Regenerative Chimerism Bioengineered Through Stem Cell Reprogramming

  • Timothy J. Nelson
  • Almudena Martinez-Fernandez
  • Satsuki Yamada
  • Andre Terzic
Chapter

Abstract

Regenerative medicine aims to restore damaged tissues in order to reverse disease progression and provide a sustainable solution that cures the root cause of the disease process. Although natural mechanisms of repair are ubiquitous, disruption of the homeostatic balance affects the equilibrium between health and disease due to insufficient tissue renewal in chronic degenerative conditions. Augmentation of the diseased tissue repair capacity through chimerism offers a strategy that spans all fields of medicine and surgery from natural chimerism for tissue rejuvenation, to surgical chimerism for organ replacement, to bioengineered chimerism for targeted regeneration. Technological breakthroughs in nuclear reprogramming now provide a platform to advance a broad range of solutions for regenerative medicine built on the foundation of pluripotent autologous stem cells. By optimizing the safety and effectiveness for stem cell production and ensuring tissue-specific differentiation of progenitors, induced pluripotent stem cells (iPS) offer an unprecedented opportunity to accelerate personalized applications with cell-based products to bioengineer health from disease.

Keywords

Stem Cell Embryonic Stem Cell Pluripotent Stem Cell Regenerative Medicine Somatic Cell Nuclear Transfer 
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.

