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Cardiac Versus Non-Cardiac Stem Cells to Repair the Heart: The Role of Autocrine/Paracrine Signals

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Advances in Stem Cell Research

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

The heart can grow and change to accommodate alterations in its workload in response to stress. Stress-induced pathological cardiac hypertrophy, characterized by an increase in the size of cardiac myocytes, is a major risk factor for the development of cardiomyopathies and heart failure. Restoration of damaged heart muscle through repair or regeneration is a promising strategy to cure cardiovascular diseases. The robust proliferative and differentiation capacity of stem cells holds the potential of an unlimited supply of functioning cardiomyocytes. A crucial issue in designing rational stem cell-based therapy approaches for cardiac diseases is the understanding of the exact mechanisms whereby each stem cell can affect the performance of the heart. Stem cells are self-renewing and can become functionally specialized cardiac cells with the proper milieu of locally acting growth and signaling factors. In this chapter, we review the current advancements in our understanding of how adult stem cells within the myocardium, such as cardiac stem cells, or derived from other tissues, such as mesenchymal stem cells, may contribute to the repair of the damaged heart. Moreover we describe how this process could be experimentally boosted for therapy, by manipulating local autocrine and paracrine molecules regulating endogenous stem cell regenerative potential.

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References

  1. Frey N, Olson EN (2003) Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65:45–79

    Article  PubMed  CAS  Google Scholar 

  2. Takimoto E, Kass DA (2007) Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 49(2):241–248

    Article  PubMed  CAS  Google Scholar 

  3. Seddon M, Looi YH, Shah AM (2007) Oxidative stress and redox signalling in cardiac hypertrophy and heart failure. Heart 93(8):903–907

    Article  PubMed  CAS  Google Scholar 

  4. Tendera M (2005) Epidemiology, treatment, and guidelines for the treatment of heart failure in Europe. Eur Heart J 7(J):J5–J9

    Article  Google Scholar 

  5. Zannad F, Briancon S, Juilliere Y, Mertes PM, Villemot JP, Alla F, Virion JM (1999) Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL Study. Epidemiologie de l’Insuffisance Cardiaque Avancee en Lorraine. J Am Coll Cardiol 33(3):734–742

    Article  PubMed  CAS  Google Scholar 

  6. Haldeman GA, Croft JB, Giles WH, Rashidee A (1999) Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J 137(2):352–360

    Article  PubMed  CAS  Google Scholar 

  7. Malek M (1999) Health economics of heart failure. Heart 82(Suppl 4):IV11–IV13

    Google Scholar 

  8. Heineke J, Molkentin JD (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 7(8):589–600

    Article  PubMed  CAS  Google Scholar 

  9. Kajstura J, Urbanek K, Perl S, Hosoda T, Zheng H, Ogorek B, Ferreira-Martins J, Goichberg P, Rondon-Clavo C, Sanada F, D’Amario D, Rota M, Del Monte F, Orlic D, Tisdale J, Leri A, Anversa P (2010) Cardiomyogenesis in the adult human heart. Circ Res 107(2):305–315

    Article  PubMed  CAS  Google Scholar 

  10. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102

    Google Scholar 

  11. Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473(7347):326–335

    Article  PubMed  CAS  Google Scholar 

  12. Krause K, Schneider C, Kuck KH, Jaquet K (2011) Stem cell therapy in cardiovascular disorders. Cardiovasc Ther 28(5):e101–e110

    Article  Google Scholar 

  13. Sharif F, Bartunek J, Vanderheyden M (2011) Adult stem cells in the treatment of acute myocardial infarction. Catheter Cardiovasc Interv 77(1):72–83

    Article  PubMed  Google Scholar 

  14. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  PubMed  CAS  Google Scholar 

  15. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872

    Article  PubMed  CAS  Google Scholar 

  16. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317

    Article  PubMed  CAS  Google Scholar 

  17. Wong SS, Bernstein HS (2010) Cardiac regeneration using human embryonic stem cells: producing cells for future therapy. Regen Med 5(5):763–775

