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Cardiovascular surgery for realization of regenerative medicine

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Abstract

Regenerative medicine is emerging as a new approach to the treatment of severe cardiovascular diseases that are resistant to conventional therapies. Although the type of cell transplanted (e.g., pluripotent stem cells, bone marrow-derived stem cells, skeletal myoblasts, or cardiac stem cells) influences the outcome of stem cell transplantation, the method of transplantation is also important, as the efficiency of engraftment after simple needle injection is poor. Scaffold-free cell sheet transplantation technology is one of the most promising methods in this regard. Although the results of clinical trials of stem cell therapy have been marginal to date, further elucidation of the actual mechanisms of cardiac repair following cell therapy would enhance the potential for full-scale implementation of stem cell therapy. In addition to stem cell therapy, the field of cardiovascular regenerative medicine includes interspecific chimera technology, drug delivery systems using biodegradable materials, and gene therapy. Integration of these new modalities with conventional therapies will be important to realize the goal of cardiovascular regenerative medicine tailored to the condition of each individual patient. Cardiovascular surgery would be an excellent means of carrying out this strategy and could potentially resolve the health problems of the increasing number of advanced cardiovascular patients. Herein, we review the recent basic and clinical research associated with the realization of regenerative medicine in the field of cardiovascular surgery.

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References

  1. Sakata R, Fujii Y, Kuwano H. Thoracic and cardiovascular surgery in Japan during 2009: annual report by the Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg. 2011;59:636–67.

    Article  PubMed  Google Scholar 

  2. Joggerst SJ, Hatzopoulos AK. Stem cell therapy for cardiac repair: benefits and barriers. Expert Rev Mol Med. 2009;11:e20.

    Article  PubMed  Google Scholar 

  3. Ohno N, Fedak PW, Weisel RD, Komeda M, Mickle DA, Li RK. Cell transplantation in non-ischemic dilated cardiomyopathy: a novel biological approach for ventricular restoration. Jpn J Thorac Cardiovasc Surg. 2002;50:457–60.

    Article  PubMed  Google Scholar 

  4. Sakakibara Y, Tambara K, Lu F, Nishina T, Nagaya N, Nishimura K, et al. Combined procedure of surgical repair and cell transplantation for left ventricular aneurysm: an experimental study. Circulation. 2002;106:I193–7.

    PubMed  Google Scholar 

  5. Chien KR. Regenerative medicine and human models of human disease. Nature. 2008;453:302–5.

    Article  PubMed  CAS  Google Scholar 

  6. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  PubMed  CAS  Google Scholar 

  7. Murry CE, Keller G. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell. 2008;132:661–80.

    Article  PubMed  CAS  Google Scholar 

  8. Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, et al. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature. 2000;408:92–6.

    Article  PubMed  CAS  Google Scholar 

  9. Yamashita JK, Takano M, Hiraoka-Kanie M, Shimazu C, Yan P, Yanagi K, et al. Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction. FASEB J. 2005;19:1534–6.

    PubMed  CAS  Google Scholar 

  10. Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol. 2007;25:1015–24.

    Article  PubMed  CAS  Google Scholar 

  11. Sone M, Itoh H, Yamahara K, Yamashita JK, Yurugi-Kobayashi T, Nonoguchi A, et al. Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. Arterioscler Thromb Vasc Biol. 2007;27:2127–34.

    Article  PubMed  CAS  Google Scholar 

  12. Masumoto H, Matsuo T, Yamamizu K, Uosaki H, Narazaki G, Katayama S, et al. Pluripotent stem cell-engineered cell sheets re-assembled with defined cardiovascular populations ameliorate reduction in infarct heart function through cardiomyocyte-mediated neovascularization. Stem Cells. 2012;30:1196–205.

    Article  PubMed  CAS  Google Scholar 

  13. van Laake LW, Passier R, Monshouwer-Kloots J, Verkleij AJ, Lips DJ, Freund C, et al. Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. Stem Cell Res. 2007;1:9–24.

    Article  PubMed  Google Scholar 

  14. Blum B, Benvenisty N. The tumorigenicity of human embryonic stem cells. Adv Cancer Res. 2008;100:133–58.

    Article  PubMed  Google Scholar 

  15. Draper JS, Pigott C, Thomson JA, Andrews PW. Surface antigens of human embryonic stem cells: changes upon differentiation in culture. J Anat. 2002;200:249–58.

    Article  PubMed  CAS  Google Scholar 

  16. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  PubMed  CAS  Google Scholar 

  17. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  PubMed  CAS  Google Scholar 

  18. Narazaki G, Uosaki H, Teranishi M, Okita K, Kim B, Matsuoka S, et al. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation. 2008;118:498–506.