References

  1. Aoi T, Yae K, Nakagawa M et al (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321:699–702.PubMedGoogle Scholar
  2. Aasen T, Raya A, Barrero MJ et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26:1276–1284.PubMedGoogle Scholar
  3. 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 167:989–997.PubMedGoogle Scholar
  4. Atala A (2008) Advances in tissue and organ replacement. Curr Stem Cell Res Ther 3:21–31.PubMedGoogle Scholar
  5. Anversa P, Nadal-Ginard B (2002) Myocyte renewal and ventricular remodelling. Nature 415:240–243.PubMedGoogle Scholar
  6. Anversa P, Kajstura J, Leri A et al (2006) Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation 113:1451–1463.PubMedGoogle Scholar
  7. Banito A, Rashid ST, Acosta JC et al (2009) Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23:2134–2139.PubMedGoogle Scholar
  8. Barnard CN (1967) A human cardiac transplant: an interim report of a successful operation ­performed at Groote Schuur Hospital, Capetown. S Afr Med J 41:1271.PubMedGoogle Scholar
  9. Bartunek J, Vanderheyden M, Wijns W et al (2007) Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny? Nat Clin Pract Cardiovasc Med 4 (Suppl 1):S100–105.PubMedGoogle Scholar
  10. Behfar A, Faustino RS, Arrell DK et al (2008) Guided stem cell cardiopoiesis: discovery and translation. J Mol Cell Cardiol 45:523–529.PubMedGoogle Scholar
  11. Bergmann O, Bhardwaj RD, Bernard S et al (2009). Evidence for cardiomyocyte renewal in humans. Science 324:98–102.PubMedGoogle Scholar
  12. Beyhan Z, Iager AE, Cibelli JB (2007) Interspecies nuclear transfer: Implications for embryonic stem cell biology. Cell Stem Cell 1:502–512.PubMedGoogle Scholar
  13. Boland MJ, Hazen JL, Nazor KL, et al (2009) Adult mice generated from induced pluripotent stem cells. Nature 461:91–94.PubMedGoogle Scholar
  14. Byrne JA, Pedersen DA, Clepper LL et al (2007) Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature 450:497–502.PubMedGoogle Scholar
  15. Carmeliet P, Ferreira V, Breier G et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439.PubMedGoogle Scholar
  16. Carrel A, Guthrie CC (1905) The transplantation of veins and organs. J Am Med Assoc 10:1101.Google Scholar
  17. Cortese DA (2007) A vision of individualized medicine in the context of global health. Clin Pharmacol Ther 82:491–493.PubMedGoogle Scholar
  18. Daley GQ, Scadden DT (2008) Prospects for stem cell-based therapy. Cell 132:544–548.PubMedGoogle Scholar
  19. Deb A, Wang S, Skelding KA et al (2003) Bone marrow-derived cardiomyocytes are present in adult human heart: A study of gender-mismatched bone marrow transplantation patients. Circulation 107:1247–1249.PubMedGoogle Scholar
  20. Deng J, Shoemaker R, Xie B et al (2009) Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol 27:353–360.PubMedGoogle Scholar
  21. Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115:572–583.PubMedGoogle Scholar
  22. Dimos JT, Rodolfa KT, Niakan KK et al (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218–1221.PubMedGoogle Scholar
  23. Drexler H, Meyer GP, Wollert KC (2006) Bone-marrow-derived cell transfer after ST-elevation myocardial infarction: lessons from the BOOST trial. Nat Clin Pract Cardiovasc Med 3 (Suppl 1):S65–68.PubMedGoogle Scholar
  24. Eminli S, Utikal J, Arnold K et al (2008) Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells 26:2467–2474.PubMedGoogle Scholar
  25. Feng B, Jiang J, Kraus P et al (2009) Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11:197–203.PubMedGoogle Scholar
  26. Foley AC, Gupta RW, Guzzo RM et al (2006) Embryonic heart induction. Ann NY Acad Sci 1080:85–96.PubMedGoogle Scholar
  27. Fraidenraich D, Stillwell E, Romero E et al (2004) Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells. Science 306:247–252.PubMedGoogle Scholar
  28. French AJ, Adams CA, Anderson LS et al (2008) Development of human cloned blastocysts ­following somatic cell nuclear transfer with adult fibroblasts. Stem Cells 26:485–493.PubMedGoogle Scholar
  29. Goldstein DJ, Oz MC, Rose EA (1998) Implantable left ventricular assist devices. N Engl J Med 339:1522–1533.PubMedGoogle Scholar
  30. Hagège AA, Marolleau JP, Vilquin JT et al (2006) Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation 114(1 Suppl):I108–113.PubMedGoogle Scholar
