Current Problems in Cardiology
Volume 33, Issue 3 , Pages 91-153 , March 2008

Myocardial Regeneration and Stem Cell Repair

References 

  1. Clark EB. Functional Aspects of Cardiac Development (Growth of the Heart in Health and Disease). New York: Raven; 1984;
  2. Rakusan K. Assessment of Cardiac Growth (Growth of the Heart in Health and Disease). New York: Raven; 1984;
  3. Anversa P, Olivetti G. Cellular basis of physiological and pathological myocardial growth. In: Handbook of Physiology. The Cardiovascular System. The Heart. Bethesda, MD: Am. Physiol. Soc., sect. 2, chapt. 2, 2002. p. 75-144.
  4. Anversa P, Ricci R, Olivetti G. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. J Am Coll Cardiol. 1986;7:1140–1149
  5. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–776
  6. Hierlihy AM, Seale P, Lobe CG, et al. The post-natal heart contains a myocardial stem cell population. FEBS Lett. 2002;530:239–243
  7. Martin CM, Meeson AP, Robertson SM, et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol. 2004;265:262–275
  8. Matsuura K, Nagai T, Nishigaki N, et al. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem. 2004;279:11384–11391
  9. Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95:911–921
  10. Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA. 2003;100:12313–12318
  11. Anversa P. Myocyte death in the pathological heart. Circ Res. 2000;86:121–124
  12. Anversa P, Kajstura J. Myocyte cell death in the diseased heart. Circ Res. 1998;82:1231–1233
  13. Anversa P, Leri A, Kajstura J, et al. Myocyte growth and cardiac repair. J Mol Cell Cardiol. 2002;34:91–105
  14. Anversa P, Nadal-Ginard B. Myocyte renewal and ventricular remodelling. Nature. 2002;415:240–243
  15. Nadal-Ginard B, Kajstura J, Leri A, et al. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res. 2003;92:139–150
  16. Agah R, Kirshenbaum LA, Abdellatif M, et al. Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo. J Clin Invest. 1997;100:2722–2728
  17. Chien KR, Olson EN. Converging pathways and principles in heart development and disease. Cell. 2002;110:153–162
  18. MacLellan WR, Schneider MD. Genetic dissection of cardiac growth control pathways. Annu Rev Physiol. 2000;62:289–319
  19. Nakamura T, Schneider MD. The way to a human’s heart is through the stomach: visceral endoderm-like cells drive human embryonic stem cells to a cardiac fate. Circulation. 2003;107:2638–2639
  20. Oh H, Schneider MD. The emerging role of telomerase in cardiac muscle cell growth and survival. J Mol Cell Cardiol. 2002;34:717–724
  21. Oh H, Wang SC, Prahash A, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci USA. 2003;100:5378–5383
  22. Olson EN, Schneider MD. Sizing up the heart: development redux in disease. Genes Dev. 2003;17:1937–1956
  23. Anversa P, Kajstura J, Nadal-Ginard B, et al. Primitive cells and tissue regeneration. Circ Res. 2003;92:579–582
  24. Anversa P, Sussman MA, Bolli R. Molecular genetic advances in cardiovascular medicine: focus on the myocyte. Circulation. 2004;109:2832–2838
  25. Nadal-Ginard B, Kajstura J, Anversa P, et al. A matter of life and death: cardiac myocyte apoptosis and regeneration. J Clin Invest. 2003;111:1457–1459
  26. Anversa P, Palackal T, Sonnenblick EH, et al. Hypertensive cardiomyopathy: myocyte nuclei hyperplasia in the mammalian rat heart. J Clin Invest. 1990;85:994–997
  27. Urbanek K, Quaini F, Tasca G, et al. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA. 2003;100:10440–10445
  28. Beltrami CA, Finato N, Rocco M, et al. Structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation. 1994;89:151–163
  29. Beltrami CA, Finato N, Rocco M, et al. The cellular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol. 1995;27:291–305
  30. Braz JC, Gregory K, Pathak A, et al. PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med. 2004;10:248–254
  31. Chimenti C, Kajstura J, Torella D, et al. Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res. 2003;93:604–613
  32. Torella D, Rota M, Nurzynska D, et al. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res. 2004;94:514–524
  33. Leong FT, Freeman LJ. Acute renal infarction. J R Soc Med. 2005;98:121–122
  34. Lopez LR, Shocket AL, Stanford RE, et al. Gastro-intestinal involvement in leukocytoclastic vasculitis and polyarteritis nodosa. J Rheumatol. 1980;7:677–684
  35. Saegusa M, Takano Y, Okudaira M. Human hepatic infarction: histopathological and postmortem angiological studies. Liver. 1993;13:239–245
  36. Watanabe K, Abe H, Mishima T, et al. Polyangitis overlap syndrome: a fatal case combined with adult Henoch-Schonlein purpura and polyarteritis nodosa. Pathol Int. 2003;53:569–573
  37. Leor J, Patterson M, Quinones MJ, et al. Transplantation of fetal myocardial tissue into the infarcted myocardium of rat (A potential method for repair of infarcted myocardium?). Circulation. 1996;94:II332–II336
  38. Reinecke H, Zhang M, Bartosek T, et al. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation. 1999;100:193–202
  39. Soonpaa MH, Koh GY, Klug MG, et al. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science. 1994;264:98–101
  40. Zhang M, Methot D, Poppa V, et al. Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol. 2001;33:907–921
  41. Menasche P, Hagege AA, Scorsin M, et al. Myoblast transplantation for heart failure. Lancet. 2001;347:279–280
  42. Murry CE, Wiseman RW, Schwartz SM, et al. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest. 1996;98:2512–2523
  43. Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998;4:929–933
  44. Condorelli G, Borello U, De Angelis L, et al. Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: implication for myocardium regeneration. Proc Natl Acad Sci USA. 2001;98:10733–10738
  45. Etzion S, Battler A, Barbash IM, et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol Cell Cardiol. 2001;33:1321–1330
  46. Hattan N, Kawaguchi H, Ando K, et al. Purified cardiomyocytes from bone marrow mesenchymal stem cells produce stable intracardiac grafts in mice. Cardiovasc Res. 2005;65:334–344
  47. Galli D, Innocenzi A, Staszewsky L, et al. Mesoangioblasts, vessel-associated multipotent stem cells, repair the infarcted heart by multiple cellular mechanisms (A comparison with bone marrow progenitors, fibroblasts, and endothelial cells). Arterioscler Thromb Vasc Biol. 2005;25:692–697
  48. Li RK, Jia ZQ, Weisel RD, et al. Smooth muscle cell transplantation into myocardial scar tissue improves heart function. J Mol Cell Cardiol. 1999;31:513–522
  49. Fernandez-Aviles F, San Roman JA, Garcia-Frade J, et al. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res. 2004;95:742–748
  50. 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
  51. Kawada H, Fujita J, Kinjo K, et al. Non-hematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood. 2004;104:3581–3587
