Stem Cell Based Cardioregeneration and Adipose Tissue

  • Atta BehfarEmail author
  • Andre Terzic


Cardiovascular medicine has recently implemented multiple pre-clinical and clinical trials intended to identify a feasible and safe approach for cell-based heart repair. In the myocardium, several recent studies demonstrate the benefit of ATSCs to include direct contribution to neovasculogenesis and de novo cardiogenesis, in addition to indirect paracrine action for cardioprotection, neoangiogenesis, and neuron spindle formation. Furthermore, treatment with ATSCs has demonstrated a diminished propensity for arrhythmogenic risk without any evidence for uncontrolled growth, systemic complications, or tumorigenic change. Engrafted adipose stem cells improves the myocardial function with the capacity for contribution both via direct differentiation and indirect regenerative paracrine signaling in the host myocardial microenvironment. Adipose tissue resource holds great promise in providing the raw stem cell material to generate therapeutic products in the treatment of cardiovascular disease. However, due to the heterogenous nature of derived stem cells, further evaluation is needed to delineate the mechanism of stem cell benefit within the myocardium and implement next generation approaches such as linage specification and combinatorial stem cell therapy.


Stem Cell Adult Stem Cell Bone Marrow Stem Cell Cardiac Stem Cell Adipose Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1.  1.
    Abdel-Latif A, Bolli R, Tleyjeh IM et al (2007) Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 167(10):989–997PubMedCrossRefGoogle Scholar
  2.  2.
    Alt E, Pinkernell K, Scharlau M et al (2010) Effect of freshly isolated autologous tissue resident stromal cells on cardiac function and perfusion following acute myocardial infarction. Int J Cardiol 144(1):26–35PubMedCrossRefGoogle Scholar
  3.  3.
    Ashjian PH, Elbarbary AS, Edmonds B et al (2003) In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg 111(6):1922–1931PubMedCrossRefGoogle Scholar
  4.  4.
    Askari AT, Unzek S, Popovic ZB et al (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362(9385):697–703PubMedCrossRefGoogle Scholar
  5.  5.
    Bai X, Alt E (2010) Myocardial regeneration potential of adipose tissue-derived stem cells. Biochem Biophys Res Commun 401(3):321–326PubMedCrossRefGoogle Scholar
  6.  6.
    Bartunek J, Vanderheyden M, Vandekerckhove B et al (2005) Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation 112(9 Suppl):I178–I183PubMedGoogle Scholar
  7.  7.
    Bartunek J, Dimmeler S, Drexler H et al (2006) The consensus of the task force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart. Eur Heart J 27(11):1338–1340PubMedCrossRefGoogle Scholar
  8.  8.
    Bartunek J, Behfar A, Vanderheyden M, Wijns W, Terzic A (2008) Mesenchymal stem cells and cardiac repair: principles and practice. J Cardiovasc Transl Res 1(2):115–119PubMedCrossRefGoogle Scholar
  9.  9.
    Bartunek J, Sherman W, Vanderheyden M, Fernandez-Aviles F, Wijns W, Terzic A (2009) Delivery of biologics in cardiovascular regenerative medicine. Clin Pharmacol Ther 85(5):548–552PubMedCrossRefGoogle Scholar
  10. 10.
    Bartunek J, Vanderheyden M, Hill J, Terzic A (2010) Cells as biologics for cardiac repair in ischaemic heart failure. Heart 96(10):792–800PubMedCrossRefGoogle Scholar
  11. 11.
    Bearzi C, Rota M, Hosoda T et al (2007) Human cardiac stem cells. Proc Natl Acad Sci USA 104(35):14068–14073PubMedCrossRefGoogle Scholar
  12. 12.
    Becker AJ, McCulloch CE, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454PubMedCrossRefGoogle Scholar
  13. 13.
    Behfar A, Terzic A (2006) Derivation of a cardiopoietic population from human mesenchymal stem cells yields ­cardiac progeny. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S78–S82PubMedCrossRefGoogle Scholar
  14. 14.