  31. Hall VJ, Stojkovic M (2006) The status of human nuclear transfer. Stem Cell Rev 2:301–308.PubMedGoogle Scholar
  32. Hanna J, Wernig M, Markoulaki S et al (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318:1920–1923.PubMedGoogle Scholar
  33. Hanna J, Markoulaki S, Schorderet P et al (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133:250–264.PubMedGoogle Scholar
  34. Hardy JD, Chavez CM, Kurrus FD et al (1964) Heart transplantation in man. J Am Med Assoc 188:114.Google Scholar
  35. Hirashima M, Lu Y, Byers L et al (2003) Trophoblast expression of fms-like tyrosine kinase 1 is not required for the establishment of the maternal-fetal interface in the mouse placenta. Proc Natl Acad Sci USA 100:15637–15642.PubMedGoogle Scholar
  36. Hong H, Takahashi K, Ichisaka T et al (2009) Suppression of induced pluripotent stem cell ­generation by the p53-p21 pathway. Nature 460:1132–1135.PubMedGoogle Scholar
  37. 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 13:970–974.PubMedGoogle Scholar
  38. Huangfu D, Osafune K, Maehr R et al (2008) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26:1269–1275.PubMedGoogle Scholar
  39. Hunt SA, Abraham WT, Chin MH et al (2009) 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 119:e391–479.PubMedGoogle Scholar
  40. Jaenisch R, Young R (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132:567–582.PubMedGoogle Scholar
  41. Jahangir A, Sagar S, Terzic A (2007) Aging and cardioprotection. J Appl Physiol 103:2120–2128.PubMedGoogle Scholar
  42. 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 367:113–121.PubMedGoogle Scholar
  43. Kaji K, Norrby K, Paca A et al (2009) Virus-free induction of pluripotency and subsequent ­excision of reprogramming factors. Nature 458:771–775.PubMedGoogle Scholar
  44. Kajstura J, Hosoda T, Bearzi C et al (2008a) The human heart: A self-renewing organ. Clin Transl Sci 1:80–86.PubMedGoogle Scholar
  45. Kajstura J, Urbanek K, Rota M et al (2008b) Cardiac stem cells and myocardial disease. J Mol Cell Cardiol 45:505–513.PubMedGoogle Scholar
  46. Kattman SJ, Huber TL, Keller GM (2006) Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell 11:723–732.PubMedGoogle Scholar
  47. Kawamura T, Suzuki J, Wang YV et al (2009) Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460:1140–1144.PubMedGoogle Scholar
  48. Kim JB, Zaehres H, Wu G et al (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454:646–650.PubMedGoogle Scholar
  49. Kim D, Kim CH, Moon J et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 6:472–476.Google Scholar
  50. Kørbling M, Estrov Z (2003) Adult stem cells for tissue repair - a new therapeutic concept? N Engl J Med 349:570–582.PubMedGoogle Scholar
  51. Kubo H, Jaleel N, Kumarapeli A et al (2008) Increased cardiac myocyte progenitors in failing human hearts. Circulation 118:649–657.PubMedGoogle Scholar
  52. Laird DJ, von Andrian UH, Wagers AJ (2008) Stem cell trafficking in tissue development, growth, and disease. Cell 132:612–630.PubMedGoogle Scholar
  53. Leri A, Kajstura J, Anversa P et al (2008) Myocardial regeneration and stem cell repair. Curr Probl Cardiol. 33:91–153.PubMedGoogle Scholar
  54. Li H, Collado M, Villasante A et al (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460:1136–1139.PubMedGoogle Scholar
  55. Li JY, Christophersen NS, Hall V et al (2008) Critical issues of clinical human embryonic stem cell therapy for brain repair. Trends Neurosci 31:146–153.PubMedGoogle Scholar
  56. Loh Y, Agarwal S, Park I et al (2009) Generation of induced pluripotent stem cells from human blood. Blood 113:5476–5479.PubMedGoogle Scholar
  57. Lough J, Sugi Y (2000) Endoderm and heart development. Dev Dyn. 217:327–342.PubMedGoogle Scholar
  58. Lower RR, Shumway NE (1960) Studies on the orthotopic homotransplantation of the canine heart. Surg Forum 11:18.PubMedGoogle Scholar
  59. Lunde K, Solheim S, Aakhus S (2007) Exercise capacity and quality of life after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: results from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) randomized controlled trial. Am Heart J 154:710.e1–8.PubMedGoogle Scholar