  52. Kajstura J, Rota M, Whang B, et al. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res. 2005;96:127–137
  53. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–705
  54. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair in infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001;98:10344–10349
  55. Yoon YS, Wecker A, Heyd L, et al. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest. 2005;115:326–338
  56. Zhang S, Wang D, Estrov Z, et al. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation. 2004;110:3803–3807
  57. Behfar A, Zingman LV, Hodgson DM, et al. Stem cell differentiation requires a paracrine pathway in the heart. FASEB J. 2002;16:1558–1566
  58. Linke A, Müller P, Nurzynska D, et al. Cardiac stem cells in the dog heart regenerate infarcted myocardium improving cardiac performance. Proc Natl Acad Sci USA. 2005;102:8966–8971
  59. Nurzynska D, Whang B, Rota M, et al. Cardiac stem cell activation and myocardial regeneration reverse heart failure and prolong the lifespan of senescent Fischer 344 rats. Circulation. 2004;110:III-171
  60. Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001;19:193–204
  61. Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci. 2000;113:5–10
  62. Reubinoff BE, Pera M, Fong CY, et al. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotech. 2000;18:399–404
  63. Thomson JA, Eldor JI, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–1147
  64. Beddington RS, Robertson EJ. An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development. 1989;105:733–737
  65. Chambers I, Smith A. Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene. 2004;23:7150–7160
  66. Wobus AM, Guan K, Pich U. In vitro differentiation of embryonic stem cells and analysis of cellular phenotypes. Methods Mol Biol. 2002;158:263–286
  67. Doss MX, Koehler CI, Gissel C, et al. Embryonic stem cells: a promising tool for cell replacement therapy. J Cell Mol Med. 2004;8:465–473
  68. Kehat I, Gepstein L. Human embryonic stem cells for myocardial regeneration. Heart Fail Rev. 2003;8:229–236
  69. Pera MF, Trounson AO. Human embryonic stem cells: prospects for development. Development. 2004;131:5515–5525
  70. Desbaillets I, Ziegler U, Groscurth P, et al. Embryoid bodies: an in vitro model of mouse embryogenesis. Exp Physiol. 2000;85:645–651
  71. Itskovitz-Eldor JI, Schuldiner M, Karsenti D, et al. Differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers. Mol Med. 2000;6:88–95
  72. Karbanova J, Mokry J. Histological and histochemical analysis of embryoid bodies. Acta Histochem. 2002;104:361–365
  73. Hamazaki T, Oka M, Yamanaka S, et al. Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation. J Cell Sci. 2004;117:5681–5686
  74. Bader A, Gruss A, Hollrigl A, et al. Paracrine promotion of cardiomyogenesis in embryoid bodies by LIF modulated endoderm. Differentiation. 2001;68:31–43
  75. Kehat I, Kenyagin KD, Snir M, et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest. 2001;108:407–414
  76. Takada T, Suzuki Y, Kondo Y, et al. Monkey embryonic stem cell lines expressing green fluorescent protein. Cell Transplant. 2002;11:631–635
  77. Andrews PW. From teratocarcinomas to embryonic stem cells. Philos Trans R Soc Lond B Biol Sci. 2002;357:405–417
  78. Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113:643–655
  79. Hatano SY, Tada M, Kimura H, et al. Pluripotential competence of cells associated with Nanog activity. Mech Dev. 2005;122:67–79
  80. Okumura-Nakanishi S, Saito M, Niwa H, et al. Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem. 2005;280:5307–5317
  81. Pan GJ, Chang ZY, Scholer HR, et al. Stem cell pluripotency and transcription factor Oct 4. Cell Res. 2002;12:321–329
  82. Hart AH, Hartley L, Ibrahim M, et al. Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. Dev Dyn. 2004;230:187–198
  83. Tai MH, Chang CC, Olson LK, et al. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26:495–502
  84. Draper JS, Fox V. Human embryonic stem cells: multilineage differentiation and mechanisms of self-renewal. Arch Med Res. 2003;34:558–564
  85. Hodgson DM, Behar A, Zingman LV, et al. Stable benefit of embryonic stem cell therapy in myocardial infarction. Am J Physiol Heart Circ Physiol. 2004;287:H471–H479
  86. Kofidis T, deBruin JL, Yamane T, et al. IGF-1 promotes engraftment, differentiation and functional improvement after transfer of embryonic stem cells for myocardial restoration. Stem Cells. 2004;22:1239–1245
  87. Kofidis T, deBruin JL, Yamane T, et al. Stimulation of paracrine pathways with growth factors enhances embryonic stem cell engraftment and host-specific differentiation in the heart after ischemic myocardial injury. Circulation. 2005;111:2486–2493
  88. Min JY, Yang Y, Converso KL, et al. Transplantation of embryonic stem cells improves cardiac function in post-infarcted rats. J Appl Physiol. 2002;92:288–296
  89. Min JY, Yang Y, Sullivan MF, et al. Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells. J Thorac Cardiovasc Surg. 2003;125:361–369
  90. Wang JF, Yang Y, Wang G, et al. Embryonic stem cells attenuate viral myocarditis in murine models. Cell Transplant. 2002;11:753–758
  91. Levenberg S, Golub JS, Amit M, et al. Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci USA. 2002;99:4391–4396
  92. Kehat I, Khimovich L, Caspi O, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotech. 2004;10:1–8
  93. Lum LG, Padbury JF, Davol PA, et al. Virtual reality of stem cell transplantation to repair injured myocardium. J Cell Biochem. 2007;(in press)
  94. Yang Y, Min JY, Rana JS, et al. VEGF enhances functional improvement of post-infarcted hearts by transplantation of ESC-differentiated cells. J Appl Physiol. 2002;93:1140–1151
  95. Yuasa S, Itabashi Y, Koshimizu U, et al. Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Nat Biotechnol. 2005;23:607–611
  96. Tzukerman M, Rosenberg T, Ravel Y, et al. An experimental platform for studying growth and invasiveness of tumor cells within teratomas derived from human embryonic stem cells. Proc Natl Acad Sci USA. 2003;100:13507–13512
  97. 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
  98. Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res. 2002;91:189–201
  99. Heng BC, Haider HK, Sim EK, et al. Comments about possible use of human embryonic stem cell-derived cardiomyocytes to direct autologous adult stem cells into the cardiomyogenic lineage. Acta Cardiol. 2005;60:7–12
  100. Wenzel F, Dittrich M, Hescheler J, et al. Hypoxia influences generation and propagation of electrical activity in embryonic cardiomyocyte clusters. Comp Biochem Physiol A Mol Integr Physiol. 2002;132:111–115
  101. Zhou X, Quann E, Gallicano GI. Differentiation of non-beating embryonic stem cells into beating cardiomyocytes is dependent on downregulation of PKC beta and zeta in concert with upregulation of PKC epsilon. Dev Biol. 2003;255:407–422