    Behfar A, Terzic A (2008) Mesenchymal stem cells: engineering regeneration. Clin Transl Sci 1(1):34–35PubMedCrossRefGoogle Scholar
  15. 15.
    Behfar A, Perez-Terzic C, Faustino RS et al (2007) Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J Exp Med 204(2):405–420PubMedCrossRefGoogle Scholar
  16. 16.
    Behfar A, Faustino RS, Arrell DK, Dzeja PP, Perez-Terzic C, Terzic A (2008) Guided stem cell cardiopoiesis: discovery and translation. J Mol Cell Cardiol 45(4):523–529PubMedCrossRefGoogle Scholar
  17. 17.
    Behfar A, Crespo-Diaz R, Nelson TJ, Terzic A, Gersh BJ (2010) Stem cells: clinical trials results the end of the beginning or the beginning of the end? Cardiovasc Hematol Disord Drug Targets 10(3):186–201PubMedCrossRefGoogle Scholar
  18. 18.
    Behfar A, Yamada S, Crespo-Diaz R et al (2010) Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol 56(9):721–34Google Scholar
  19. 19.
    Beitnes JO, Hopp E, Lunde K et al (2009) Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study. Heart 95(24):1983–1989PubMedCrossRefGoogle Scholar
  20. 20.
    Belonje AM, Voors AA, van Gilst WH et al (2008) Effects of erythropoietin after an acute myocardial infarction: rationale and study design of a prospective, randomized, clinical trial (HEBE III). Am Heart J 155(5):817–822PubMedCrossRefGoogle Scholar
  21. 21.
    Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6):763–776PubMedCrossRefGoogle Scholar
  22. 22.
    Bergmann O, Bhardwaj RD, Bernard S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102PubMedCrossRefGoogle Scholar
  23. 23.
    Bieback K, Hecker A, Kocaomer A et al (2009) Human alternatives to fetal bovine serum for the expansion of ­mesenchymal stromal cells from bone marrow. Stem Cells 27(9):2331–2341PubMedCrossRefGoogle Scholar
  24. 24.
    Braunwald E (2008) Biomarkers in heart failure. N Engl J Med 358(20):2148–2159PubMedCrossRefGoogle Scholar
  25. 25.
    Britten MB, Abolmaali ND, Assmus B et al (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(18):2212–2218PubMedCrossRefGoogle Scholar
  26. 26.
    Cai L, Johnstone BH, Cook TG et al (2009) IFATS collection: human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 27(1):230–237PubMedCrossRefGoogle Scholar
  27. 27.
    Caulfield JB, Leinbach R, Gold H (1976) The relationship of myocardial infarct size and prognosis. Circulation 53(3 Suppl):I141–I144PubMedGoogle Scholar
  28. 28.
    Chien KR, Domian IJ, Parker KK (2008) Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science 322(5907):1494–1497PubMedCrossRefGoogle Scholar
  29. 29.
    Cobo F, Concha A (2007) Application of microarray technology for microbial diagnosis in stem cell cultures: a review. Cytotherapy 9(1):53–59PubMedCrossRefGoogle Scholar
  30. 30.
    Cobo F, Cabrera C, Catalina P, Concha A (2006) General safety guidances in stem cell bank installations. Cytotherapy 8(1):47–56PubMedCrossRefGoogle Scholar
  31. 31.
    Cohnheim J (1867) Inflammation and sepsis. Pathol Anat Physiol Klin Med 40:1–79Google Scholar
  32. 32.
    Cousin B, Andre M, Arnaud E, Penicaud L, Casteilla L (2003) Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun 301(4):1016–1022PubMedCrossRefGoogle Scholar
  33. 33.
