:1797–1806

    Article  CAS  PubMed  Google Scholar 

  25. Hamano K, Li TS, Kobayashi T, Hirata K, Yano M, Kohno M, Matsuzaki M (2002) Therapeutic angiogenesis induced by local autologous bone marrow cell implantation. Ann Thorac Surg 73:1210–1215

    Article  PubMed  Google Scholar 

  26. Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA (2002) The post-natal heart contains a myocardial stem cell population. FEBS Letters 530:239

    Article  CAS  PubMed  Google Scholar 

  27. Iijima Y, Nagai T, Mizukami M, Matsuura K, Ogura T, Wada H, Toko H, Akazawa H, Takano H, Nakaya H, Komuro I (2003) Beating is necessary for transdifferentiation of skeletal musclederived cells into cardiomyocytes. Faseb J 17:1361–1363

    CAS  PubMed  Google Scholar 

  28. Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107:1395–1402

    Article  CAS  PubMed  Google Scholar 

  29. Jackson KA, Mi T, Goodell MA (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. PNAS 96:14482–14486

    Article  CAS  PubMed  Google Scholar 

  30. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34

    Article  CAS  PubMed  Google Scholar 

  31. Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P (1998) Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci USA 95:8801–8805

    Article  CAS  PubMed  Google Scholar 

  32. Kajstura J, Rota M, Chimenti S, Limana F, Nascimbene A, Bearzi C, Hosoda T, Amano K, Mitchell T, Fiore G, Rotatori F, Cascapera S, Angelis A, Sonnenblick E,Urbanek K, Bolli R, Leri A,Anversa P (2005) Local Activation or Implantation of Cardiac Progenitor Cells Rescues Scarred Infarcted Myocardium Improving Cardiac Function. From the American Heart Association, Scientific sessions 2005

  33. Kawada H, Fujita J, Kinjo K,Matsuzaki Y, Tsuma M, Miyatake H,Muguruma Y, Tsuboi K, Itabashi Y, Ikeda Y, Ogawa S, Okano H, Hotta T, Ando K, Fukuda K (2004) Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood 104:3581–3587

    Article  CAS  PubMed  Google Scholar 

  34. 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 103:634–637

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. Klug MG, Soonpaa MH, Koh GY, Field LJ (1996) Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest 98:216–224

    Article  CAS  PubMed  Google Scholar 

  38. 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 7:430–436

    Article  CAS  PubMed  Google Scholar 

  39. Kofidis T,de Bruin JL,Yamane T,Balsam LB, Lebl DR, Swijnenburg R-J, Tanaka M,Weissman IL, Robbins RC (2004) Insulin- like growth factor promotes engraftment, differentiation, and functional improvement after transfer of embryonic stem cells for myocardial restoration. Stem Cells 22:1239–1245

    Article  CAS  PubMed  Google Scholar 

  40. Kofidis T, de Bruin JL, Yamane T, Tanaka M, Lebl DR, Swijnenburg R-J, Weissman IL, Robbins RC (2005) Stimulation of paracrine pathways with growth factors enhances embryonic stem cell engraftment and host-specific differentiation in the heart after ischemic myocardial injury. Circulation 111:2486–2493

    Article  CAS  PubMed  Google Scholar 

  41. 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 96:1039–1041

    Article  CAS  PubMed  Google Scholar 

  42. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’ Nature 438:685–680

    Article  PubMed  Google Scholar 

  43. 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 95:1191–1199

    Article  CAS  PubMed  Google Scholar 

  44. Kwon C,Han Z, Olson EN, Srivastava D (2005) MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. PNAS 102:18986–18991

    Article  CAS  PubMed  Google Scholar 

  45. Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856

    Article  CAS  PubMed  Google Scholar 

  46. Laflamme MA, Myerson D, Saffitz JE, Murry CE (2002) Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ Res 90:634–640

    Article  CAS  PubMed  Google Scholar 

  47. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653

    Article  CAS  PubMed  Google Scholar 

  48. Leri A, Kajstura J, Anversa P (2005) Identity deception: not a crime for a stem cell. Physiology 20:162–168

    Article  PubMed  Google Scholar 

  49. Li F, Wang X, Capasso JM, Gerdes AM (1996) Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 28:1737–1746

    Article  CAS  PubMed  Google Scholar 

  50. Li T-S, Hayashi M, Ito H, Furutani A, Murata T, Matsuzaki M, Hamano K (2005) Regeneration of infarcted myocardium by intramyocardial implantation of ex vivo transforming growth factor-β-preprogrammed bone marrow stem cells. Circulation 111:2438–2445