  102. Schulinder M, Yanuka O, Itskovitz-Elder J, et al. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci USA. 2000;97:11307–11312
  103. Fijvandraat AC, vanGinneken AC, de Boer PA, et al. Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube. Cardiovasc Res. 2003;58:399–409
  104. Drukker M, Benvenisty N. The immunogenicity of human embryonic stem-derived cells. Trends Biotechnol. 2004;22:136–141
  105. Sheikh AY, Yang PC, Wu JC, et al. Embryonic stem cells and myocardial regeneration. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 105–116
  106. Draper JS, Pigott C, Thomson JA, et al. Surface antigens of human embryonic stem cells: changes upon differentiation in culture. J Anat. 2002;200:249–258
  107. Martin MJ, Muotri A, Gage F, et al. Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med. 2005;11:228–232
  108. a. Kamp TJ, Lyons GE. Embryonic stem cells and cardiogenesis. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 25–35
  109. Wills SE. Federal funding of human embryonic stem cell research—illegal, unethical and unnecessary. J Contemp Health Law Policy. 2001;18:95–145
  110. Fishbach GD, Fishbach RL. Stem cells: science, policy, and ethics. J Clin Invest. 2004;114:1364–1370
  111. Gilbert DM. The future of embryonic stem cell research: addressing ethical conflict with responsible scientific research. Med Sci Monit. 2004;10:99–103
  112. Lysaght MJ, Hazlehurst AL. Private sector development of stem cell technology and therapeutic cloning. Tissue Eng. 2003;9:555–561
  113. Landry DW, Zucker HA. Embryonic death and the creation of human embryonic stem cells. J Clin Invest. 2004;114:1184–1186
  114. Hardy K, Spanos S, Becker D, et al. From cell death to embryo arrest: mathematical models of human preimplantation embryo development. Proc Natl Acad Sci USA. 2001;98:1655–1660
  115. Laverge H, Van der Elst J, De Sutter P, et al. Fluorescent in-situ hybridization on human embryos showing cleavage arrest after freezing and thawing. Hum Reprod. 1998;13:425–429
  116. Vogel G, Holden C. Field leaps forward with new stem cell advances. Science. 2007;318:1224–1225
  117. Nadin BM, Goodell MA, Hirschi KK. Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood. 2003;102:2436–2443
  118. Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol. 2001;17:387–403
  119. Shizuru JA, Negrin RS, Weissman IL. Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system. Annu Rev Med. 2005;56:509–538
  120. Christoffels VM, Burch JB, Moorman AF. Architectural plan for the heart: early patterning and delineation of the chambers and the nodes. Trends Cardiovasc Med. 2004;14:301–307
  121. Eisenberg CA, Eisenberg LM. WNT11 promotes cardiac tissue formation of early mesoderm. Dev Dyn. 1999;216:45–58
  122. Eisenberg LM, Kubalak SW, Eisenberg CA. Stem cells and the formation of the myocardium in the vertebrate embryo. Anat Rec A Discov Mol Cell Evol Biol. 2004;276:2–12
  123. Eisenberg LM, Burns L, Eisenberg CA. Hematopoietic cells from bone marrow have the potential to differentiate into cardiomyocytes in vitro. Anat Rec A Discov Mol Cell Evol Biol. 2003;274:870–882
  124. Slack JM, Tosh D. Transdifferentiation and metaplasia—switching cell types. Curr Opin Genet Dev. 2001;11:581–586
  125. Tosh D, Shen CN, Slack JM. Differentiated properties of hepatocytes induced from pancreatic cells. Hepatology. 2002;36:534–543
  126. Tosh D, Shen CN, Slack JM. Conversion of pancreatic cells to hepatocytes. Biochem Soc Trans. 2002;30:51–55
  127. Tosh D, Slack JM. How cells change their phenotype. Nat Rev Mol Cell Biol. 2002;3:187–194
  128. Beresford WA. Direct transdifferentiation: can cells change their phenotype without dividing?. Cell Differ Dev. 1990;29:81–93
  129. Eguchi G, Kodama R. Transdifferentiation. Curr Opin Cell Biol. 1993;5:1023–1028
  130. Shen CN, Horb ME, Slack JM, et al. Transdifferentiation of pancreas to liver. Mech Dev. 2003;120:107–116
  131. Lanza RP, Cibelli JB, West MD. Prospects for the use of nuclear transfer in human transplantation. Nat Biotechnol. 1999;17:1171–1174
  132. Lanza RP, Cibelli JB, West MD. Human therapeutic cloning. Nat Med. 1999;5:975–977
  133. Miyoshi K, Shillingford JM, Le Provost F, et al. Activation of beta-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. Proc Natl Acad Sci USA. 2002;99:219–224
  134. Alison MR, Poulsom R, Otto WR, et al. Recipes for adult stem cell plasticity: fusion cuisine or readymade?. J Clin Pathol. 2004;57:113–120
  135. Grove JE, Bruscia E, Krause DS. Plasticity of bone marrow-derived stem cells. Stem Cells. 2004;22:487–500
  136. Quesenberry PJ, Abedi M, Aliotta J, et al. Stem cell plasticity: an overview. Blood Cells Mol Dis. 2004;32:1–4
  137. Camargo FD, Finegold M, Goodell MA. Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J Clin Invest. 2004;113:1266–1270
  138. Camargo FD, Green R, Capetanaki Y, et al. Stem cell plasticity: from transdifferentiation to macrophage fusion. Cell Prolif. 2004;37:55–65
  139. Doyonnas R, LaBarge MA, Sacco A, et al. Hematopoietic contribution to skeletal muscle regeneration by myelomonocytic precursors. Proc Natl Acad Sci USA. 2004;101:13507–13512
  140. Eisenberg LM, Eisenberg CA. An in vitro analysis of myocardial potential indicates that phenotypic plasticity is an innate property of early embryonic tissue. Stem Cells Dev. 2004;13:614–624
  141. Lanza R, Moore MA, Wakayama T, et al. Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circ Res. 2004;94:820–827
  142. Lanza R, Rosenthal N. The stem cell challenge. Sci Am. 2004;290:92–99
  143. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res. 2004;95:9–20
  144. Suva D, Garavaglia G, Menetrey J, et al. Non-haematopoietic human bone marrow contains long-lasting pluripotential mesenchymal stem cells. J Cell Physiol. 2004;198:110–118
  145. Horwitz EM. Stem cell plasticity: the growing potential of cellular therapy. Arch Med Res. 2003;34:600–606
  146. Koh CJ, Atala A. Tissue engineering, stem cells, and cloning: opportunities for regenerative medicine. J Am Soc Nephrol. 2004;15:1113–1125
  147. Lakshmipathy U, Verfaillie C. Stem cell plasticity. Blood Rev. 2005;19:29–38
  148. Mathur A, Martin JF. Stem cells and repair of the heart. Lancet. 2004;364:183–192
  149. Mironov V, Visconti RP, Markwald RR. What is regenerative medicine? (Emergence of applied stem cell and developmental biology). Exp Opin Biol Ther. 2004;4:773–781
  150. Prockop DJ, Gregory CA, Spees JL. One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc Natl Acad Sci USA. 2003;100:11917–11923
  151. Theise ND, d’Inverno M. Understanding cell lineages as complex adaptive systems. Blood Cells Mol Dis. 2004;32:17–20
  152. Tsonis PA. Regenerative biology: the emerging field of tissue repair and restoration. Differentiation. 2002;70:397–409
  153. Borue X, Lee S, Grove J, et al. Bone marrow-derived cells contribute to epithelial engraftment during wound healing. Am J Pathol. 2004;165:1767–1772