    Crespo-Diaz R, Behfar A, Perez-Terzic C, Bartunek J, Dietz AB, Terzic A (2011) Platelet lysate consisting of a natural repair proteome supports human mesenchymal stem cell proliferation and chromosomal stability.Cell Transplant. 2010 Nov 19. [Epub ahead of print]Google Scholar
  34. 34.
    Dawn B, Stein AB, Urbanek K et al (2005) Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci USA 102(10):3766–3771PubMedCrossRefGoogle Scholar
  35. 35.
    De Falco E, Porcelli D, Torella AR et al (2004) SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood 104(12):3472–3482PubMedCrossRefGoogle Scholar
  36. 36.
    Deuse T, Peter C, Fedak PW et al (2009) Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation 120(11 Suppl):S247–S254PubMedCrossRefGoogle Scholar
  37. 37.
    Dib N, McCarthy P, Campbell A et al (2005) Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplant 14(1):11–19PubMedCrossRefGoogle Scholar
  38. 38.
    Dib N, Dinsmore J, Lababidi Z et al (2009) One-year ­follow-up of feasibility and safety of the first U.S., randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic ­cardiomyopathy (CAuSMIC study). JACC Cardiovasc Interv 2(1):9–16PubMedCrossRefGoogle Scholar
  39. 39.
    Dietz AB, Padley DJ, Gastineau DA (2007) Infrastructure development for human cell therapy translation. Clin Pharmacol Ther 82(3):320–324PubMedCrossRefGoogle Scholar
  40. 40.
    Dill T, Schachinger V, Rolf A et al (2009) Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation ­myocardial infarction: results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study (REPAIR-AMI) cardiac magnetic resonance imaging substudy. Am Heart J 157(3):541–547PubMedCrossRefGoogle Scholar
  41. 41.
    Dimmeler S, Leri A (2008) Aging and disease as modifiers of efficacy of cell therapy. Circ Res 102(11):1319–1330PubMedCrossRefGoogle Scholar
  42. 42.
    Dimmeler S, Zeiher AM (2008) Cell therapy of acute ­myocardial infarction: open questions. Cardiology 113(3):155–160PubMedCrossRefGoogle Scholar
  43. 43.
    Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115(3):572–583PubMedGoogle Scholar
  44. 44.
    Dimmeler S, Burchfield J, Zeiher AM (2008) Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol 28(2):208–216PubMedCrossRefGoogle Scholar
  45. 45.
    Doerr HW, Cinatl J, Sturmer M, Rabenau HF (2003) Prions and orthopedic surgery. Infection 31(3):163–171PubMedGoogle Scholar
  46. 46.
    Engelmann MG, Theiss HD, Hennig-Theiss C et al (2006) Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Ele­vation Myocardial Infarction) trial. J Am Coll Cardiol 48(8):1712–1721PubMedCrossRefGoogle Scholar
  47. 47.
    Estes BT, Wu AW, Guilak F (2006) Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6. Arthritis Rheum 54(4):1222–1232PubMedCrossRefGoogle Scholar
  48. 48.
    Forrester JS, White AJ, Matsushita S, Chakravarty T, Makkar RR (2009) New paradigms of myocardial regeneration post-infarction: tissue preservation, cell environment, and pluripotent cell sources. JACC Cardiovasc Interv 2(1):1–8PubMedCrossRefGoogle Scholar
  49. 49.
    Fraser JK, Wulur I, Alfonso Z, Hedrick MH (2006) Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol 24(4):150–154PubMedCrossRefGoogle Scholar
  50. 50.
    Fraser JK, Zhu M, Wulur I, Alfonso Z (2008) Adipose-derived stem cells. Methods Mol Biol 449:59–67PubMedGoogle Scholar
  51. 51.
    Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116(6):769–778PubMedCrossRefGoogle Scholar
  52. 52.
    Gavira JJ, Perez-Ilzarbe M, Abizanda G et al (2006) A comparison between percutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction. Cardiovasc Res 71(4):744–753PubMedCrossRefGoogle Scholar
  53. 53.