    Article  PubMed  Google Scholar 

  18. Nelson TJ, Martinez-Fernandez A, Terzic A (2010) Induced pluripotent stem cells: developmental biology to regenerative medicine. Nat Rev Cardiol 7(12):700–710

    PubMed  Google Scholar 

  19. Leeper NJ, Hunter AL, Cooke JP (2010) Stem cell therapy for vascular regeneration: adult, embryonic, and induced pluripotent stem cells. Circulation 122(5):517–526

    Article  PubMed  Google Scholar 

  20. Ausoni S, Sartore S (2009) The cardiovascular unit as a dynamic player in disease and regeneration. Trends Mol Med 15(12):543–552

    Article  PubMed  Google Scholar 

  21. 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(6):763–776

    Article  PubMed  CAS  Google Scholar 

  22. Smart N, Bollini S, Dube KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (2011) De novo cardiomyocytes from within the activated adult heart after injury. Nature 474(7353):640–644

    Article  PubMed  CAS  Google Scholar 

  23. Avitabile D, Crespi A, Brioschi C, Parente V, Toietta G, Devanna P, Baruscotti M, Truffa S, Scavone A, Rusconi F, Biondi A, D’Alessandra Y, Vigna E, Difrancesco D, Pesce M, Capogrossi MC, Barbuti A (2011) Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process. Am J Physiol Heart Circ Physiol 300(5):H1875–H1884

    Article  PubMed  CAS  Google Scholar 

  24. Fortini C, Toffoletto B, Fucili A, Puppato E, Olivares A, Beltrami AP, Fiorelli V, Bergamin N, Cesselli D, Morelli C, Francolini G, Ferrari R, Beltrami CA (2011) Circulating stem cell vary with NYHA stage in heart failure patients. J Cell Mol Med 15(8):1726–1736

    Article  PubMed  CAS  Google Scholar 

  25. Cesselli D, Beltrami AP, D’Aurizio F, Marcon P, Bergamin N, Toffoletto B, Pandolfi M, Puppato E, Marino L, Signore S, Livi U, Verardo R, Piazza S, Marchionni L, Fiorini C, Schneider C, Hosoda T, Rota M, Kajstura J, Anversa P, Beltrami CA, Leri A (2011) Effects of age and heart failure on human cardiac stem cell function. Am J Pathol 179(1):349–366

    Article  PubMed  CAS  Google Scholar 

  26. Lionetti V, Cecchini M, Ventura C (2011) Nanomechanics to drive stem cells in injured tissues: insights from current research and future perspectives. Stem Cells Dev 20(4):561–568

    Article  PubMed  Google Scholar 

  27. Ventura C, Cavallini C, Bianchi F, Cantoni S (2008) Stem cells and cardiovascular repair: a role for natural and synthetic molecules harboring differentiating and paracrine logics. Cardiovasc Hematol Agents Med Chem 6(1):60–68

    Article  PubMed  CAS  Google Scholar 

  28. Lisi A, Ledda M, de Carlo F, Pozzi D, Messina E, Gaetani R, Chimenti I, Barile L, Giacomello A, D’Emilia E, Giuliani L, Foletti A, Patti A, Vulcano A, Grimaldi S (2008) Ion cyclotron resonance as a tool in regenerative medicine. Electromagn Biol Med 27(2):127–133

    Article  PubMed  CAS  Google Scholar 

  29. Ventura C, Maioli M, Asara Y, Santoni D, Mesirca P, Remondini D, Bersani F (2005) Turning on stem cell cardiogenesis with extremely low frequency magnetic fields. Faseb J 19(1):155–157

    PubMed  CAS  Google Scholar 

  30. Lionetti V, Fittipaldi A, Agostini S, Giacca M, Recchia FA, Picano E (2009) Enhanced caveolae-mediated endocytosis by diagnostic ultrasound in vitro. Ultrasound Med Biol 35(1):136–143

    Article  PubMed  Google Scholar 

  31. Martino CF, Perea H, Hopfner U, Ferguson VL, Wintermantel E (2010) Effects of weak static magnetic fields on endothelial cells. Bioelectromagnetics 31(4):296–301