  154. Brittan M, Braun KM, Reynolds LE, et al. Bone marrow cells engraft within the epidermis and proliferate in vivo with no evidence of cell fusion. J Pathol. 2005;205:1–13
  155. Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA. 1997;194:4080–4085
  156. Ianus A, Holz GG, Theise ND, et al. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 2003;111:843–850
  157. Lin F, Cordes K, Li L, et al. Bone marrow stem cells contribute to healing of the kidney. J Am Soc Nephrol. 2003;14:S48–S54
  158. Palermo AT, Labarge MA, Doyonnas R, et al. Bone marrow contribution to skeletal muscle: a physiological response to stress. Dev Biol. 2005;279:336–344
  159. Poulsom R, Alison MR, Cook T, et al. Bone marrow stem cells contribute to healing of the kidney. J Am Soc Nephrol. 2003;14:S48–S54
  160. Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology. 2000;32:11–16
  161. Becker AJ, McCulloch EA, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963;197:452–454
  162. Siminovitch L, McCulloch EA, Till JE. The distribution of colony-forming cells among spleen colonies. J Cell Physiol. 1963;62:327–336
  163. Till JE, McCulloch EA, Siminovitch L. A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci USA. 1964;51:29–36
  164. Till JE, McCulloch EA, Siminovitch L. Isolation of variant cell lines during serial transplantation of hematopoietic cells derived from fetal liver. J Natl Cancer Inst. 1964;33:707–720
  165. Weissman IL. The road ended up at stem cells. Immunol Rev. 2002;185:159–174
  166. Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science. 1988;241:58–62
  167. Uchida N, Weissman IL. Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin-Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-11 bone marrow. J Exp Med. 1992;175:175–184
  168. Osawa M, Nakamura K, Nishi N, et al. In vivo self-renewal of c Kit+ Sca-1+ Lin(low/-) hematopoietic stem cells. J Immunol. 1996;156:3207–3214
  169. Morrison SJ, Weissman IL. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity. 1994;1:661–673
  170. Morrison SJ, Uchida N, Weissman IL. The biology of hematopoietic stem cells. Annu Rev Cell Dev Biol. 1995;11:35–71
  171. Negrin RS, Atkinson K, Leemhuis T, et al. Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer. Biol Blood Marrow Transplant. 2000;6:262–271
  172. Donnelly DS, Krause DS. Hematopoietic stem cells can be CD34+ or CD34−. Leuk Lymphoma. 2001;40:221–234
  173. Guo Y, Lubbert M, Engelhardt M. CD34- hematopoietic stem cells: current concepts and controversies. Stem Cells. 2003;21:15–20
  174. Bhatia M. AC133 expression in human stem cells. Leukemia. 2001;15:1685–1688
  175. Alison MR, Poulsom R, Otto WR, et al. Plastic adult stem cells: will they graduate from the school of hard knocks?. J Cell Sci. 2003;116:599–603
  176. Forbes SJ, Vig P, Poulsom R, et al. Adult stem cell plasticity: new pathways of tissue regeneration become visible. Clin Sci. 2002;103:355–369
  177. Vescovi A, Gritti A, Cossu G, et al. Neural stem cells: plasticity and their transdifferentiation potential. Cells Tissues Organs. 2002;171:64–76
  178. 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
  179. Wagers AJ, Sherwood RI, Christensen JL, et al. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002;297:2256–2259
  180. Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell. 2004;116:639–648
  181. Wells WA. Is transdifferentiation in trouble?. J Cell Biol. 2002;157:15–18
  182. Davani S, Deschaseaux F, Chalmers D, et al. Can stem cells mend a broken heart?. Cardiovasc Res. 2005;65:305–316
  183. Eisenberg LM, Eisenberg CA. Adult stem cells and their cardiac potential. Anat Rec A Discov Mol Cell Evol Biol. 2004;276:103–112
  184. Mezey E. Commentary: on bone marrow stem cells and openmindedness. Stem Cells Dev. 2004;13:147–152
  185. Eisenberg LM, Eisenberg CA. Stem cell plasticity, cell fusion, and transdifferentiation. Birth Defects Res C Embryo Today. 2003;69:209–218
  186. Heil M, Ziegelhoeffer T, Mees B, et al. A different outlook on the role of bone marrow stem cells in vascular growth: bone marrow delivers software not hardware. Circ Res. 2004;94:573–574
  187. Korbling M, Estrov Z. Adult stem cells and tissue repair. Bone Marrow Transplant. 2003;32:S23–S24
  188. Rota M, Hosoda T, Bearzi C, et al. Formation of temporary niches is required for bone marrow cells to adopt the cardiomyogenic fate in vivo. (abst) Circulation. 2007;116:II-38
  189. Liao R, Pfister O, Jain M, et al. The bone marrow-cardiac axis of myocardial regeneration. Prog Cardiovasc Dis. 2007;50:18–30
  190. Assmus B, Schachinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002;106:3009–3017
  191. Britten MB, Abolmaali ND, Assmus B, et al. 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. 2003;108:2212–2218
  192. Fuchs S, Satler LF, Kornowski R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol. 2003;41:1721–1724
  193. Galinanes M, Loubani M, Davies J, et al. Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans. Cell Transplant. 2004;13:7–13
  194. Hamano K, Nishida M, Hirata K, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischaemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001;65:845–847
  195. Li TS, Hamano K, Hirata K, et al. The safety and feasibility of the local implantation of autologous bone marrow cells for ischemic heart disease. J Card Surg. 2003;18:S69–S75
  196. Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107:2294–2302
  197. Perin EC, Dohmann HF, Borojevic R, et al. Improved exercise capacity and ischemia 6 and 12 mo after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation. 2004;110:213–218
  198. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004;44:1690–1699
  199. Seiler C, Pohl T, Wustmann K, et al. Promotion of collateral growth by GM-CSF in patients with coronary artery disease: a randomised double blind placebo-controlled study. Circulation. 2001;104:2012–2015
  200. Stamm C, Kleine HD, Westphal B, et al. CABG and bone marrow stem cell transplantation after myocardial infarction. J Thorac Cardiovasc Surg. 2004;52:152–158
  201. Stamm C, Westphal B, Kleine HD, et al. Autologous bone marrow stem cell transplantation for myocardial regeneration. Lancet. 2003;361:45–46
  202. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106:1913–1918
  203. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomized controlled clinical trial. Lancet. 2004;364:141–148
  204. Lunde K, Solheim S, Aakhus V, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–1209
  205. 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
  206. Assmus B, Honold J, Schachinger V, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006;355:1222–1232
  207. Janssens S, Dubois C, Bogaert J, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomized, controlled trial. Lancet. 2006;367:113–121