    Ge J, Li Y, Qian J et al (2006) Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart 92(12):1764–1767PubMedCrossRefGoogle Scholar
  54. 54.
    Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A (2009) Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc 84(10):876–892PubMedCrossRefGoogle Scholar
  55. 55.
    Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5(5):362–369PubMedCrossRefGoogle Scholar
  56. 56.
    Gnecchi M, He H, Liang OD et al (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11(4):367–368PubMedCrossRefGoogle Scholar
  57. 57.
    Gregory CA, Reyes E, Whitney MJ, Spees JL (2006) Enhanced engraftment of mesenchymal stem cells in a cutaneous wound model by culture in allogenic species-specific serum and administration in fibrin constructs. Stem Cells 24(10):2232–2243PubMedCrossRefGoogle Scholar
  58. 58.
    Haider H, Lei Y, Ashraf M (2008) MyoCell, a cell-based, autologous skeletal myoblast therapy for the treatment of cardiovascular diseases. Curr Opin Mol Ther 10(6):611–621PubMedGoogle Scholar
  59. 59.
    Halvorsen YD, Franklin D, Bond AL et al (2001) Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng 7(6):729–741PubMedCrossRefGoogle Scholar
  60. 60.
    Hare JM, Chaparro SV (2008) Cardiac regeneration and stem cell therapy. Curr Opin Organ Transplant 13(5):536–542PubMedCrossRefGoogle Scholar
  61. 61.
    Hare JM, Traverse JH, Henry TD et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54(24):2277–2286PubMedCrossRefGoogle Scholar
  62. 62.
    Horwitz EM, Gordon PL, Koo WK et al (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci USA 99(13):8932–8937PubMedCrossRefGoogle Scholar
  63. 63.
    Hsieh PC, Segers VF, Davis ME et al (2007) Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 13(8):970–974PubMedCrossRefGoogle Scholar
  64. 64.
    Hunt SA, Baker DW, Chin MH et al (2001) ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary a report of the American College of Cardiology/American Heart Associa­tion Task Force on Practice Guidelines (Committee to revise the 1995 guidelines for the evaluation and mana­gement of heart failure): developed in collaboration with the Interna­tional Society for Heart and Lung Transplantation; endorsed by the Heart Failure Society of America. Circulation 104(24):2996–3007PubMedCrossRefGoogle Scholar
  65. 65.
    Hunt SA, Baker DW, Chin MH et al (2001) ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Associa­tion Task Force on Practice Guidelines (Committee to revise the 1995 guidelines for the evaluation and management of heart failure). J Am Coll Cardiol 38(7):2101–2113PubMedCrossRefGoogle Scholar
  66. 66.
    Janssens S (2010) Stem cells in the treatment of heart disease. Annu Rev Med 61:287–300PubMedCrossRefGoogle Scholar
  67. 67.
    Janssens S, Dubois C, Bogaert J et al (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367(9505):113–121PubMedCrossRefGoogle Scholar
  68. 68.
    Jennifer Manfrè MI (2007) An Unhealthy America: ­economic burden of chronic disease. The Milken Institute Review
  69. 69.
    Johnston PV, Sasano T, Mills K et al (2009) Engraftment, differentiation, and functional benefits of autologous ­cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation 120(12):1075–1083, 1077 p following 1083PubMedCrossRefGoogle Scholar
  70. 70.
    Kang HJ, Lee HY, Na SH et al (2006) Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Cir­culation 114(1 Suppl):I145–I151PubMedGoogle Scholar
  71. 71.
    Kang S, Yang YJ, Li CJ, Gao RL (2008) Effects of intracoronary autologous bone marrow cells on left ventricular function in acute myocardial infarction: a systematic review and meta-analysis for randomized controlled trials. Coron Artery Dis 19(5):327–335PubMedCrossRefGoogle Scholar
  72. 72.