    PubMed  CAS  Google Scholar 

  32. Okano H, Onmori R, Tomita N, Ikada Y (2006) Effects of a moderate-intensity static magnetic field on VEGF-A stimulated endothelial capillary tubule formation in vitro. Bioelectromagnetics 27(8):628–640

    Article  PubMed  CAS  Google Scholar 

  33. Murray JC, Farndale RW (1985) Modulation of collagen production in cultured fibroblasts by a low-frequency, pulsed magnetic field. Biochim Biophys Acta 838(1):98–105

    Article  PubMed  CAS  Google Scholar 

  34. Lionetti V, Cantoni S, Cavallini C, Bianchi F, Valente S, Frascari I, Olivi E, Aquaro GD, Bonavita F, Scarlata I, Maioli M, Vaccari V, Tassinari R, Bartoli A, Recchia FA, Pasquinelli G, Ventura C (2010) Hyaluronan mixed esters of butyric and retinoic acid affording myocardial survival and repair without stem cell transplantation. J Biol Chem 285(13):9949–9961

    Article  PubMed  CAS  Google Scholar 

  35. Ventura C, Maioli M, Asara Y, Santoni D, Scarlata I, Cantoni S, Perbellini A (2004) Butyric and retinoic mixed ester of hyaluronan: a novel differentiating glycoconjugate affording a high throughput of cardiogenesis in embryonic stem cells. J Biol Chem 279(22):23574–23579

    Article  PubMed  CAS  Google Scholar 

  36. Maioli M, Santaniello S, Montella A, Bandiera P, Cantoni S, Cavallini C, Bianchi F, Lionetti V, Rizzolio F, Marchesi I, Bagella L, Ventura C (2010) Hyaluronan esters drive Smad gene expression and signaling enhancing cardiogenesis in mouse embryonic and human mesenchymal stem cells. PLoS ONE 5(11):e15151

    Article  PubMed  CAS  Google Scholar 

  37. Ventura C, Cantoni S, Bianchi F, Lionetti V, Cavallini C, Scarlata I, Foroni L, Maioli M, Bonsi L, Alviano F, Fossati V, Bagnara GP, Pasquinelli G, Recchia FA, Perbellini A (2007) Hyaluronan mixed esters of butyric and retinoic acid drive cardiac and endothelial fate in term placenta human mesenchymal stem cells and enhance cardiac repair in infarcted rat hearts. J Biol Chem 282(19):14243–14252

    Article  PubMed  CAS  Google Scholar 

  38. Simioniuc A, Campan M, Lionetti V, Marinelli M, Aquaro GD, Cavallini C, Valente S, Di Silvestre D, Cantoni S, Bernini F, Simi C, Pardini S, Mauri P, Neglia D, Ventura C, Pasquinelli G, Recchia FA (2011) Placental stem cells pre-treated with a hyaluronan mixed ester of butyric and retinoic acid to cure infarcted pig hearts: a multimodal study. Cardiovasc Res 90(3):546–556

    Article  PubMed  CAS  Google Scholar 

  39. Limana F, Esposito G, D’Arcangelo D, Di Carlo A, Romani S, Melillo G, Mangoni A, Bertolami C, Pompilio G, Germani A, Capogrossi MC (2011) HMGB1 attenuates cardiac remodelling in the failing heart via enhanced cardiac regeneration and miR-206-mediated inhibition of TIMP-3. PLoS ONE 6(6):e19845

    Article  PubMed  CAS  Google Scholar 

  40. Forini F, Lionetti V, Ardehali H, Pucci A, Cecchetti F, Ghanefar M, Nicolini G, Ichikawa Y, Nannipieri M, Recchia FA, Iervasi G (2011) Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac remodelling in rats. J Cell Mol Med 15(3):514–524

    Article  PubMed  CAS  Google Scholar 

  41. Nagaya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y, Fujii T, Uematsu M, Ohgushi H, Yamagishi M, Tokudome T, Mori H, Miyatake K, Kitamura S (2005) Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112(8):1128–1135