  208. Lipinski MJ, Biondi-Zoccai GG, Abbate A, et al. 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. 2007;50:1761–1767
  209. Abdel-Latif A, Bolli R, Tleyjeh IM, et al. Adult bone marrow-derived cells for cardiac repair (A systematic review and meta-analysis). Arch Intern Med. 2007;167:989–997
  210. Angoulvant D, Fazel S, Li RK. Neovascularization derived from cell transplantation in ischemic myocardium. Mol Cell Biochem. 2004;264:133–142
  211. Kinnaird T, Stabile E, Burnett MS, et al. Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences. Circ Res. 2004;95:354–363
  212. Takahashi T, Kalka C, Masuda H, et al. Ischemia and cytokine-induced mobilization of bone marrow-derived progenitor cells for neovascularization. Nat Med. 1999;5:434–438
  213. Norol F, Merlet P, Isnard R, et al. Influence of mobilized stem cells on myocardial infarct repair in a nonhuman primate model. Blood. 2003;102:436–468
  214. Saito T, Kuang JQ, Lin CC, et al. Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovasc Surg. 2003;126:114–123
  215. Lanza F, Latorraca A, Moretti S, et al. Comparative analysis of different permeabilization methods for the flow cytometry measurement of cytoplasmic myeloperoxidase and lysozyme in normal and leukemic cells. Cytometry. 1997;30:134–144
  216. McCay CM, Pope F, Lunsford W, et al. Parabiosis between young and old rats. Gerontologia. 1957;1:7–17
  217. Shake JG, Gruber PJ, Baumgartner WA, et al. Mesenchymal stem cell implantation in a swine myocardial infarcted model: engraftment and functional effects. Ann Thorac Surg. 2002;73:1919–1925
  218. Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 2003;9:1195–1201
  219. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med. 2001;344:1750–1757
  220. Kajstura J, Leri A, Finato N, et al. Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci USA. 1998;95:8801–8805
  221. Soonpaa MH, Field LJ. Survey of studies examining mammalian cardiomyocyte DNA synthesis. Circ Res. 1998;83:15–26
  222. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function?. Cell. 2001;105:829–841
  223. Bolli R. Regeneration of the human heart: no chimera?. N Engl J Med. 2002;346:5–15
  224. Muller P, Pfeiffer P, Koglin J, et al. Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation. 2002;106:31–35
  225. Quaini F, Urbanek K, Beltrami AP, et al. Chimerism of the transplanted heart. N Engl J Med. 2002;346:5–15
  226. Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart. Circ Res. 1998;83:1–14
  227. Deb A, Wang S, Skelding KA, et al. Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation. 2003;107:1247–1249
  228. Glaser R, Lu MM, Narula N, et al. Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts. Circulation. 2002;106:17–19
  229. Thiele J, Varus E, Wickenhauser C, et al. Regeneration of heart muscle tissue: quantification of chimeric cardiomyocytes and endothelial cells following transplantation. Histol Histopathol. 2004;19:201–209
  230. Thiele J, Varus E, Wickenhauser C, et al. Mixed chimerism of cardiomyocytes and vessels after allogenic bone marrow and stem-cell transplantation in comparison with cardiac allografts. Transplantation. 2004;77:1902–1905
  231. Kunisada T, Yoshida H, Yamakazi H, et al. Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors. Development. 1998;125:2915–2923
  232. Teyssier-Le Discorde M, Prost S, et al. Spatial and temporal mapping of c-kit and its ligand, stem cell factor expression during human embryonic haemopoiesis. Br J Haematol. 1999;107:247–253
  233. Iaffaldano G, Misao Y, LeCapitaine N, et al. C-kit positive cardiac progenitor cells contribute to the embryonic development of the heart. (abst) Circulation. 2007;116:II-185
  234. Frangogiannis NG, Perrard JL, Mendoza LH, et al. Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. Circulation. 1998;98:687–698
  235. Barile L, Messina E, Giacomello A, et al. Endogenous cardiac stem cells. Prog Cardiovasc Dis. 2007;50:31–48
  236. Cai J, Weiss ML, Rao MS. In search of “stemness.”. Exp Hematol. 2004;32:585–598
  237. Davey RE, Zandstra PW. Signal processing underlying extrinsic control of stem cell fate. Curr Opin Hematol. 2004;11:95–101
  238. Kondo M, Wagers AJ, Manz MG, et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol. 2003;21:759–806
  239. Civin CI, Loken MR. Cell surface antigens on human marrow cells: dissection of hematopoietic development using monoclonal antibodies and multiparameter flow cytometry. Int J Cell Cloning. 1987;5:267–288
  240. Ferrero D, Gabbianelli M, Peschle C, et al. Surface phenotypes of human hematopoietic progenitor cells defined by monoclonal antibodies. Blood. 1985;66:496–502
  241. Tjonnfjord GE, Steen R, Veiby OP, et al. Haemopoietic progenitor cell differentiation: flow cytometric assessment in bone marrow and thymus. Br J Haematol. 1995;91:1006–1016
  242. Groeneveld K, te Marvelde JG, van den Beemd MW, et al. Flow cytometric detection of intracellular antigens for immunophenotyping of normal and malignant leukocytes. Leukemia. 1996;10:1383–1389
  243. Harvey KA, Siddiqui RA, Jansen J, et al. Growth factor induction of cytosolic protein tyrosine kinase activity in human haemopoietic progenitor cells isolated by flow cytometry. Br J Haematol. 1996;93:515–526
  244. Melan MA. Overview of cell fixatives and cell membrane permeants. Methods Mol Biol. 1999;115:45–55
  245. Montero C. The antigen-antibody reaction in immunohistochemistry. J Histochem Cytochem. 2003;51:1–4
  246. Srinivasan M, Sedmak D, Jewell S. Effects of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol. 2002;161:1961–1971
  247. Asakura A, Seale P, Girgis-Gabardo A, et al. Myogenic specification of side population cells in skeletal muscle. J Cell Biol. 2002;159:123–134
  248. Bunting KD. ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells. 2002;20:11–20
  249. Goodell MA, McKinney-Freeman S, Camargo FD. Isolation and characterization of side population cells. Methods Mol Biol. 2005;290:343–352
  250. McKinney-Freeman SL, Jackson KA, Camargo FD, et al. Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci USA. 2002;99:1341–1346
  251. Zhou S, Schuetz JD, Bunting KD, et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001;7:1028–1034
  252. Wilson R, Chen X, Kubo H, et al. Phenotype and function of c-kit+-derived amplifying myocytes. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 77–85
  253. Campos LS. Neurospheres: insights into neural stem cell biology. J Neurosci Res. 2004;78:761–769
  254. Dawn B, Stein AB, Urbanek K, et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci USA. 2005;102:3766–3771
  255. Germani A, Limana F, Capogrossi MC. Activation of the local regenerative system of the heart. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 95–102
  256. Tang YL, Shen L, Qian K, et al. A novel two-step procedure to expand cardiac Sca-l+ cells clonally. Biochem Biophys Res Commun. 2007;359:877–883