    Labovsky V, Hofer EL, Feldman L et al (2010) Cardiomyo­genic differentiation of human bone marrow mesenchymal cells: role of cardiac extract from neonatal rat cardiomyocytes. Differentiation 79(2):93–101PubMedCrossRefGoogle Scholar
  73. 73.
    Lee RH, Pulin AA, Seo MJ et al (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5(1):54–63PubMedCrossRefGoogle Scholar
  74. 74.
    Leone AM, Rutella S, Bonanno G et al (2006) Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction. Int J Cardiol 111(2):202–208PubMedCrossRefGoogle Scholar
  75. 75.
    Leone AM, Valgimigli M, Giannico MB et al (2009) From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells. Eur Heart J 30(8):890–899PubMedCrossRefGoogle Scholar
  76. 76.
    Liao L, Anstrom KJ, Gottdiener JS et al (2007) Long-term costs and resource use in elderly participants with congestive heart failure in the Cardiovascular Health Study. Am Heart J 153(2):245–252PubMedCrossRefGoogle Scholar
  77. 77.
    Liechty KW, MacKenzie TC, Shaaban AF et al (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6(11):1282–1286PubMedCrossRefGoogle Scholar
  78. 78.
    Lipinski MJ, Biondi-Zoccai GG, Abbate A et al (2007) Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol 50(18):1761–1767PubMedCrossRefGoogle Scholar
  79. 79.
    Losordo DW, Schatz RA, White CJ et al (2007) Intramyocar­dial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115(25):3165–3172PubMedCrossRefGoogle Scholar
  80. 80.
    Lunde K, Solheim S, Aakhus S et al (2006) Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 355(12):1199–1209PubMedCrossRefGoogle Scholar
  81. 81.
    Mackensen A, Drager R, Schlesier M, Mertelsmann R, Lindemann A (2000) Presence of IgE antibodies to bovine serum albumin in a patient developing anaphylaxis after vaccination with human peptide-pulsed dendritic cells. Cancer Immunol Immunother 49(3):152–156PubMedCrossRefGoogle Scholar
  82. 82.
    Madonna R, De Caterina R (2010) Adipose tissue: a new source for cardiovascular repair. J Cardiovasc Med (Hagerstown) 11(2):71–80CrossRefGoogle Scholar
  83. 83.
    Mannello F, Tonti GA (2007) Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold! Stem Cells 25(7):1603–1609PubMedCrossRefGoogle Scholar
  84. 84.
    Marban E, Malliaras K (2010) Boot camp for mesenchymal stem cells. J Am Coll Cardiol 56(9):735–737PubMedCrossRefGoogle Scholar
  85. 85.
    Marelli D, Desrosiers C, El-alfy M, Kao RL, Chiu RC (1992) Cell transplantation for myocardial repair: an experimental approach. Cell Transplant 1(6):383–390PubMedGoogle Scholar
  86. 86.
    Martin-Rendon E, Brunskill S, Doree C et al (2008) Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev (4):CD006536Google Scholar
  87. 87.
    Martin-Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM (2008) Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J 29(15):1807–1818PubMedCrossRefGoogle Scholar
  88. 88.
    Mazo M, Planat-Benard V, Abizanda G et al (2008) Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction. Eur J Heart Fail 10(5):454–462PubMedCrossRefGoogle Scholar
  89. 89.
    Menasche P (2009) Cell-based therapy for heart disease: a clinically oriented perspective. Mol Ther 17(5):758–766PubMedCrossRefGoogle Scholar
  90. 90.
    Menasche P, Hagege AA, Vilquin JT et al (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41(7):1078–1083PubMedCrossRefGoogle Scholar
  91. 91.
    Menasche P, Alfieri O, Janssens S et al (2008) The Myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117(9):1189–1200PubMedCrossRefGoogle Scholar
  92. 92.
    Messina E, De Angelis L, Frati G et al (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95(9):911–921PubMedCrossRefGoogle Scholar
  93. 93.