    Article  PubMed  Google Scholar 

  42. 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(2):326–338

    PubMed  CAS  Google Scholar 

  43. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084

    Article  PubMed  CAS  Google Scholar 

  44. Markel TA, Wang Y, Herrmann JL, Crisostomo PR, Wang M, Novotny NM, Herring CM, Tan J, Lahm T, Meldrum DR (2008) VEGF is critical for stem cell-mediated cardioprotection and a crucial paracrine factor for defining the age threshold in adult and neonatal stem cell function. Am J Physiol Heart Circ Physiol 295(6):H2308–H2314

    Article  PubMed  CAS  Google Scholar 

  45. Chimenti I, Smith RR, Li TS, Gerstenblith G, Messina E, Giacomello A, Marban E (2010) Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res 106(5):971–980

    Article  PubMed  CAS  Google Scholar 

  46. Shabbir A, Zisa D, Lin H, Mastri M, Roloff G, Suzuki G, Lee T (2010) Activation of host tissue trophic factors through JAK-STAT3 signaling: a mechanism of mesenchymal stem cell-mediated cardiac repair. Am J Physiol Heart Circ Physiol 299(5):H1428–H1438

    Article  PubMed  CAS  Google Scholar 

  47. Gnecchi M, Zhang Z, Ni A, Dzau VJ (2008) Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 103(11):1204–1219

    Article  PubMed  CAS  Google Scholar 

  48. Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ (2011) Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 50(2):280–289

    Article  PubMed  CAS  Google Scholar 

  49. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ (2005) Paracrine action accounts for marked protection of ischemic heart by AKT-modified mesenchymal stem cells. Nat Med 11(4):367–368

    Article  PubMed  CAS  Google Scholar 

  50. Simpson DL, Boyd NL, Kaushal S, Stice SL, Dudley SC Jr (2012) Use of human embryonic stem cell derived-mesenchymal cells for cardiac repair. Biotechnol Bioeng 109(1):274–283

    Article  PubMed  CAS  Google Scholar 

  51. Timmers L, Lim SK, Hoefer IE, Arslan F, Lai RC, van Oorschot AA, Goumans MJ, Strijder C, Sze SK, Choo A, Piek JJ, Doevendans PA, Pasterkamp G, de Kleijn DP (2011) Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res 6(3):206–214

    Article  PubMed  Google Scholar 

  52. See F, Seki T, Psaltis PJ, Sondermeijer HP, Gronthos S, Zannettino AC, Govaert KM, Schuster MD, Kurlansky PA, Kelly DJ, Krum H, Itescu S (2011) Therapeutic effects of human STRO-3-selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia. J Cell Mol Med 25:1533–1542

    Google Scholar 

  53. Schittini AV, Celedon PF, Stimamiglio MA, Krieger M, Hansen P, da Costa FD, Goldenberg S, Dallagiovanna B, Correa A (2010) Human cardiac explant-conditioned medium: soluble factors and cardiomyogenic effect on mesenchymal stem cells. Exp Biol Med (Maywood) 235(8):1015–1024

    Article  CAS  Google Scholar 

  54. Kubal C, Sheth K, Nadal-Ginard B, Galinanes M (2006) Bone marrow cells have a potent anti-ischemic effect against myocardial cell death in humans. J Thorac Cardiovasc Surg 132(5):1112–1118

    Article  PubMed  Google Scholar 

  55. Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, Mu H, Melo LG, Pratt RE, Ingwall JS, Dzau VJ (2006) Evidence supporting paracrine hypothesis for AKT-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. Faseb J 20(6):661–669

    Article  PubMed  CAS  Google Scholar 

  56. 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(5):678–685

    Article  PubMed  CAS  Google Scholar 

  57. Ohnishi S, Yasuda T, Kitamura S, Nagaya N (2007) Effect of hypoxia on gene expression of bone marrow-derived mesenchymal stem cells and mononuclear cells. Stem Cells 25(5):1166–1177