    Article  PubMed  Google Scholar 

  19. Uosaki H, Fukushima H, Takeuchi A, Matsuoka S, Nakatsuji N, Yamanaka S, et al. Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS One. 2011;6:e23657.

    Article  PubMed  CAS  Google Scholar 

  20. Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8:409–12.

    Article  PubMed  CAS  Google Scholar 

  21. Hiratsuka M, Uno N, Ueda K, Kurosaki H, Imaoka N, Kazuki K, et al. Integration-free iPS cells engineered using human artificial chromosome vectors. PLoS One. 2011;6:e25961.

    Article  PubMed  CAS  Google Scholar 

  22. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–5.

    Article  PubMed  CAS  Google Scholar 

  23. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001;98:10344–9.

    Article  PubMed  CAS  Google Scholar 

  24. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664–8.

    Article  PubMed  CAS  Google Scholar 

  25. Leistner DM, Fischer-Rasokat U, Honold J, Seeger FH, Schächinger V, Lehmann R, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy. Clin Res Cardiol. 2011;100:925–34.

    Article  PubMed  Google Scholar 

  26. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, 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;113:1287–94.

    Article  PubMed  Google Scholar 

  27. Assmus B, Rolf A, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, et al. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail. 2010;3:89–96.

    Article  PubMed  Google Scholar 

  28. Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, et al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA. 2011;306:2110–9.

    Article  PubMed  CAS  Google Scholar 

  29. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–9.

    Article  PubMed  CAS  Google Scholar 

  30. Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, Sakai T, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation. 1999;100:II247–56.

    Google Scholar 

  31. Dai W, Hale SL, Martin BJ, Kuang JQ, Dow JS, Wold LE, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation. 2005;112:214–23.

    Article  PubMed  Google Scholar 

  32. Le Blanc K, Ringdén O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007;262:509–25.

    Article  PubMed  Google Scholar 

  33. Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med. 2006;12:459–65.

    Article  PubMed  CAS  Google Scholar 

  34. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94:92–5.

    Article  PubMed  Google Scholar 

  35. Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW. Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation. 2004;109:3154–7.

    Article  PubMed  Google Scholar 

  36. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.

    Article  PubMed  CAS  Google Scholar 

  37. Hristov M, Weber C. Endothelial progenitor cells in vascular repair and remodeling. Pharmacol Res. 2008;58:148–51.

    Article  PubMed  CAS  Google Scholar 

  38. Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res. 2001;88:167–74.

    Article  PubMed  CAS  Google Scholar 

  39. Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation. 2001;103:2776–9.

    Article  PubMed  CAS  Google Scholar 

  40. Patenaude A, Parker J, Karsan A. Involvement of endothelial progenitor cells in tumor vascularization. Microvasc Res. 2010;79:217–23.

    Article  PubMed  CAS  Google Scholar 

  41. Kalka C, Tehrani H, Laudenberg B, Vale PR, Isner JM, Asahara T, et al. VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease. Ann Thorac Surg. 2000;70:829–34.

    Article  PubMed  CAS  Google Scholar 

  42. Fukuhara S, Tomita S, Nakatani T, Ohtsu Y, Ishida M, Yutani C, et al. G-CSF promotes bone marrow cells to migrate into infarcted mice heart, and differentiate into cardiomyocytes. Cell Transplant. 2004;13:741–8.

    Article  PubMed  Google Scholar 

  43. Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest. 2001;108:399–405.

    PubMed  CAS  Google Scholar 

  44. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7:430–6.

    Article  PubMed  CAS  Google Scholar 

  45. Tendera M, Wojakowski W, Ruzyłło W, Chojnowska L, Kepka C, Tracz W, et al. Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J. 2009;30:1313–21.

    Article  PubMed  Google Scholar 

  46. den Dekker WK, Houtgraaf JH, Onuma Y, Benit E, de Winter RJ, Wijns W, et al. Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients. Atherosclerosis. 2011;219:245–52.

    Article  Google Scholar 

  47. Miglionico M, Patti G, D’Ambrosio A, Di Sciascio G. Percutaneous coronary intervention utilizing a new endothelial progenitor cells antibody-coated stent: a prospective single-center registry in high-risk patients. Catheter Cardiovasc Interv. 2008;71:600–4.

    Article  PubMed  Google Scholar 

  48. Jujo K, Ii M, Losordo DW. Endothelial progenitor cells in neovascularization of infarcted myocardium. J Mol Cell Cardiol. 2008;45:530–44.

    Article  PubMed  CAS  Google Scholar 

  49. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89:E1–7.

    Article  PubMed  CAS  Google Scholar 

  50. Buckingham M, Montarras D. Skeletal muscle stem cells. Curr Opin Genet Dev. 2008;18:330–6.

    Article  PubMed  CAS  Google Scholar 

  51. Murry CE, Wiseman RW, Schwartz SM, Hauschka SD. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest. 1996;98:2512–23.