  257. Bunting HD, Zhou S, Lu T, Sorrentino BP. Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo. Blood. 2000;96:902–909
  258. Majka SM, Jackson KA, Kienstra KA, et al. Distinct progenitor populations in skeletal muscle are bone marrow-derived and exhibit different cell fates during vascular regeneration. J Clin Invest. 2003;111:71–79
  259. Zhou S, Zong Y, Lu T, Sorrentino BP. Hematopoietic cells from mice that are deficient in both Bcrp1/Abcg2 and Mdr1a/b develop normally but are sensitized to mitoxantrone. Biotechniques. 2003;35:1248–1252
  260. Gussoni E, Soneoka Y, Strickland CD, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999;401:390–394
  261. Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA. 2005;102:8692–8697
  262. Jackson KA, Majka SM, Wulf GG, et al. Stem cells: a minireview. J Cell Immun Biochem. 2002;38:1–6
  263. Ito CY, Li CY, Bernstein A, et al. Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice. Blood. 2003;101:517–523
  264. Schinkel AH, Mayer U, Wagenaar E, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug transporting) P-glycoproteins. Proc Natl Acad Sci USA. 1997;94:4028–4033
  265. Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988;55:185–192
  266. Nocka K, Majumder S, Chabot B, et al. Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice: evidence for an impaired c-kit kinase in mutant mice. Genes Dev. 1989;3:816–826
  267. Reith AD, Rottapel R, Giddens E, et al. W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit receptor. Genes Dev. 1990;4:390–400
  268. Cable J, Jackson IJ, Steel KP. Mutations at the W locus affect survival of neural crest-derived melanocytes in the mouse. Mech Dev. 1995;50:139–150
  269. Theoharides TC, el-Mansoury M, Letourneau R, et al. Dermatitis characterized by mastocytosis at immunization sites in mast-cell-deficient W/Wv mice. Int Arch Allergy Immunol. 1993;102:352–361
  270. Chi MM, Powley TL. c-kit mutant mouse behavioral phenotype: altered meal patterns and CCK sensitivity but normal daily food intake and body weight. Am J Physiol Regul Integr Comp Physiol. 2003;285:R1170–R1183
  271. Yuan S, Schoenwolf GC. Islet-1 marks the early heart rudiments and is asymmetrically expressed during early rotation of the foregut in the chick embryo. Anat Rec. 2000;260:204–207
  272. Cai CL, Liang X, Shi Y, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5:877–889
  273. Dodou E, Verzi MP, Anderson JP, et al. Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development. 2004;131:3931–3942
  274. Laugwitz KL, Moretti A, Lam J, et al. Postnatal isl1+cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 2005;433:585–587
  275. Mosna F, Bearzi C, Rota M, et al. Origin and therapeutic efficacy of human cardiac progenitor cells. (abst) Circulation. 2007;116:II-104
  276. Bearzi C, LeCapitaine N, Urbanek K, et al. Identification of a human coronary vasculature progenitor cell. (abst) Circulation. 2007;116:II-131
  277. Balsam LB, Wagers AJ, Christensen JL, et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature. 2004;428:668–673
  278. McKinney-Freeman S, Goodell MA. Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis. Exp Hematol. 2004;32:868–876
  279. Tauchi H, Sato T. Changes in hepatic cell mitochondria during parabiosis between old and young rats. Mech Aging Dev. 1980;12:7–14
  280. Conboy IM, Conboy MJ, Wagers AJ, et al. Rejuvenation of aged progenitor cells by exposure to a young systematic environment. Nature. 2005;433:760–764
  281. Conboy IM, Conboy MJ, Smythe GM, et al. A Notch-mediated restoration of regenerative potential to aged muscle. Science. 2003;302:1575–1577
  282. Conboy I, Rando T. Aging, stem cells and tissue regenerationlessons from muscle. Cell Cycle. 2005;4:407–410
  283. Winn N, Paul A, Musaro A, et al. Insulin-like growth factor isoforms in skeletal muscle aging, regeneration, and disease. Cold Spring Harb Symp Quant Biol. 2002;67:507–518
  284. Pandur P. What does it take to make a heart?. Biol Cell. 2005;97:197–210
  285. Keegan BR, Feldman JL, Begemann G, et al. Retinoic acid signaling restricts the cardiac progenitor pool. Science. 2005;307:247–249
  286. Sieber-Blum M. Cardiac neural crest stem cells. Anat Rec. 2004;276:34–42
  287. Solloway MJ, Harvey RP. Molecular pathways in myocardial development: a stem cell perspective. Cardiovasc Res. 2003;58:264–277
  288. Wessels A, Perez-Pomares JM. The epicardium and epicardially derived cells (EPDC’s) as cardiac stem cells. Anat Rec. 2004;276A:43–57
  289. Mikawa T, Fischman DA. The polyclonal origin of myocyte lineages. Annu Rev Physiol. 1996;58:509–521
  290. Meilhac SM, Esner M, Kerszberg M, et al. Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis. J Cell Biol. 2004;164:97–109
  291. Meilhac SM, Kelly RG, Rocancourt D, et al. A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart (The Company of Biologists). Development. 2003;130:3877–3889
  292. Meilhac SM, Esner M, Kelly RG, et al. The clonal origin of myocardial cells in different regions of the embryonic mouse heart. Dev Cell. 2004;6:685–698
  293. Eberhard D, Jockusch H. Patterns of myocardial histogenesis as revealed by mouse chimeras. Dev Biol. 2005;278:336–346
  294. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 2004;116:769–778
  295. Palmer TD. Adult neurogenesis and the vascular Nietzsche. Neuron. 2002;34:856–858
  296. Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol. 2000;425:479–494
  297. Spradling A, Drummond-Barbosa D, Kai T. Stem cells find their niche. Nature. 2001;414:98–104
  298. Tumbar T, Guasch G, Greco V, et al. Defining the epithelial stem cell niche in skin. Science. 2004;303:359–363
  299. Watt FM, Hogan BLM. Out of Eden: stem cells and their niches. Science. 2000;287:1427–1438
  300. Leri A, Boni A, Siggins R, et al. Cardiac stem cells and their niches. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 87–94
  301. Urbanek K, Cesselli D, Rota M, et al. Stem cell niches in the adult mouse heart. Proc Natl Acad Sci USA. 2006;103:9226–9231
  302. LeCapitaine N, Bearzi C, Urbanek K, et al. The mammalian heart contains vascular and myocyte niches. (abst) Circulation. 2007;116:II-226
  303. Allman D, Aster JC, Pear WS. Notch signaling in hematopoiesis and early lymphocyte development. Immunol Rev. 2002;187:75–86
  304. Berdnik D, Torok T, Gonzalez-Gaitan M, et al. The endocytic protein -adaptin is required for numb-mediated asymmetric cell division in Drosophila. Dev Cell. 2002;3:221–231
  305. Campos LS, Leone DP, Relvas JB, et al. 1 Integrins activate a MAPK signaling pathway in neural stem cells that contributes to their maintenance. Development. 2004;131:3433–3444
  306. Estes BT, Gimble JM, Guilak F. Mechanical signals as regulators of stem cell fate. Curr Top Dev Biol. 2004;60:91–126