    Article  PubMed  CAS  Google Scholar 

  58. 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(12):1543–1549

    Article  PubMed  CAS  Google Scholar 

  59. Jiang S, Haider H, Idris NM, Salim A, Ashraf M (2006) Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ Res 99(7):776–784

    Article  PubMed  CAS  Google Scholar 

  60. Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, Yamagishi M, Mori H, Kangawa K, Kitamura S (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287(6):H2670–H2676

    Article  PubMed  CAS  Google Scholar 

  61. 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(6):1132–1140

    Article  PubMed  Google Scholar 

  62. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A, Kajstura J, Quaini E, Anversa P (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci U S A 100(18):10440–10445

    Article  PubMed  CAS  Google Scholar 

  63. Cossu G, Bianco P (2003) Mesoangioblasts—vascular progenitors for extravascular mesodermal tissues. Curr Opin Genet Dev 13(5):537–542

    Article  PubMed  CAS  Google Scholar 

  64. 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 U S A 102(32):11474–11479

    Article  PubMed  CAS  Google Scholar 

  65. Kolf CM, Cho E, Tuan RS (2007) Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 9(1):204

    Article  PubMed  CAS  Google Scholar 

  66. Alfaro MP, Pagni M, Vincent A, Atkinson J, Hill MF, Cates J, Davidson JM, Rottman J, Lee E, Young PP (2008) The Wnt modulator sFRP2 enhances mesenchymal stem cell engraftment, granulation tissue formation and myocardial repair. Proc Natl Acad Sci U S A 105(47):18366–18371

    Article  PubMed  Google Scholar 

  67. Vinciguerra M, Musaro A, Rosenthal N (2010) Regulation of muscle atrophy in aging and disease. Adv Exp Med Biol 694:211–233

    Article  PubMed  CAS  Google Scholar 

  68. Foncea R, Andersson M, Ketterman A, Blakesley V, Sapag-Hagar M, Sugden PH, LeRoith D, Lavandero S (1997) Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes. J Biol Chem 272(31):19115–19124

    Article  PubMed  CAS  Google Scholar 

  69. Takahashi M, Li TS, Suzuki R, Kobayashi T, Ito H, Ikeda Y, Matsuzaki M, Hamano K (2006) Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. Am J Physiol Heart Circ Physiol 291(2):H886–H893

    Article  PubMed  CAS  Google Scholar 

  70. Lim SY, Kim YS, Ahn Y, Jeong MH, Hong MH, Joo SY, Nam KI, Cho JG, Kang PM, Park JC (2006) The effects of mesenchymal stem cells transduced with AKT in a porcine myocardial infarction model. Cardiovasc Res 70(3):530–542

    Article  PubMed  CAS  Google Scholar 

  71. Xu M, Uemura R, Dai Y, Wang Y, Pasha Z, Ashraf M (2007) In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function. J Mol Cell Cardiol 42(2):441–448

    Article  PubMed  CAS  Google Scholar 

  72. Uemura R, Xu M, Ahmad N, Ashraf M (2006) Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res 98(11):1414–1421

    Article  PubMed  CAS  Google Scholar 

  73. Haider H, Jiang S, Idris NM, Ashraf M (2008) IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair. Circ Res 103(11):1300–1308

    Article  PubMed  CAS  Google Scholar 

  74. 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 U S A 102(25):8966–8971

    Article  PubMed  CAS  Google Scholar 

  75. 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(7):663–673

    Article  PubMed  CAS  Google Scholar 

  76. D’Amario D, Cabral-Da-Silva MC, Zheng H, Fiorini C, Goichberg P, Steadman E, Ferreira-Martins J, Sanada F, Piccoli M, Cappetta D, D’Alessandro DA, Michler RE, Hosoda T, Anastasia L, Rota M, Leri A, Anversa P, Kajstura J (2011) Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration. Circ Res 108(12):1467–1481

    Article  PubMed  CAS  Google Scholar 

  77. Gonzalez A, Rota M, Nurzynska D, Misao Y, Tillmanns J, Ojaimi C, Padin-Iruegas ME, Muller P, Esposito G, Bearzi C, Vitale S, Dawn B, Sanganalmath SK, Baker M, Hintze TH, Bolli R, Urbanek K, Hosoda T, Anversa P, Kajstura J, Leri A (2008) Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circ Res 102(5):597–606