    Article  PubMed  CAS  Google Scholar 

  52. Pagani FD, DerSimonian H, Zawadzka A, Wetzel K, Edge AS, Jacoby DB, et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol. 2003;41:879–88.

    Article  PubMed  Google Scholar 

  53. Arsic N, Mamaeva D, Lamb NJ, Fernandez A. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages. Exp Cell Res. 2008;314:1266–80.

    Article  PubMed  CAS  Google Scholar 

  54. Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998;4:929–33.

    Article  PubMed  CAS  Google Scholar 

  55. Farahmand P, Lai TY, Weisel RD, Fazel S, Yau T, Menasché P, et al. Skeletal myoblasts preserve remote matrix architecture and global function when implanted early or late after coronary ligation into infarcted or remote myocardium. Circulation. 2008;118:S130–7.

    Article  PubMed  Google Scholar 

  56. Siminiak T, Fiszer D, Jerzykowska O, Grygielska B, Rozwadowska N, Kałmucki P, et al. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. Eur Heart J. 2005;26:1188–95.

    Article  PubMed  Google Scholar 

  57. Dib N, Dinsmore J, Lababidi Z, White B, Moravec S, Campbell A, et al. One-year follow-up of feasibility and safety of the first US, randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic cardiomyopathy (CAuSMIC study). JACC Cardiovasc Interv. 2009;2:9–16.

    Google Scholar 

  58. Menasché P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117:1189–200.

    Article  PubMed  Google Scholar 

  59. Roell W, Lewalter T, Sasse P, Tallini YN, Choi BR, Breitbach M, et al. Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature. 2007;450:819–24.

    Article  PubMed  CAS  Google Scholar 

  60. Suzuki K, Murtuza B, Beauchamp JR, Smolenski RT, Varela-Carver A, Fukushima S, et al. Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart. FASEB J. 2004;18:1153–5.

    PubMed  CAS  Google Scholar 

  61. Development of New Strategy for Severe Heart Failure Using Autologous Myoblast Sheets. UMIN Clinical Trials Registry (UMIN-CTR). http://www.umin.ac.jp/ctr/index-j.htm UMIN000003273 (Accessed 8 April 2012).

  62. Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Capasso JM. Hypertensive cardiomyopathy. Myocyte nuclei hyperplasia in the mammalian rat heart. J Clin Invest. 1990;85:994–7.

    Article  PubMed  CAS  Google Scholar 

  63. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med. 2001;344:1750–7.

    Article  PubMed  CAS  Google Scholar 

  64. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324:98–102.

    Article  PubMed  CAS  Google Scholar 

  65. Ellison GM, Torella D, Karakikes I, Nadal-Ginard B. Myocyte death and renewal: modern concepts of cardiac cellular homeostasis. Nat Clin Pract Cardiovasc Med. 2007;4:S52–9.

    Article  PubMed  CAS  Google Scholar 

  66. Challen GA, Little MH. A side order of stem cells: the SP phenotype. Stem Cells. 2006;24:3–12.

    Article  PubMed  Google Scholar 

  67. Oyama T, Nagai T, Wada H, Naito AT, Matsuura K, Iwanaga K, et al. Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. J Cell Biol. 2007;176:329–41.

    Article  PubMed  CAS  Google Scholar 

  68. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76.

    Article  PubMed  CAS  Google Scholar 

  69. Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA. 2003;100:12313–8.

    Article  PubMed  CAS  Google Scholar 

  70. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95:911–21.

    Article  PubMed  CAS  Google Scholar 

  71. Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, et al. Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. J Am Coll Cardiol. 2008;52:1858–65.

    Article  PubMed  CAS  Google Scholar 

  72. Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;311:1880–5.

    Article  PubMed  CAS  Google Scholar 

  73. Smart N, Bollini S, Dubé KN, Vieira JM, Zhou B, Davidson S, et al. De novo cardiomyocytes from within the activated adult heart after injury. Nature. 2011;474:640–4.

    Article  PubMed  CAS  Google Scholar 

  74. Torella D, Ellison GM, Méndez-Ferrer S, Ibanez B, Nadal-Ginard B. Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med. 2006;3:S8–13.

    Article  PubMed  CAS  Google Scholar 

  75. Siu CW, Tse HF. Cardiac regeneration: messages from CADUCEUS. Lancet. 2012;379:870–1.

    Article  PubMed  Google Scholar 

  76. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379:895–904.

    Article  PubMed  Google Scholar 

  77. Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378:1847–57.

    Article  PubMed  Google Scholar 

  78. AutoLogous human CArdiac-Derived stem cell to treat Ischemic cArdiomyopathy (ALCADIA) trial. http://www.clinicaltrials.gov/ct2/show/ NCT00981006 (Accessed 8 April 2012).

