Article thumbnail

Cardiac regeneration: different cells same goal

By Phil Barnett and Maurice J. B. van den Hoff


Cardiovascular diseases are the leading cause of mortality, morbidity, hospitalization and impaired quality of life. In most, if not all, pathologic cardiac ischemia ensues triggering a succession of events leading to massive death of cardiomyocytes, fibroblast and extracellular matrix accumulation, cardiomyocyte hypertrophy which culminates in heart failure and eventually death. Though current pharmacological treatment is able to delay the succession of events and as a consequence the development of heart failure, the only currently available and effective treatment of end-stage heart failure is heart transplantation. However, donor heart availability and immunorejection upon transplantation seriously limit the applicability. Cardiac regeneration could provide a solution, making real a dream of both scientist and clinician in the previous century and ending an ongoing challenge for this century. In this review, we present a basic overview of the various cell types that have been used in both the clinical and research setting with respect to myocardial differentiation

Topics: Review Article
Publisher: Springer-Verlag
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2007). 49:723–732 729 123SSEA-4 are not essential for human ESC pluripotency.
  2. (2008). A factor underlying late-phase arrhythmogenicity after cell therapy to the heart: global downregulation of Connexin43 in the host myocardium after skeletal myoblast transplantation. Circulation 118:S138–S144
  3. (2010). A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity.
  4. (2010). Abstract 12225: first-in-man experience with intracoronary infusion of adipose-derived regenerative cells in the treatment of patients with ST-elevation myocardial infarction: the Apollo Trial. Circulation 122:A12225
  5. (1971). Application of marrow grafts in human disease.
  6. (2008). Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review.
  7. (2006). Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res 98:1414–1421
  8. Campeau RJ et al (2007) Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction.
  9. (2008). Cardiac mesoangioblasts are committed, self-renewable progenitors, associated with small vessels of juvenile mouse ventricle.
  10. (2010). Cardiac progenitor cells and bone marrow-derived very small embryonic-like stem cells for cardiac repair after myocardiali.
  11. (2010). Cardiac regeneration: still a 21st century challenge in search for cardiac progenitors from stem cells and embryos.
  12. (1996). Cardiomyocyte DNA synthesis and binucleation during murine development.
  13. (2010). Cardiomyogenic potential of C-kit(?)-expressing cells derived from neonatal and adult mouse hearts.
  14. Caspi O et al (2010) In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies.
  15. (2007). Cell Initiative
  16. (2009). Cell therapy of acute myocardial infarction: open questions.
  17. (2010). Clinical outcome 2 years after intracoronary administration of bone Marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail 3:89–96
  18. (1986). Cornelisse CJ
  19. Cornetta K et al (2007) Suppression of hepatocyte growth factor production impairs the ability of adipose-derived stem cells to promote ischemic tissue revascularization.
  20. Crippa S et al (2009) Human cardiac mesoangioblasts isolated from hypertrophic cardiomyopathies are greatly reduced in proliferation and differentiation potency.
  21. (2010). Derivation of multipotent progenitors from human circulating CD14? monocytes. Exp Hematol 38:557–
  22. (2007). Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse.
  23. (1997). Developmental changes in rat cardiac DNA, RNA and protein tissue base: implications for the interpretation of changes in gene expression.
  24. (2009). Direct injection of autologous mesenchymal stromal cells improves myocardial function.
  25. (2010). Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.
  26. (2009). Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors.
  27. Dupras SK et al (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts.
  28. (2000). Electromechanical coupling between skeletal and cardiac muscle.
  29. (1998). Embryonic stem cell lines derived from human blastocysts.
  30. (2007). Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.
  31. (2010). Epicardium and myocardium originate from a common cardiogenic precursor pool. Trends Cardiovasc Med
  32. (2009). Epicardium and myocardium separate from a common precursor pool by crosstalk between bone morphogenetic protein- and fibroblast growth factor-signaling pathways.
  33. et al (2007) In vivo hepatocyte growth factor gene transfer reduces myocardial ischemia-reperfusion injury through its multiple actions.
  34. (2009). Evidence for cardiomyocyte renewal in humans.
  35. (2006). Fat tissue: an underappreciated source of stem cells for biotechnology.
  36. (2009). From fish to amphibians to mammals: in search of novel strategies to optimize cardiac regeneration.
  37. (2009). Geron gets green light for human trial of ES cellderived product.
  38. Guetta E et al (2002) Cellular cardiomyoplasty of cardiac fibroblasts by adenoviral delivery of MyoD ex vivo: an unlimited source of cells for myocardial repair. Circulation 106:I125–I130