  307. Hirao A, Arai F, Suda T. Regulation of cell cycle in hematopoietic stem cells by the niche. Cell Cycle. 2004;3:1481–1483
  308. Jafar-Nejad H, Norga K, Bellen H. Numb: “Adapting” Notch for endocytosis. Dev Cell. 2002;3:155–156
  309. Jan YN, Jan LY. Asymmetric cell division. Nat Rev Neurosci. 2001;392:775–778
  310. Estivill-Torrus G, Pearson H, van Heyningen V, et al. Pax 6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors. Development. 2002;129:455–466
  311. Lai EC. Notch signaling: control of cell communication and cell fate. Development. 2004;131:965–973
  312. Arai F, Hirao A, Ohmura M, et al. Tie2/Angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118:149–161
  313. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–846
  314. Lin H. The stem cell niche theory: lessons from flies. Nat Rev Sci. 2002;3:931–940
  315. Ohlstein B, Kai T, Decotto E, et al. The stem cell niche: theme and variations. Curr Opin Cell Biol. 2004;16:693–699
  316. Xie T, Kawase E, Kirilly D, Wong MD. Intimate relationships with their neighbors: tales of stem cells in Drosophila reproductive systems. Dev Dyn. 2005;232:775–790
  317. Gonzalez-Reyes A. Stem cells, niches and cadherins: a view from Drosophila. J Cell Sci. 2003;116:949–954
  318. Song X, Xie T. DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary. Proc Natl Acad Sci USA. 2002;99:14813–14818
  319. Song X, Zhu CH, Doan C, et al. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science. 2002;296:1855–1857
  320. Xie T, Spradling AC. A niche maintaining germ line stem cells in the Drosophila ovary. Science. 2000;290:328–330
  321. Xie T, Spradling AC. Decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell. 1998;94:251–260
  322. Zhu CH, Xie T. Clonal expansion of ovarian germline stem cells during niche formation in Drosophila. Development. 2003;130:2579–2588
  323. Kim KM, Shibata D. Methylation reveals a niche: stem cell succession in human colon crypts. Oncogene. 2002;21:5441–5449
  324. Ward J. Complexity of damage produced by ionizing radiation. Cold Spring Harb Symp Quant Biol. 2000;65:377–382
  325. Chien KR. Stem cells: lost in translation. Nature. 2004;428:607–608
  326. Cheng W, Li B, Kajstura J, et al. Stretch-induced programmed myocyte cell death. J Clin Invest. 1995;96:2247–2259
  327. Leri A, Claudio PP, Li Q, et al. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local RAS and decreases the Bcl-2 to Bax protein ratio in the cell. J Clin Invest. 1998;101:1326–1342
  328. Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol. 1997;59:551–571
  329. Braun KM, Niemann C, Jensen UB, et al. Manipulation of stem cell proliferation and lineage commitment: visualization of label-retaining cells in whole-mounts of mouse epidermis. Development. 2003;130:5241–5255
  330. Shinohara T, Orwig KE, Avarbock MR, et al. Remodeling of the postnatal mouse testis is accompanied by dramatic changes in stem cell number and niche accessibility. Proc Natl Acad Sci USA. 2001;98:6186–6191
  331. Potten CS, Booth C, Tudor GL, et al. Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation. 2003;71:28–41
  332. Yoshimoto M, Shinohara T, Heike T, et al. Direct visualization of transplanted hematopoietic cell reconstruction in intact mouse organs indicates the presence of a niche. Exp Hematol. 2003;31:733–740
  333. Doetsch F. A niche for adult neural stem cells. Curr Opin Genet Dev. 2003;13:543–550
  334. Goldberg GS, Valiunas V, Brink PR. Selective permeability of gap junction channels. Biochim Biophys Acta. 2004;23:96–101
  335. Montecino-Rodriguez E, Dorshkind K. Regulation of hematopoiesis by gap junction-mediated intercellular communication. J Leukoc Biol. 2001;70:341–347
  336. Paraguassu-Braga FH, Borojevic R, Bouzas LF, et al. Bone marrow stroma inhibits proliferation and apoptosis in leukemic cells through gap junction-mediated cell communication. Cell Death Differ. 2003;10:1101–1108
  337. Ryu JK, Choi HB, Hatori K, et al. Adenosine triphosphate induces proliferation of human neural stem cells: role of calcium and p70 ribosomal protein S6 kinase. J Neurosci Res. 2003;72:352–362
  338. Rizzi R, Arcarese ML, Esposito G, et al. Intracellular calcium cycling mediates proliferation and differentiation of human cardiac stem cells. (abst) Circulation. 2007;116:II-203
  339. Kubo H, Berretta RM, MacDonnell S, et al. Ca2+ influx through T-type Ca2+ channels is necessary for differentiation of cardiac stem cells into functional cardiac myocytes. (abst) Circulation. 2007;116:II-225
  340. Yap AS, Kovacs EM. Direct cadherin-activated cell signaling: a view from the plasma membrane. J Cell Biol. 2003;160:11–16
  341. Perez-Moreno M, Jamora C, Fuchs E. Sticky business: orchestrating cellular signals at adherens junctions. Cell. 2003;112:535–548
  342. Jalali S, del Pozo MA, Chen KD, et al. Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc Natl Acad Sci USA. 2001;98:1042–1046
  343. Anversa P, Kajstura J, Leri A, Bolli R. Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation. 2006;113:1451–1463
  344. Anversa P, Leri A, Kajstura J. Cardiac regeneration. J Am Coll Cardiol. 2006;47:1769–1776
  345. Leri A, Kajstura J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev. 2005;85:1373–1416
  346. Bearzi C, Cascapera S, Nascimbene A, et al. Characterization and growth of human cardiac stem cells (Late-breaking developments in stem cell biology and cardiac growth regulation). Circulation. 2005;111:1720
  347. Sarjeant JM, Butany J, Cusimano RJ. Cancer of the heart: epidemiology and management of primary tumors and metastases. Am J Cardiovasc Drugs. 2003;3:407–421
  348. Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation. 2004;109:1615–1622
  349. Olivetti G, Cigola E, Maestri R, et al. Aging, cardiac hypertrophy and ischemic cardiomyopathy do not affect the proportion of mononucleated and multinucleated myocytes in the human heart. J Mol Cell Cardiol. 1996;128:1463–1477
  350. Olivetti G, Melissari M, Balbi T, et al. Myocyte cellular hypertrophy is responsible for ventricular remodeling in the hypertrophied heart of middle aged individuals in the absence of cardiac failure. Cardiovasc Res. 1994;28:1199–1208
  351. Olivetti G, Melissari M, Balbi T, et al. Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans. J Am Coll Cardiol. 1994;24:140–149
  352. Anversa P, Urbanek K, Bearzi C, et al. Cardiac stem cells and the failing heart. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 201–210
  353. Kajstura J, LeCapitaine N, Loredo M, et al. Cardiac stem cells and diabetic cardio-myopathy. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 161–169
  354. Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348:2007–2018
  355. Liew CC, Dzau VJ. Molecular genetics and genomics of heart failure. Nat Rev Genet. 2004;5:811–825
  356. Weber KT. Aldosterone in congestive heart failure. N Engl J Med. 2001;345:1689–1697