    Article  PubMed  CAS  Google Scholar 

  78. Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, Zias E, Walsh K, Rosenzweig A, Sussman MA, Urbanek K, Nadal-Ginard B, Kajstura J, Anversa P, Leri A (2004) Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 94(4):514–524

    Article  PubMed  CAS  Google Scholar 

  79. Tillmanns J, Rota M, Hosoda T, Misao Y, Esposito G, Gonzalez A, Vitale S, Parolin C, Yasuzawa-Amano S, Muraski J, De Angelis A, Lecapitaine N, Siggins RW, Loredo M, Bearzi C, Bolli R, Urbanek K, Leri A, Kajstura J, Anversa P (2008) Formation of large coronary arteries by cardiac progenitor cells. Proc Natl Acad Sci U S A 105(5):1668–1673

    Article  PubMed  Google Scholar 

  80. Santini MP, Tsao L, Monassier L, Theodoropoulos C, Carter J, Lara-Pezzi E, Slonimsky E, Salimova E, Delafontaine P, Song YH, Bergmann M, Freund C, Suzuki K, Rosenthal N (2007) Enhancing repair of the mammalian heart. Circ Res 100(12):1732–1740

    Article  PubMed  CAS  Google Scholar 

  81. Santini MP, Lexow J, Borsellino G, Slonimski E, Zarrinpashneh E, Poggioli T, Rosenthal N (2011) IGF-1Ea induces vessel formation after injury and mediates bone marrow and heart cross-talk through the expression of specific cytokines. Biochem Biophys Res Commun 410(2):201–207

    Article  PubMed  CAS  Google Scholar 

  82. Vinciguerra M, Santini MP, Claycomb WC, Ladurner AG, Rosenthal N (2009) Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity. Aging (Albany N Y) 2(1):43–62

    Google Scholar 

  83. Vinciguerra M, Santini MP, Martinez C, Pazienza V, Claycomb WC, Giuliani A, Rosenthal N (2012) mIGF-1/JNK1/SirT1 signaling confers protection against oxidative stress in the heart. Aging Cell 11:139–149

    Google Scholar 

  84. Pelosi L, Giacinti C, Nardis C, Borsellino G, Rizzuto E, Nicoletti C, Wannenes F, Battistini L, Rosenthal N, Molinaro M, Musaro A (2007) Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines. Faseb J 21(7):1393–1402

    Article  PubMed  CAS  Google Scholar 

  85. Musarò A, Giacinti C, Borsellino G, Dobrowolny G, Pelosi L, Cairns L, Ottolenghi S, Cossu G, Bernardi G, Battistini L, Molinaro M, Rosenthal N (2004) Stem cell-mediated muscle regeneration is enhanced by local isoform of insulin-like growth factor 1. Proc Natl Acad Sci U S A 101(5):1206–1210

    Google Scholar 

  86. de Wert G, Mummery C (2003) Human embryonic stem cells: research, ethics and policy. Hum Reprod 18(4):672–682

    Article  PubMed  Google Scholar 

  87. Juengst E, Fossel M (2000) The ethics of embryonic stem cells—now and forever, cells without end. JAMA 284(24):3180–3184

    Article  PubMed  CAS  Google Scholar 

  88. Cao F, Lin S, Xie X, Ray P, Patel M, Zhang X, Drukker M, Dylla SJ, Connolly AJ, Chen X, Weissman IL, Gambhir SS, Wu JC (2006) In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation 113(7):1005–1014

    Article  PubMed  Google Scholar 

  89. Chaudhry GR, Fecek C, Lai MM, Wu WC, Chang M, Vasquez A, Pasierb M, Trese MT (2009) Fate of embryonic stem cell derivatives implanted into the vitreous of a slow retinal degenerative mouse model. Stem Cells Dev 18(2):247–258