    Article  CAS  PubMed  Google Scholar 

  51. 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 102:8966–8971

    Article  CAS  PubMed  Google Scholar 

  52. Liu J, Hu Q, Wang Z, Xu C, Wang X, Gong G, Mansoor A, Lee J, Hou M, Zeng L, Zhang JR, Jerosch-Herold M, Guo T, Bache RJ, Zhang J (2004) Autologous stem cell transplantation for myocardial repair. Am J Physiol Heart Circ Physiol 287:H501–H511

    Article  CAS  PubMed  Google Scholar 

  53. Lyman SD, Jacobsen SE (1998) c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood 91:1101–1134

    CAS  PubMed  Google Scholar 

  54. 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 9:1195–1201

    Article  CAS  PubMed  Google Scholar 

  55. Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S, Goetsch SC, Gallardo TD, Garry DJ (2004) Persistent expression of the ATPbinding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Developmental Biology 265:262–275

    Article  CAS  PubMed  Google Scholar 

  56. 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 279:11384–11391

    Article  CAS  PubMed  Google Scholar 

  57. 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 167:351–363

    Article  CAS  PubMed  Google Scholar 

  58. 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 95:911–921

    Article  CAS  PubMed  Google Scholar 

  59. Min JY, Yang Y, Converso KL, Liu L, Huang Q, Morgan JP, Xiao YF (2002) Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. J Appl Physiol 92:288–296

    Article  PubMed  Google Scholar 

  60. Morrison SJ, Prowse KR, Ho P, Weissman IL (1996) Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5:207–216

    Article  CAS  PubMed  Google Scholar 

  61. Mouquet F, Pfister O, Jain M, Oikonomopoulos A, Ngoy S, Summer R, Fine A, Liao R (2005) Restoration of cardiac progenitor cells after myocardial infarction by self-proliferation and selective homing of bone marrow-derived stem cells. Circ Res 97:1090–1092

    Article  CAS  PubMed  Google Scholar 

  62. Muller P, Pfeiffer P, Koglin J, Schafers HJ, Seeland U, Janzen I, Urbschat S, Bohm M (2002) Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation 106:31–35

    Article  PubMed  Google Scholar 

  63. Nilsson SK, Hulspas R, Weier HU, Quesenberry PJ (1996) In situ detection of individual transplanted bone marrow cells using FISH on sections of paraffinembedded whole murine femurs. J Histochem Cytochem 44:1069–1074

    CAS  PubMed  Google Scholar 

  64. Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J, Taneera J, Fleischmann BK, Jacobsen SE (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10:494–501

    Article  CAS  PubMed  Google Scholar 

  65. 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 100:12313–12318

    Article  CAS  PubMed  Google Scholar 

  66. Okada H, Takemura G, Kosai K-i, Li Y, Takahashi T, Esaki M,Yuge K, Miyata S, Maruyama R, Mikami A, Minatoguchi S, Fujiwara T, Fujiwara H (2005) Postinfarction gene therapy against transforming growth factor- signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure. Circulation 111:2430–2437

    Article  CAS  PubMed  Google Scholar 

  67. Olmsted-Davis EA, Gugala Z, Camargo F, Gannon FH, Jackson K, Kienstra KA, Shine HD, Lindsey RW, Hirschi KK, Goodell MA, Brenner MK, Davis AR (2003) Primitive adult hematopoietic stem cells can function as osteoblast precursors. PNAS 100:15877–15882

    Article  CAS  PubMed  Google Scholar 

  68. 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 410:701–705

    Article  CAS  PubMed  Google Scholar 

  69. 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 98:10344–10349

    Article  CAS  PubMed  Google Scholar 

  70. 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 97:52–61

    Article  CAS  PubMed  Google Scholar 

  71. Planat-Benard V, Menard C, Andre M, Puceat M, Perez A, Garcia-Verdugo JM, Penicaud L, Casteilla L (2004) Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94:223–229

    Article  CAS  PubMed  Google Scholar 

  72. 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 346:5–15

    Article  PubMed  Google Scholar 

  73. Reinecke H, Zhang M, Bartosek T, Murry CE (1999) Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation 100:193–202

    CAS  PubMed  Google Scholar 

  74. Rijn MVD, Heimfeld S, Spangrude GJ, Weissman IL (1989) Mouse hematopoietic stem-cell antigen Sca-1 is a member of the Ly-6 antigen family. PNAS 86:4634–4638