  357. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure—abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004;350:1953–1959
  358. Olivetti G, Capasso JM, Meggs LG, et al. Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. Circ Res. 1991;68:856–869
  359. Olivetti G, Ricci R, Anversa P. Hyperplasia of myocyte nuclei in long-term cardiac hypertrophy in rats. J Clin Invest. 1987;80:1818–1821
  360. Olivetti G, Ricci R, Lagrasta C, et al. Cellular basis of wall remodeling in long-term pressure overload-induced right ventricular hypertrophy in rats. Circ Res. 1988;63:648–657
  361. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction (Experimental observations and clinical implications). Circulation. 1990;81:1161–1172
  362. Frustaci A, Kajstura J, Chimenti C, et al. Myocardial cell death in human diabetes. Circ Res. 2000;87:1123–1132
  363. Guerra S, Leri A, Wang X, et al. Myocyte death in the failing human heart is gender dependent. Circ Res. 1999;85:856–866
  364. Olivetti G, Abbi R, Quaini F, et al. Apoptosis in the failing human heart. N Engl J Med. 1997;336:1131–1141
  365. Olivetti G, Quaini F, Sala R, et al. Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart. J Mol Cell Cardiol. 1996;28:2005–2016
  366. Page DL, Caulfield JB, Kastor JA, et al. Myocardial changes associated with cardiogenic shock. N Engl J Med. 1971;285:133–137
  367. Pfeffer MA, Pfeffer JM, Steinberg C, et al. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation. 1985;72:406–412
  368. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling (Behalf of an International Forum on Cardiac Remodeling). J Am Coll Cardiol. 2000;35:569–582
  369. Grossman W, Carbello BA, Gunther S, et al. Ventricular wall stress and the development of cardiac hypertrophy and failure. In: Myocardial Hypertrophy and Failure. New York: Raven; 1983;p. 1–8
  370. Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975;56:56–64
  371. Bache RJ. Effects of hypertrophy on the coronary circulation. Prog Cardiovasc Dis. 1988;30:403–440
  372. Karam R, Healy BP, Wicker P. Coronary reserve is depressed in postmyocardial infarction reactive cardiac hypertrophy. Circulation. 1990;81:238–246
  373. Kajstura J, Cheng W, Sarangarajan R, et al. Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats. Am J Physiol Heart Circ Physiol. 1996;271:H1215–H1228
  374. Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest. 2005;115:572–583
  375. Anversa P, Ricci R, Olivetti G. Effects of exercise on the capillary vasculature of the rat heart. Circulation. 1987;75:I12–I18
  376. Misao Y, Davis ME, Segers VE, et al. Cardiac progenitor cells and biotinylated IGF-l nanofibers improve endogenous and exogenous myocardial regeneration after infarction. (abst) Circulation. 2007;116:II-203
  377. Fiordaliso F, Leri A, Cesselli D, et al. Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death. Diabetes. 2001;50:2363–2375
  378. Bolli R, Anversa P. Stem cells and cardiac aging. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 171–181
  379. Leri A, Liu Y, Li B, et al. Up-regulation of AT(1) and AT(2) receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death. Am J Pathol. 2000;156:1663–1672
  380. Liu Y, Leri A, Li B, et al. Angiotensin II stimulation in vitro induces hypertrophy of normal and postinfarcted ventricular myocytes. Circ Res. 1998;82:1145–1159
  381. Sadoshima J, Qiu Z, Morgan JP, et al. Angiotensin II and other hypertrophic stimuli mediated by G protein-coupled receptors activate tyrosine kinase, mitogen-activated protein kinase, and 90-kD S6 kinase in cardiac myocytes (The critical role of Ca(2+)-dependent signaling). Circ Res. 1995;76:1–15
  382. Sadoshima J, Malhotra R, Izumo S. The role of the cardiac renin-angiotensin system in load-induced cardiac hypertrophy. J Card Fail. 1996;2:S1–S6
  383. Schunkert H, Sadoshima J, Cornelius T, et al. Angiotensin II-induced growth responses in isolated adult rat hearts (Evidence for load-independent induction of cardiac protein synthesis by angiotensin II). Circ Res. 1995;76:489–497
  384. Gonzalez A, Rota M, Nurzynska D, et al. Cardiac progenitor cell aging is responsible for organ aging. (abst) Circulation. 2007;116:II-132
  385. Gonzalez A, Rota M, Nurzynska D, et al. The failing senescent heart contains a pool of functionally competent progenitor cells. (abst) Circulation. 2007;116:II-70
  386. Olivetti G, Giordano G, Corradi D, et al. Gender differences and aging: effects on the human heart. J Am Coll Cardiol. 1995;26:1068–1079
  387. Olivetti G, Melissari M, Capasso JM, et al. Cardiomyopathy of the aging human heart (Myocyte loss and reactive cellular hypertrophy). Circ Res. 1991;68:1560–1568
  388. Camper-Kirby D, Welch S, Walker A, et al. Myocardial Akt activation and gender: increased nuclear activity in females versus males. Circ Res. 2001;88:1020–1027
  389. Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol. 2000;1:72–76
  390. Sherr CJ, DePinho RA. Cellular senescence: mitotic clock or culture shock?. Cell. 2000;102:407–410
  391. Smith RR, Barile L, Cho HC, et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115:896–908
  392. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises (Part I: aging arteries: a “set up” for vascular disease). Circulation. 2003;107:139–146
  393. Narmoneva DA, Vukmirovic R, Davis ME, et al. Endothelial cells promote cardiac myocyte survival and spatial reorganization: implications for cardiac regeneration. Circulation. 2004;110:962–968
  394. Segers VFM, Lee RT. Bioengineered scaffolds: myocytes, endothelial cells and cardiac repair. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 183–191
  395. Simpson D, Liu H, Fan TH, et al. A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling. Stem Cells. 2007;25:2350–2357
  396. Takano H, Komuro I. Cytokines and heart remodeling. In:  Leri A,  Anversa P,  Frishman WH editor. Cardiovascular Regeneration and Stem Cell Therapy. Oxford, UK: Blackwell/Futura; 2007;p. 139–147
  397. Pfeffer MA, Lamas GA, Vaughan DE, et al. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988;319:80–86
  398. Pfeffer JM, Pfeffer MA, Braunwald E. Influence of chronic captopril on the infarcted left ventricle of the rat. Circ Res. 1985;57:84–95
  399. Udelson JE, Patten RD, Konstam MA. New concepts in post-infarction ventricular remodeling. Rev Cardiovasc Med. 2003;4(suppl 3):S3–S12
  400. Taylor MR, Bristow MR. The emerging pharmacogenomics of the beta-adrenergic receptors. Congest Heart Fail. 2004;10:281–288
  401. Frishman WH. Carvedilol. N Engl J Med. 1998;339:1759–1765

 Funded research work from the National Institutes of Health.

 The authors have no conflicts of interest to disclose.

PII: S0146-2806(07)00143-0

doi: 10.1016/j.cpcardiol.2007.11.002

Current Problems in Cardiology
Volume 33, Issue 3 , Pages 91-153 , March 2008

Article Tools

* Image Usage & Resolution