  60. Maherali N, Sridharan R, Xie W et al (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55–70.PubMedGoogle Scholar
  61. Marion RM, Strati K, Li H et al (2009a) A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460:1149–1153.PubMedGoogle Scholar
  62. Marion RM, Strati K, Li H et al (2009b) Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4:141–154.PubMedGoogle Scholar
  63. Meissner A, Wernig M, Jaenisch R (2007) Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol 25:1177–1181.PubMedGoogle Scholar
  64. Menasché P, Hagège AA, Scorsin M et al (2001) Myoblast transplantation for heart failure. Lancet 357:279–280.PubMedGoogle Scholar
  65. Mauritz C, Schwanke K, Reppel M et al (2008) Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation 118: 507–517.PubMedGoogle Scholar
  66. Maehr R, Chen S, Snitow M et al (2009) Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA 106:15768–15773.PubMedGoogle Scholar
  67. Martinez-Fernandez A, Nelson TJ, Yamada S et al (2009) iPS Programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circ Res 105:648–656.PubMedGoogle Scholar
  68. Menasché 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. 117:1189–1200.PubMedGoogle Scholar
  69. Mikkelsen TS, Hanna J, Zhang X et al (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454:49–55.PubMedGoogle Scholar
  70. Moretti A, Caron L, Nakano A et al (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127:1151–1165.PubMedGoogle Scholar
  71. Nagy A, Rossant J, Nagy R et al (1993) Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci USA 90:8424–8428.PubMedGoogle Scholar
  72. Nakagawa M, Koyanagi M, Tanabe K et al (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106.PubMedGoogle Scholar
  73. Narazaki G, Uosaki H, Teranishi M et al (2008) Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation 118:498–506.PubMedGoogle Scholar
  74. Nelson TJ, Behfar A, Terzic A (2008a) Strategies for therapeutic repair: The “R3” regenerative medicine paradigm. Clin Transl Sci. 1:168–171.PubMedGoogle Scholar
  75. Nelson TJ, Behfar A, Terzic A (2008b) Stem cells: biologics for regeneration. Clin Pharmacol Ther 84:620–623.PubMedGoogle Scholar
  76. Nelson TJ, Faustino RS, Chiriac A et al (2008c) CXCR4+/FLK-1+ biomarkers select a cardiopoietic lineage from embryonic stem cells. Stem Cells 26:1464–1473.PubMedGoogle Scholar
  77. Nelson TJ, Terzic A (2009) Induced pluripotent stem cells: reprogrammed without a trace. Regen Med 4:333–355.PubMedGoogle Scholar
  78. Nelson TJ, Behfar A, Terzic A (2009a) Regenerative medicine and stem cell therapeutics. In: pharmacology and therapeutics - principles to practice. Edited by SA Waldman and A Terzic, Saunders Elsevier.Google Scholar
  79. Nelson TJ, Behfar A, Yamada S et al (2009b) Stem cell platforms for regenerative medicine. Clin Transl Sci 2:222–227.PubMedGoogle Scholar
  80. Nelson TJ, Martinez-Fernandez A, Terzic A (2009c) KCNJ11 knockout morula re-engineered by stem cell diploid aggregation. Philos Trans R Soc Lond B Biol Sci 364:269–276.PubMedGoogle Scholar
  81. Nelson TJ, Martinez-Fernandez A, Yamada S et al (2009d) Induced pluripotent stem cells: Advances to applications. Stem Cells and Cloning: Advances and Applications. In press.Google Scholar
  82. Nelson TJ, Martinez-Fernandez A, Yamada S et al (2009e) Repair of acute myocardial infarction with human stemness factors induced pluirpotent stem cells. Circulation 120:408–416.PubMedGoogle Scholar
  83. Nishikawa S, Goldstein RA, Nierras CR (2008) The promise of human induced pluripotent stem cells for research and therapy. Nat Rev Mol Cell Biol 9:725–729.PubMedGoogle Scholar
  84. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448,313–317.PubMedGoogle Scholar
  85. Okita K, Nakagawa M, Hyenjong H et al (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953.PubMedGoogle Scholar
  86. 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):S42–55.PubMedGoogle Scholar
  87. Oyer PE, Stinson EB, Jamieson SA et al (1983) Cyclosporin A in cardiac allografting: a preliminary experience. Transplant Proc 15:1247.Google Scholar
  88. Papapetrou EP, Tomishima MJ, Chambers SM et al (2009) Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proc Natl Acad Sci USA 106:12759–12764.PubMedGoogle Scholar