    Meyer GP, Wollert KC, Lotz J et al (2006) Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 113(10):1287–1294PubMedCrossRefGoogle Scholar
  94. 94.
    Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A (2004) Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110(3):349–355PubMedCrossRefGoogle Scholar
  95. 95.
    Miyahara Y, Nagaya N, Kataoka M et al (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12(4):459–465PubMedCrossRefGoogle Scholar
  96. 96.
    Murry CE, Reinecke H, Pabon LM (2006) Regeneration gaps: observations on stem cells and cardiac repair. J Am Coll Cardiol 47(9):1777–1785PubMedCrossRefGoogle Scholar
  97. 97.
    Muul LM, Tuschong LM, Soenen SL et al (2003) Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial. Blood 101(7):2563–2569PubMedCrossRefGoogle Scholar
  98. 98.
    Nakagami H, Maeda K, Morishita R et al (2005) Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells. Arterioscler Thromb Vasc Biol 25(12):2542–2547PubMedCrossRefGoogle Scholar
  99. 99.
    Nelson TJ, Faustino RS, Chiriac A, Crespo-Diaz R, Behfar A, Terzic A (2008) CXCR4+/FLK-1+ biomarkers select a cardiopoietic lineage from embryonic stem cells. Stem Cells 26(6):1464–1473PubMedCrossRefGoogle Scholar
  100. 100.
    Nelson TJ, Behfar A, Yamada S, Martinez-Fernandez A, Terzic A (2009) Stem cell platforms for regenerative medicine. Clin Transl Sci 2(3):222–227PubMedCrossRefGoogle Scholar
  101. 101.
    Numaguchi Y, Sone T, Okumura K et al (2006) The impact of the capability of circulating progenitor cell to differ­entiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 114(1 Suppl):I114–I119PubMedGoogle Scholar
  102. 102.
    Opie SR, Dib N (2006) Surgical and catheter delivery of autologous myoblasts in patients with congestive heart failure. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S42–S45PubMedCrossRefGoogle Scholar
  103. 103.
    Orlic D, Kajstura J, Chimenti S et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705PubMedCrossRefGoogle Scholar
  104. 104.
    Passier R, van Laake LW, Mummery CL (2008) Stem-cell-based therapy and lessons from the heart. Nature 453(7193):322–329PubMedCrossRefGoogle Scholar
  105. 105.
    Perin EC, Lopez J (2006) Methods of stem cell delivery in cardiac diseases. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S110–S113PubMedCrossRefGoogle Scholar
  106. 106.
    Pfister O, Mouquet F, Jain M et al (2005) CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res 97(1):52–61PubMedCrossRefGoogle Scholar
  107. 107.
    Planat-Benard V, Menard C, Andre M et al (2004) Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94(2):223–229PubMedCrossRefGoogle Scholar
  108. 108.
    Quaini F, Urbanek K, Beltrami AP et al (2002) Chimerism of the transplanted heart. N Engl J Med 346(1):5–15PubMedCrossRefGoogle Scholar
  109. 109.
    Quevedo HC, Hatzistergos KE, Oskouei BN et al (2009) Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci USA 106(33):14022–14027PubMedCrossRefGoogle Scholar
  110. 110.
    Rafii S, Lyden D (2003) Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 9(6):702–712PubMedCrossRefGoogle Scholar
  111. 111.
    Rangappa S, Fen C, Lee EH, Bongso A, Sim EK (2003) Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg 75(3):775–779PubMedCrossRefGoogle Scholar
  112. 112.
    Rauscher FM, Goldschmidt-Clermont PJ, Davis BH et al (2003) Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108(4):457–463PubMedCrossRefGoogle Scholar
  113. 113.
    Rehman J, Traktuev D, Li J et al (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109(10):1292–1298PubMedCrossRefGoogle Scholar
  114. 114.
    Reinecke H, Minami E, Zhu WZ, Laflamme MA (2008) Cardiogenic differentiation and transdifferentiation of progenitor cells. Circ Res 103(10):1058–1071PubMedCrossRefGoogle Scholar
  115. 115.