  39. Han ZH et al (2010) Randomized controlled trials on the therapeutic effects of adult progenitor cells for myocardial infarction: meta-analysis. Expert Opin Biolog Ther 10:667–680
  40. Hassink R et al (2003) Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells.
  41. Holschermann H et al (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.
  42. Hornung CA et al (2007) Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis.
  43. Hosoda T et al (2010) Myocyte turnover in the aging human heart.
  44. (2008). Human cardiovascular progenitor cells develop from a KDR ? embryonic-stem-cell-derived population.
  45. (2010). Human embryonic stem cells: derivation, culture, and differentiation: a review.
  46. (2011). Identification and characterization of adenovirus early region 1bassociated protein 5 as a surface marker on undifferentiated human embryonic stem cells. Stem Cells Dev.
  47. (2006). Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial.
  48. (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.
  49. (2006). Induction of pluripotent stem cells form mouse embryonic and adult fibroblast cultures by defined factors.
  50. (2009). Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial.
  51. (2006). Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.
  52. (2007). Intramyocardial transplantation of autologous CD34? stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial.
  53. Katus HA et al (2008) BMP-2 and FGF-2 synergistically facilitate adoption of a cardiac phenotype in somatic bone marrow c-kit?/ Sca-1? stem cells.
  54. Kiessling F et al (2008) Sustained persistence of transplanted proangiogenic cells contributes to neovascularization and cardiac function after ischemia.
  55. (2009). Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study.
  56. Masino A et al (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response.
  57. Me ´rot J et al (2009) Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias.
  58. (2010). Mesoangioblasts from ventricular vessels can differentiate in vitro into cardiac myocytes with sinoatriallike properties.
  59. Metzele R et al (2010) Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction.
  60. (1980). Mitotic polyploidization of mouse heart myocytes during the first postnatal week.
  61. Muiznieks I et al (2009) Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow,adiposetissue,heartanddermis.StemCellRevRep5:378–386
  62. (2001). Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228 732 Med Biol Eng Comput
  63. (1991). Myocardial changes in pressure overload-induced left ventricular hypertrophy. A study on tissue composition, polyploidization and multinucleation.
  64. (2010). Myocardial regeneration potential of adipose tissue-derived stem cells.
  65. (1998). Myocyte proliferation in end-stage cardiac failure in humans.
  66. (2010). Nuclear reprogramming to a pluripotent state by three approaches.
  67. (2010). Origin of cardiac progenitor cells in the developing and postnatal heart.
  68. Ozono R et al (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines.
  69. Perez A,GarciaVerdugo JM et al (2004) Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94:223–229
  70. (2010). Phenotypes of stem cells from diverse origin. Cytom A 77A:6–10
  71. (2010). Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues.
  72. (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.
  73. (2002). Preimplantation human embryos and embryonic stem cells show comparable expression of stagespecific embryonic antigens.
  74. (1998). Primate embryonic stem cells.
  75. (2000). Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
  76. Ratajczak MZ et al (2011) Very small embryonic-like stem cells in cardiovascular repair.
  77. (2007). Role of bone morphogenetic proteins in cardiac differentiation.
  78. (2008). Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis.
  79. (2008). Skeletal myoblast transplantation: no MAGIC bullet for ischemic cardiomyopathy.
  80. (1983). Stage-specific embryonic antigens (SSEA-3 and -4) are epitopes of a unique globo-series ganglioside isolated from human teratocarcinoma cells.
  81. (2002). Surface antigens of human embryonic stem cells: changes upon differentiation in culture.
  82. (2009). Terzic A
  83. (2008). TGF-[beta] induces the differentiation of bone marrow stem cells into immature cardiomyocytes.
  84. (2010). The binding specificity of the marker antibodies Tra-1–60 and Tra-1–81 reveals a novel pluripotency associated type 1 lactosamine epitope. Glycobiology.
  85. (2007). The TRA-1-60 and TRA-1-81 human pluripotent stem cell markers are expressed on podocalyxin in embryonal carcinoma.
  86. (1984). Three monoclonal antibodies defining distinct differentiation antigens associated with different high molecular weight polypeptides on the surface of human embryonal carcinoma cells.
  87. Tomoda K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors.
  88. Trakhtenbrot L et al (2009) Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.
  89. (2011). Transient regenerative potential of the neonatal mouse heart.
  90. (2004). Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.
  91. (2007). Ventricular arrhythmias following intracoronary bone marrow stem cell transplantation.