  89. Park IH, Arora N, Huo H et al (2008a) Disease-specific induced pluripotent stem cells. Cell 134:877–886.PubMedGoogle Scholar
  90. Park IH, Lerou PH, Zhao R et al (2008b) Generation of human-induced pluripotent stem cells. Nat Protoc 3:1180–1186.PubMedGoogle Scholar
  91. Park IH, Zhao R, West JA et al (2008c) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146.PubMedGoogle Scholar
  92. Perin EC, Dohmann HF, Borojevic R et al (2004) Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 110(Suppl 1):II213–8.PubMedGoogle Scholar
  93. Quaini F, Urbanek K, Beltrami AP et al (2002) Chimerism of the transplanted heart. N Engl J Med 346: 5–15.PubMedGoogle Scholar
  94. Raya A, Rodríguez-Pizà I, Guenechea G et al (2009) Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460:53–59.PubMedGoogle Scholar
  95. Rosamond W, Flegal K, Furie K et al (2008)American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 117:e25–146.PubMedGoogle Scholar
  96. Rose EA, Moskowitz AJ, Packer M et al (1999) The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg 67:723–730.PubMedGoogle Scholar
  97. Rosenthal N (2003) Prometheus’s vulture and the stem-cell promise. N Engl J Med 349:267–274.PubMedGoogle Scholar
  98. Rupp S, Koyanagi M, Iwasaki M et al (2008) Characterization of long-term endogenous cardiac repair in children after heart transplantation. Eur Heart J 29:1867–1872.PubMedGoogle Scholar
  99. Sánchez PL, San Román JA, Villa A et al (2006) Contemplating the bright future of stem cell therapy for cardiovascular disease. Nat Clin Pract Cardiovasc Med 3 (Suppl 1):S138–151.PubMedGoogle Scholar
  100. Schächinger 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. 44:1690–1699.PubMedGoogle Scholar
  101. Schächinger V, Erbs S, Elsässer A et al (2006) REPAIR-AMI Investigators. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221.PubMedGoogle Scholar
  102. Schenke-Layland K, Rhodes KE, Angelis E et al (2008) Reprogrammed mouse fibroblasts differentiate into cells of the cardiovascular and hematopoietic lineages. Stem Cells 26:1537–1546.PubMedGoogle Scholar
  103. Schneider JS, Vitale JM, Terzic A et al (2009) Blastocyst injection of embryonic stem cells: A simple approach to unveil mechanisms of corrections in mouse models of human disease. Stem Cell Rev Rep 5:369–77.Google Scholar
  104. Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451:937–942.PubMedGoogle Scholar
  105. Sha HY, Chen JQ, Chen J et al (2009) Fates of donor and recipient mitochondrial DNA during generation of interspecies SCNT-derived human ES-like cells. Cloning Stem Cells 11:497–507.PubMedGoogle Scholar
  106. Shi Y, Desponts C, Do JT et al (2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3:568–574.PubMedGoogle Scholar
  107. Silva J, Nichols J, Theunissen TW et al (2009) Nanog is the gateway to the pluripotent ground state. Cell 138:722–737.PubMedGoogle Scholar
  108. Srinivas G, Anversa P, Frishman WH (2009) Cytokines and myocardial regeneration: a novel treatment option for acute myocardial infarction. Cardiol Rev 17:1–9.PubMedGoogle Scholar
  109. Stadtfeld M, Nagaya M, Utikal J et al (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949.PubMedGoogle Scholar
  110. Stillwell E, Vitale J, Zhao Q et al (2009) Blastocyst injection of wild type embryonic stem cells induces global corrections in mdx mice. PLoS One 4(3):e4759.PubMedGoogle Scholar
  111. Takeuchi JK, Bruneau BG (2009) Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459:708–711.PubMedGoogle Scholar
  112. Sun N, Panett NJ, Gupt DM et al (2009) Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proc Natl Acad Sci USA 106:15720–15725.PubMedGoogle Scholar
  113. Surani MA, McLaren A (2006) Stem cells: a new route to rejuvenation. Nature 443:284–285.PubMedGoogle Scholar
  114. Takahashi K, Yamanaka S al (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676.PubMedGoogle Scholar
  115. Takahashi K, Okita K, Nakagawa M et al (2007a) Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2:3081–3089.PubMedGoogle Scholar
  116. Takahashi K, Tanabe K, Ohnuki M et al (2007b) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872.PubMedGoogle Scholar
  117. Tam PP, Rossant J (2003) Mouse embryonic chimeras: tools for studying mammalian development. Development 130:6155–6163.PubMedGoogle Scholar
