Current Cardiovascular Imaging Reports

, Volume 2, Issue 1, pp 50–58

Comparison of adult versus embryonic stem cell therapy for cardiovascular disease: Insights from molecular imaging studies

Article

Abstract

In the previous decade, cardiac cell replacement therapy has emphasized adult stem cells such as skeletal myoblasts, bone marrow mononuclear cells, and endothelial progenitor cells. Functional restoration of systolic function has been documented in most of these cases, but beneficial results have rarely persisted for significant lengths of time due to failure of cells to survive and the as yet controversial role of transdifferentiation into endogenous tissue. Future efforts at cell replacement therapy will likely focus upon cellular derivatives of embryonic stem (ES) cells, which can be induced to form any cell type of the body. Use of ES cells, however, presents several novel considerations such as teratoma formation and immune rejection. This review summarizes the current progress made in the field of cardiac cell replacement therapy and the role noninvasive imaging can play in realizing the therapeutic potential of stem cells.

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References and Recommended Reading

  1. 1.
    Rosamond W, Flegal K, Furie K, et al.: Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008, 117:e25–e146.PubMedCrossRefGoogle Scholar
  2. 2.
    Rosenzweig A: Cardiac cell therapy—mixed results from mixed cells. N Engl J Med 2006, 355:1274–1277.PubMedCrossRefGoogle Scholar
  3. 3.
    Chiu RC, Zibaitis A, Kao RL: Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg 1995, 60:12–18.PubMedGoogle Scholar
  4. 4.
    Taylor DA, Atkins BZ, Hungspreugs P, et al.: Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 1998, 4:929–933.PubMedCrossRefGoogle Scholar
  5. 5.
    Leobon B, Garcin I, Menasche P, et al.: Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci U S A 2003, 100:7808–7811.PubMedCrossRefGoogle Scholar
  6. 6.
    Hagege AA, Carrion C, Menasche P, et al.: Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Lancet 2003, 361:491–492.PubMedCrossRefGoogle Scholar
  7. 7.
    Tomita S, Li RK, Weisel RD, et al.: Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 1999, 100(Suppl 19):II247–II256.PubMedGoogle Scholar
  8. 8.
    Orlic D, Kajstura J, Chimenti S, et al.: Bone marrow cells regenerate infarcted myocardium. Nature 2001, 410:701–705.PubMedCrossRefGoogle Scholar
  9. 9.
    Jackson KA, Majka SM, Wang H, et al.: Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001, 107:1395–1402.PubMedCrossRefGoogle Scholar
  10. 10.
    Murry CE, Soonpaa MH, Reinecke H, et al.: Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004, 428:664–668.PubMedCrossRefGoogle Scholar
  11. 11.
    Balsam LB, Wagers AJ, Christensen JL, et al.: Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004, 428:668–673.PubMedCrossRefGoogle Scholar
  12. 12.
    Kamihata H, Matsubara H, Nishiue T, et al.: Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 2001, 104:1046–1052.PubMedCrossRefGoogle Scholar
  13. 13.
    Kalka C, Masuda H, Takahashi T, et al.: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 2000, 97:3422–3427.PubMedCrossRefGoogle Scholar
  14. 14.
    Takamiya M, Okigaki M, Jin D, et al.: Granulocyte colony-stimulating factor-mobilized circulating c-Kit+/Flk-1+ progenitor cells regenerate endothelium and inhibit neointimal hyperplasia after vascular injury. Arterioscler Thromb Vasc Biol 2006, 26:751–757.PubMedCrossRefGoogle Scholar
  15. 15.
    Asahara T, Murohara T, Sullivan A, et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997, 275:964–967.PubMedCrossRefGoogle Scholar
  16. 16.
    Takahashi T, Kalka C, Masuda H, et al.: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999, 5:434–438.PubMedCrossRefGoogle Scholar
  17. 17.
    Kocher AA, Schuster MD, Szabolcs MJ, et al.: Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001, 7:430–436.PubMedCrossRefGoogle Scholar
  18. 18.
    Pittenger MF, Martin BJ: Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004, 95:9–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Pittenger MF, Mackay AM, Beck SC, et al.: Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284:143–147.PubMedCrossRefGoogle Scholar
  20. 20.
    Jiang Y, Jahagirdar BN, Reinhardt RL, et al.: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002, 418:41–49.PubMedCrossRefGoogle Scholar
  21. 21.
    Tse WT, Pendleton JD, Beyer WM, et al.: Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003, 75:389–397.PubMedCrossRefGoogle Scholar