    Article  PubMed  CAS  Google Scholar 

  90. Draper JS, Pigott C, Thomson JA, Andrews PW (2002) Surface antigens of human embryonic stem cells: changes upon differentiation in culture. J Anat 200(Pt 3):249–258

    Article  PubMed  CAS  Google Scholar 

  91. Zimmermann WH (2011) Embryonic and embryonic-like stem cells in heart muscle engineering. J Mol Cell Cardiol 50(2):320–326

    Article  PubMed  CAS  Google Scholar 

  92. Behfar A, Perez-Terzic C, Faustino RS, Arrell DK, Hodgson DM, Yamada S, Puceat M, Niederlander N, Alekseev AE, Zingman LV, Terzic A (2007) Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J Exp Med 204(2):405–420

    Article  PubMed  CAS  Google Scholar 

  93. Crisostomo PR, Abarbanell AM, Wang M, Lahm T, Wang Y, Meldrum DR (2008) Embryonic stem cells attenuate myocardial dysfunction and inflammation after surgical global ischemia via paracrine actions. Am J Physiol Heart Circ Physiol 295(4):H1726–H1735

    Article  PubMed  CAS  Google Scholar 

  94. Banquet S, Gomez E, Nicol L, Edwards-Levy F, Henry JP, Cao R, Schapman D, Dautreaux B, Lallemand F, Bauer F, Cao Y, Thuillez C, Mulder P, Richard V, Brakenhielm E (2011) Arteriogenic therapy by intramyocardial sustained delivery of a novel growth factor combination prevents chronic heart failure. Circulation 124(9):1059–1069

    Article  PubMed  Google Scholar 

  95. Ellison GM, Torella D, Dellegrottaglie S, Perez-Martinez C, Perez de Prado A, Vicinanza C, Purushothaman S, Galuppo V, Iaconetti C, Waring CD, Smith A, Torella M, Cuellas Ramon C, Gonzalo-Orden JM, Agosti V, Indolfi C, Galinanes M, Fernandez-Vazquez F, Nadal-Ginard B (2011) Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol 58(9):977–986

    Article  PubMed  CAS  Google Scholar 

  96. Timmers L, Lim SK, Arslan F, Armstrong JS, Hoefer IE, Doevendans PA, Piek JJ, El Oakley RM, Choo A, Lee CN, Pasterkamp G, de Kleijn DP (2007) Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res 1(2):129–137

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Campus A. Buzzati-Traverso, Monterotondo, Italy

    Manlio Vinciguerra & Nadia Rosenthal

  2. Istituto EuroMEditerraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy

    Manlio Vinciguerra

  3. Laboratory of Medical Science, Scuola Superiore Sant’Anna, Institute of Life Sciences, Pisa, Italy

    Vincenzo Lionetti

  4. Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, University of Bologna, Bologna, Italy

    Vincenzo Lionetti & Carlo Ventura

  5. Cardiovascular Department, S. Orsola–Malpighi Hospital, University of Bologna, Bologna, Italy

    Carlo Ventura

  6. Australian Regenerative Medicine Institute (ARMI), Monash University, Melbourne, VIC, Australia

    Nadia Rosenthal

Authors
  1. Manlio Vinciguerra
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  2. Vincenzo Lionetti
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  3. Carlo Ventura
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  4. Nadia Rosenthal
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Corresponding author

Correspondence to Manlio Vinciguerra .

Editor information

Editors and Affiliations

  1. Royan Institute, Department of Developmental Biology, University of Science and Culture, PO Box 19395-4644, Tehran, Iran

    Hossein Baharvand

  2. , Regenerative Medicine, Royan Institute for Stem Cell Biology an, P.O. Box: 19395-4644, Tehran, Iran

    Nasser Aghdami

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Vinciguerra, M., Lionetti, V., Ventura, C., Rosenthal, N. (2012). Cardiac Versus Non-Cardiac Stem Cells to Repair the Heart: The Role of Autocrine/Paracrine Signals. In: Baharvand, H., Aghdami, N. (eds) Advances in Stem Cell Research. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-940-2_17

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