  79. Pelacho B, Mazo M, Gavira JJ, Prósper F. Adult stem cells: from new cell sources to changes in methodology. J Cardiovasc Transl Res. 2011;4:154–60.

    Article  PubMed  Google Scholar 

  80. Müller-Ehmsen J, Whittaker P, Kloner RA, Dow JS, Sakoda T, Long TI, et al. Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. J Mol Cell Cardiol. 2002;34:107–16.

    Article  PubMed  Google Scholar 

  81. Teng CJ, Luo J, Chiu RC, Shum-Tim D. Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: implications for cellular cardiomyoplasty. J Thorac Cardiovasc Surg. 2006;132:628–32.

    Article  PubMed  Google Scholar 

  82. Cortes-Morichetti M, Frati G, Schussler O, Duong Van Huyen JP, Lauret E, Genovese JA. Association between a cell-seeded collagen matrix and cellular cardiomyoplasty for myocardial support and regeneration. Tissue Eng. 2007;13:2681–7.

    Article  PubMed  CAS  Google Scholar 

  83. Christman KL, Lee RJ. Biomaterials for the treatment of myocardial infarction. J Am Coll Cardiol. 2006;48:907–13.

    Article  PubMed  CAS  Google Scholar 

  84. Simpson D, Liu H, Fan TH, Nerem R, Dudley SC Jr. A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling. Stem Cells. 2007;25:2350–7.

    Article  PubMed  Google Scholar 

  85. Zimmermann WH, Melnychenko I, Wasmeier G, Didié M, Naito H, Nixdorff U, et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med. 2006;12:452–8.

    Article  PubMed  CAS  Google Scholar 

  86. Okano T, Yamada N, Sakai H, Sakurai Y. A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly (N-isopropylacrylamide). J Biomed Mater Res. 1993;27:1243–51.

    Article  PubMed  CAS  Google Scholar 

  87. Bartosh TJ, Wang Z, Rosales AA, Dimitrijevich SD, Roque RS. 3D-model of adult cardiac stem cells promotes cardiac differentiation and resistance to oxidative stress. J Cell Biochem. 2008;105:612–23.

    Article  PubMed  CAS  Google Scholar 

  88. Wei HJ, Chen CH, Lee WY, Chiu I, Hwang SM, Lin WW, et al. Bioengineered cardiac patch constructed from multilayered mesenchymal stem cells for myocardial repair. Biomaterials. 2008;29:3547–56.

    Article  PubMed  CAS  Google Scholar 

  89. Shudo Y, Miyagawa S, Fukushima S, Saito A, Shimizu T, Okano T, et al. Novel regenerative therapy using cell-sheet covered with omentum flap delivers a huge number of cells in a porcine myocardial infarction model. J Thorac Cardiovasc Surg. 2011;142:1188–96.

    Article  PubMed  Google Scholar 

  90. Mazo M, Pelacho B, Prósper F. Stem cell therapy for chronic myocardial infarction. J Cardiovasc Transl Res. 2010;3:79–88.

    Article  PubMed  Google Scholar 

  91. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21.

    Article  PubMed  CAS  Google Scholar 

  92. Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y, Ibata M, et al. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell. 2010;142:787–99.

    Article  PubMed  CAS  Google Scholar 

  93. Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency (JST). http://www.jst.go.jp/erato/project/nks_P/nks_P.html.

  94. Tabata Y. Tissue regeneration based on growth factor release. Tissue Eng. 2003;9:S5–15.

    Article  PubMed  CAS  Google Scholar 

  95. Marui A, Tabata Y, Kojima S, Yamamoto M, Tambara K, Nishina T, et al. A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel: an initial report of the phase I–IIa study. Circ J. 2007;71:1181–6.

    Article  PubMed  CAS  Google Scholar 

  96. Gaffney MM, Hynes SO, Barry F, O’Brien T. Cardiovascular gene therapy: current status and therapeutic potential. Br J Pharmacol. 2007;152:175–88.

    Article  PubMed  CAS  Google Scholar 

  97. Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation. 2011;124:304–13.

    Article  PubMed  CAS  Google Scholar 

  98. Frost RJ, van Rooij E. miRNAs as therapeutic targets in ischemic heart disease. J Cardiovasc Transl Res. 2010;3:280–9.

    Article  PubMed  Google Scholar 

  99. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010;142:375–86.

    Article  PubMed  CAS  Google Scholar 

  100. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485:593–8.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ryuzo Sakata.

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The review was submitted at the invitation of the editorial committee.

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Masumoto, H., Sakata, R. Cardiovascular surgery for realization of regenerative medicine. Gen Thorac Cardiovasc Surg 60, 744–755 (2012). https://doi.org/10.1007/s11748-012-0139-7

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