  22. 22.
    Le Blanc K, Frassoni F, Ball L, et al.: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008, 371:1579–1586.PubMedCrossRefGoogle Scholar
  23. 23.
    Barbash IM, Chouraqui P, Baron J, et al.: Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003, 108:863–868.PubMedCrossRefGoogle Scholar
  24. 24.
    Vulliet PR, Greeley M, Halloran SM, et al.: Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 2004, 363:783–784.PubMedCrossRefGoogle Scholar
  25. 25.
    Swijnenburg RJ, Schrepfer S, Govaert JA, et al.: Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc Natl Acad Sci U S A 2008, 105:12991–12996.PubMedCrossRefGoogle Scholar
  26. 26.
    Swijnenburg RJ, Schrepfer S, Cao F, et al.: In vivo imaging of embryonic stem cells reveals patterns of survival and rejection following transplantation. Stem Cells Dev 2008, 17:1023–1030.PubMedCrossRefGoogle Scholar
  27. 27.
    Maitra A, Arking DE, Shivapurkar N, et al.: Genomic alterations in cultured human embryonic stem cells. Nat Genet 2005, 37:1099–1103.PubMedCrossRefGoogle Scholar
  28. 28.
    Xu C, Police S, Rao N, et al.: Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 2002, 91:501–508.PubMedCrossRefGoogle Scholar
  29. 29.
    Kolossov E, Bostani T, Roell W, et al.: Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. J Exp Med 2006, 203:2315–2327.PubMedCrossRefGoogle Scholar
  30. 30.
    Cao F, Wagner RA, Wilson KD, et al.: Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS ONE 2008, 3:e3474.PubMedCrossRefGoogle Scholar
  31. 31.
    He JQ, Ma Y, Lee Y, et al.: Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 2003, 93:32–39.PubMedCrossRefGoogle Scholar
  32. 32.
    Xue T, Cho HC, Akar FG, et al.: Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 2005, 111:11–20.PubMedCrossRefGoogle Scholar
  33. 33.
    van Laake LW, Passier R, Doevendans PA, et al.: Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res 2008, 102:1008–1010.PubMedCrossRefGoogle Scholar
  34. 34.
    Laflamme MA, Chen KY, Naumova AV, et al.: Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 2007, 25:1015–1024.PubMedCrossRefGoogle Scholar
  35. 35.
    Li Z, Wu JC, Sheikh AY, et al.: Differentiation, survival, and function of embryonic stem cell derived endothelial cells for ischemic heart disease. Circulation 2007, 116(Suppl 11):I46–I54.PubMedGoogle Scholar
  36. 36.
    Wang ZZ, Au P, Chen T, et al.: Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol 2007, 25:317–318.PubMedCrossRefGoogle Scholar
  37. 37.
    Meyer GP, Wollert KC, Lotz J, et al.: 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 2006, 113:1287–1294.PubMedCrossRefGoogle Scholar
  38. 38.
    Assmus B, Honold J, Schachinger V, et al.: Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006, 355:1222–1232.PubMedCrossRefGoogle Scholar
  39. 39.
    Lunde K, Solheim S, Aakhus S, et al.: Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006, 355:1199–1209.PubMedCrossRefGoogle Scholar
  40. 40.
    Schachinger V, Erbs S, Elsasser A, et al.: Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006, 355:1210–1221.PubMedCrossRefGoogle Scholar
  41. 41.
    Menasche P, Alfieri O, Janssens S, et al.: The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 2008, 117:1189–1200.PubMedCrossRefGoogle Scholar
  42. 42.
    Kraitchman DL, Heldman AW, Atalar E, et al.: In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003, 107:2290–2293.PubMedCrossRefGoogle Scholar
  43. 43.
    Amado LC, Saliaris AP, Schuleri KH, et al.: Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 2005, 102:11474–11479.PubMedCrossRefGoogle Scholar
  44. 44.
    Hofmann M, Wollert KC, Meyer GP, et al.: Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005, 111:2198–2202.PubMedCrossRefGoogle Scholar
  45. 45.
    Li Z, Suzuki Y, Huang M, et al.: Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells 2008, 26:864–873.PubMedCrossRefGoogle Scholar
  46. 46.
    Cao F, Lin S, Xie X, et al.: In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation 2006, 113:1005–1014.PubMedCrossRefGoogle Scholar
  47. 47.
    van der Bogt KE, Sheikh AY, Schrepfer S, et al.: Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation 2008, 118(Suppl 14):S121–S129.PubMedCrossRefGoogle Scholar
  48. 48.
    Gyöngyösi M, Marian T, Trón L, et al.: Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging 2008, 1:94–103.CrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  1. 1.Stanford University School of MedicineStanfordUSA

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