    Reinisch A, Hofmann NA, Obenauf AC et al (2009) Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo. Blood 113(26):6716–6725PubMedCrossRefGoogle Scholar
  116. 116.
    Rosenzweig A (2006) Cardiac cell therapy – mixed results from mixed cells. N Engl J Med 355(12):1274–1277PubMedCrossRefGoogle Scholar
  117. 117.
    Schachinger V, Assmus B, Britten MB et al (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(8):1690–1699PubMedCrossRefGoogle Scholar
  118. 118.
    Schachinger V, Erbs S, Elsasser A et al (2006) Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 27(23):2775–2783PubMedCrossRefGoogle Scholar
  119. 119.
    Schachinger V, Erbs S, Elsasser A et al (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355(12):1210–1221PubMedCrossRefGoogle Scholar
  120. 120.
    Schenke-Layland K, Strem BM, Jordan MC et al (2009) Adipose tissue-derived cells improve cardiac function following myocardial infarction. J Surg Res 153(2):217–223PubMedCrossRefGoogle Scholar
  121. 121.
    Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S (2007) Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J 28(6):766–772PubMedCrossRefGoogle Scholar
  122. 122.
    Selvaggi TA, Walker RE, Fleisher TA (1997) Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. Blood 89(3):776–779PubMedGoogle Scholar
  123. 123.
    Setoguchi S, Glynn RJ, Avorn J, Mittleman MA, Levin R, Winkelmayer WC (2008) Improvements in long-term mortality after myocardial infarction and increased use of cardiovascular drugs after discharge: a 10-year trend analysis. J Am Coll Cardiol 51(13):1247–1254PubMedCrossRefGoogle Scholar
  124. 124.
    Shahdadfar A, Fronsdal K, Haug T, Reinholt FP, Brinchmann JE (2005) In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells 23(9):1357–1366PubMedCrossRefGoogle Scholar
  125. 125.
    Shamblott MJ, Axelman J, Wang S et al (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 95(23):13726–13731PubMedCrossRefGoogle Scholar
  126. 126.
    Sherman W (2007) Myocyte replacement therapy: skeletal myoblasts. Cell Transplant 16(9):971–975PubMedCrossRefGoogle Scholar
  127. 127.
    Sherman W, Martens TP, Viles-Gonzalez JF, Siminiak T (2006) Catheter-based delivery of cells to the heart. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S57–S64PubMedCrossRefGoogle Scholar
  128. 128.
    Shintani S, Murohara T, Ikeda H et al (2001) Mobilization of endothelial progenitor cells in patients with acute ­myocardial infarction. Circulation 103(23):2776–2779PubMedCrossRefGoogle Scholar
  129. 129.
    Siminiak T, Kalawski R, Fiszer D et al (2004) Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J 148(3):531–537PubMedCrossRefGoogle Scholar
  130. 130.
    Siminiak T, Burchardt P, Kurpisz M (2006) Postinfarction heart failure: surgical and trans-coronary-venous transplantation of autologous myoblasts. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S46–S51PubMedCrossRefGoogle Scholar
  131. 131.
    Smith RR, Barile L, Cho HC et al (2007) Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115(7):896–908PubMedCrossRefGoogle Scholar
  132. 132.
    Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M (2006) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 24(2):462–471PubMedCrossRefGoogle Scholar
  133. 133.
    Spees JL, Gregory CA, Singh H et al (2004) Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol Ther 9(5):747–756PubMedCrossRefGoogle Scholar
  134. 134.
    Srivastava D, Ivey KN (2006) Potential of stem-cell-based therapies for heart disease. Nature 441(7097):1097–1099PubMedCrossRefGoogle Scholar
  135. 135.
    Strauer BE, Brehm M, Zeus T et al (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106(15):1913–1918PubMedCrossRefGoogle Scholar
  136. 136.