  118. Taylor DO, Edwards LB, Aurora P et al (2008) Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report--2008. J Heart Lung Transplant. 27:943–956.PubMedGoogle Scholar
  119. Torella D, Ellison GM, Méndez-Ferrer S et al (2006) Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med 3 (Suppl 1):S8–13.PubMedGoogle Scholar
  120. 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 102:8692–8697.PubMedGoogle Scholar
  121. Utikal J, Polo JM, Stadtfeld M et al (2009) Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460:1145–1148.PubMedGoogle Scholar
  122. Wakayama T, Tabar V, Rodriguez I et al (2001) Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 292:740–743.PubMedGoogle Scholar
  123. Waldman SA, Terzic A (2007) Individualized medicine and the imperative of global health. Clin Pharmacol Ther 82:479–483.PubMedGoogle Scholar
  124. Waldman SA, Terzic MR, Terzic A (2007) Molecular medicine hones therapeutic arts to science. Clin Pharmacol The 82:343–347.PubMedGoogle Scholar
  125. Waldman SA, Terzic A (2008) Therapeutic targeting: a crucible for individualized medicine. Clin Pharmacol Ther 83:651–654.PubMedGoogle Scholar
  126. Wernig M, Zhao JP, Pruszak J et al (2008) Neurons derived from reprogrammed fibroblasts ­functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 105:5856–5861.PubMedGoogle Scholar
  127. Woltjen K, Michael IP, Mohseni P et al (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770.PubMedGoogle Scholar
  128. Wood SA, Allen ND, Rossant J et al (1993a) Non-injection methods for the production of embryonic stem cell-embryo chimaeras. Nature 365:87–89.PubMedGoogle Scholar
  129. Wood SA, Pascoe WS, Schmidt C et al (1993b) Simple and efficient production of embryonic stem cell-embryo chimeras by coculture. Proc Natl Acad Sci USA 90:4582–4585.PubMedGoogle Scholar
  130. Xu D, Alipio Z, Fink LM et al (2009) Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc Natl Acad Sci USA 106:808–813.PubMedGoogle Scholar
  131. Yamada S, Nelson TJ, Behfar A et al (2009) Stem cell transplant into preimplantation embryo yields myocardial infarction-resistant adult phenotype. Stem Cells 27:1697–1705.PubMedGoogle Scholar
  132. Yamanaka S (2007) Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell 1:39–49.PubMedGoogle Scholar
  133. Yamanaka S al (2008) Pluripotency and nuclear reprogramming. Philos Trans R Soc Lond B Biol Sci 363:2079–2087.PubMedGoogle Scholar
  134. Yamanaka S al (2009a) A fresh look at iPS cells. Cell 137:13–17.PubMedGoogle Scholar
  135. Yamanaka S (2009b) Ekiden to iPS Cells. Nat Med 15:1145–1148.PubMedGoogle Scholar
  136. Yamanaka S (2009c) Elite and stochastic models for induced pluripotent stem cell generation. Nature 460:49–52.PubMedGoogle Scholar
  137. Yang L, Soonpaa MH, Adler ED et al (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453:524–852.PubMedGoogle Scholar
  138. Yang X, Smith SL, Tian XC et al (2007) Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nat Genet 39:295–302.PubMedGoogle Scholar
  139. Ye Z, Zhan H, Mali P et al (2009) Human induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood. 2009; in press.Google Scholar
  140. Yokoo N, Baba S, Kaichi S et al (2009) The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells. Biochem Biophys Res Commun 387:482–488.PubMedGoogle Scholar
  141. Yu J, Hu K, Smuga-Otto K et al (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801.PubMedGoogle Scholar
  142. Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920.PubMedGoogle Scholar
  143. Zhao XY, Li W, Lv Z et al (2009) iPS cells produce viable mice through tetraploid complementation. Nature 461:86–90.PubMedGoogle Scholar
  144. Zhang J, Wilson GF, Soerens AG et al (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104:e30–e41.PubMedGoogle Scholar
  145. Zhou H, Wu S, Joo JY et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384.PubMedGoogle Scholar

Copyright information

© Springer Netherlands 2011

Authors and Affiliations

  • Timothy J. Nelson
    • 1
  • Almudena Martinez-Fernandez
    • 1
  • Satsuki Yamada
    • 1
  • Andre Terzic
    • 1
  1. 1.Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical GeneticsMayo ClinicRochesterUSA

Personalised recommendations