    Article  PubMed  Google Scholar 

  75. Rombouts WJ, Ploemacher RE (2003) Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia 17:160–170

    Article  CAS  PubMed  Google Scholar 

  76. Rosenblatt-Velin N, Lepore MG, Cartoni C, Beermann F, Pedrazzini T (2005) FGF-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes. J Clin Invest 115:1724–1733

    Article  CAS  PubMed  Google Scholar 

  77. Rustom A, Saffrich R, Markovic I, Walther P, Gerdes H-H (2004) Nanotubular highways for intercellular organelle transport. Science 303:1007–1010

    Article  CAS  PubMed  Google Scholar 

  78. 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 1926

    Article  PubMed  Google Scholar 

  79. Silva J, Chambers I, Pollard S, Smith A (2006) Nanog promotes transfer of pluripotency after cell fusion. Nature 441:997

    Article  CAS  PubMed  Google Scholar 

  80. Soonpaa MH, Kim KK, Pajak L, Franklin M, Field LJ (1996) Cardiomyocyte DNA synthesis and binucleation during murine development. Am J Physiol 271:H2183–H2189

    CAS  PubMed  Google Scholar 

  81. Suzuki K, Murtuza B, Beauchamp JR, Brand NJ, Barton PJR, Varela-Carver A, Fukushima S, Coppen SR, Partridge TA, Yacoub MH (2004) Role of interleukin-β in acute inflammation and graft death after cell transplantation to the heart. Circulation 110:II-219–II-224

    Article  Google Scholar 

  82. Tam SK, Gu W, Mahdavi V, Nadal-Ginard B (1995) Cardiac myocyte terminal differentiation.Potential for cardiac regeneration. Ann N Y Acad Sci 752:72–79

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  84. Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, Yang YZ, Pan C, Ge J, Phillips MI (2004) Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117:3–10

    Article  CAS  PubMed  Google Scholar 

  85. 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 105:93–98

    Article  PubMed  Google Scholar 

  86. Tomita S, Mickle DA, Weisel RD, Jia ZQ, Tumiati LC, Allidina Y, Liu P, Li RK (2002) Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg 123:1132–1140

    Article  PubMed  Google Scholar 

  87. Tomita Y, Matsumura K,Wakamatsu Y, Matsuzaki Y, Shibuya I, Kawaguchi H, Ieda M, Kanakubo S, Shimazaki T, Ogawa S, Osumi N, Okano H, Fukuda K (2005) Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart. J Cell Biol 170:1135–1146

    Article  CAS  PubMed  Google Scholar 

  88. Uezumi A, Ojima K, Fukada S, Ikemoto M, Masuda S, Miyagoe-Suzuki Y, Takeda S (2006) Functional heterogeneity of side population cells in skeletal muscle. Biochem Biophys Res Commun 341:864–873

    Article  CAS  PubMed  Google Scholar 

  89. 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) From the Cover: Stem cell niches in the adult mouse heart. Proc Natl Acad Sci USA 103:9226–9231

    Article  CAS  PubMed  Google Scholar 

  90. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A, Kajstura J, Quaini E, Anversa P (2003) From The Cover: Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. PNAS 100:10440–10445

    Article  CAS  PubMed  Google Scholar 

  91. Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A,Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673

    Article  CAS  PubMed  Google Scholar 

  92. 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. PNAS 102:8692–8697

    Article  CAS  PubMed  Google Scholar 

  93. Wagers AJ, Weissman IL (2004) Plasticity of adult stem cells. Cell 116:639

    Article  CAS  PubMed  Google Scholar 

  94. 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 110:3213–3220

    Article  CAS  PubMed  Google Scholar 

  95. Xu M, Wani M, Dai YS, Wang J, Yan M, Ayub A, Ashraf M (2004) Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes. Circulation 110:2658–2665

    Article  PubMed  Google Scholar 

  96. Zhang S, Wang D, Estrov Z, Raj S, Willerson JT, Yeh ETH (2004) Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation 110:3803–3807

    Article  PubMed  Google Scholar 

  97. Zimmet JM, Hare JM (2005) Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy. Basic Res Cardiol 100:471–481

    Article  CAS  PubMed  Google Scholar 

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Correspondence to S. P. Sheikh MD, PhD.

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Lyngbæk, S., Schneider, M., Hansen, J.L. et al. Cardiac regeneration by resident stem and progenitor cells in the adult heart. Basic Res Cardiol 102, 101–114 (2007). https://doi.org/10.1007/s00395-007-0638-3

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  • DOI: https://doi.org/10.1007/s00395-007-0638-3

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