    Talens-Visconti R, Bonora A, Jover R et al (2006) Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 12(36):5834–5845PubMedGoogle Scholar
  137. 137.
    Tang XL, Rokosh G, Sanganalmath SK et al (2010) Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation 121(2):293–305PubMedCrossRefGoogle Scholar
  138. 138.
    Tendera M, Wojakowski W (2009) Cell therapy – success does not come easy. Eur Heart J 30(6):640–641PubMedCrossRefGoogle Scholar
  139. 139.
    Thom T, Haase N, Rosamond W et al (2006) Heart disease and stroke statistics – 2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113(6):e85–e151PubMedCrossRefGoogle Scholar
  140. 140.
    Thompson CA, Nasseri BA, Makower J et al (2003) Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation. J Am Coll Cardiol 41(11):1964–1971PubMedCrossRefGoogle Scholar
  141. 141.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147PubMedCrossRefGoogle Scholar
  142. 142.
    Trainini JC, Lago N, de Paz J et al (2004) Myoblast transplantation for myocardial repair: a clinical case. J Heart Lung Transplant 23(4):503–505PubMedCrossRefGoogle Scholar
  143. 143.
    Traktuev DO, Merfeld-Clauss S, Li J et al (2008) A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial ­networks. Circ Res 102(1):77–85PubMedCrossRefGoogle Scholar
  144. 144.
    Tuschong L, Soenen SL, Blaese RM, Candotti F, Muul LM (2002) Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy. Hum Gene Ther 13(13):1605–1610PubMedCrossRefGoogle Scholar
  145. 145.
    Urbanek K, Torella D, Sheikh F et al (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA 102(24):8692–8697PubMedCrossRefGoogle Scholar
  146. 146.
    Valina C, Pinkernell K, Song YH et al (2007) Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J 28(21):2667–2677PubMedCrossRefGoogle Scholar
  147. 147.
    van Laake LW, Passier R, Doevendans PA, Mummery CL (2008) Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res 102(9):1008–1010PubMedCrossRefGoogle Scholar
  148. 148.
    van Ramshorst J, Bax JJ, Beeres SL et al (2009) Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 301(19):1997–2004PubMedCrossRefGoogle Scholar
  149. 149.
    Wagers AJ, Weissman IL (2004) Plasticity of adult stem cells. Cell 116(5):639–648PubMedCrossRefGoogle Scholar
  150. 150.
    Welt FG, Losordo DW (2006) Cell therapy for acute myocardial infarction: curb your enthusiasm? Circulation 113(10):1272–1274PubMedCrossRefGoogle Scholar
  151. 151.
    Worton RG, McCulloch EA, Till JE (1969) Physical separation of hemopoietic stem cells differing in their capacity for self-renewal. J Exp Med 130(1):91–103PubMedCrossRefGoogle Scholar
  152. 152.
    Yamada Y, Yokoyama S, Wang XD, Fukuda N, Takakura N (2007) Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow nonhematopoietic cells to differentiate into cardiomyocytes. Stem Cells 25(5):1326–1333PubMedCrossRefGoogle Scholar
  153. 153.
    Yamaguchi J, Kusano KF, Masuo O et al (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 107(9):1322–1328PubMedCrossRefGoogle Scholar
  154. 154.
    Zhu Y, Liu T, Song K, Fan X, Ma X, Cui Z (2008) Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem Funct 26(6):664–675PubMedCrossRefGoogle Scholar
  155. 155.
    Zhu XY, Zhang XZ, Xu L, Zhong XY, Ding Q, Chen YX (2009) Transplantation of adipose-derived stem cells overexpressing hHGF into cardiac tissue. Biochem Biophys Res Commun 379(4):1084–1090PubMedCrossRefGoogle Scholar
  156. 156.
    Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228PubMedCrossRefGoogle Scholar
  157. 157.
    Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of MedicineMayo Clinic Center for Regenerative MedicineRochesterUSA

Personalised recommendations