Stem Cell Therapy for Heart Failure Using Cord Blood

  • Amit N. Patel
  • Ramasamy Sakthivel
  • Thomas E. Ichim


Patients with congestive heart failure (CHF) who are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells have been used clinically since 2001. To date, over 1,000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important steps in the field is optimizing treatment approaches. In this chapter, we discuss three main approaches to optimize stem cell therapy efficacy including: (a) increasing stem cell migration to the heart; (b) optimizing stem cell activity; and (c) combining existing stem cell therapies to recapitulate a “therapeutic niche” and the potential of cord blood in cardiovascular regenerative medicine.


Stem Cell Mesenchymal Stem Cell Hepatocyte Growth Factor Umbilical Cord Blood Endothelial Progenitor Cell 
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.


  1. 1.
    Sanchez-Lazaro IJ, Almenar L, Reganon E, et al. Inflammatory markers in stable heart failure and their relationship with functional class. Int J Cardiol. 2007;129(3):388-393.PubMedCrossRefGoogle Scholar
  2. 2.
    Alonso-Martinez JL, Llorente-Diez B, Echegaray-Agara M, Olaz-Preciado F, Urbieta-Echezarreta M, Gonzalez-Arencibia C. C-reactive protein as a predictor of improvement and readmission in heart failure. Eur J Heart Fail. 2002;4:331-336.PubMedCrossRefGoogle Scholar
  3. 3.
    Nakou ES, Liberopoulos EN, Milionis HJ, Elisaf MS. The role of C-reactive protein in atherosclerotic cardiovascular disease: an overview. Curr Vasc Pharmacol. 2008;6:258-270.PubMedCrossRefGoogle Scholar
  4. 4.
    Galarraga B, Khan F, Kumar P, Pullar T, Belch JJ. C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis. Rheumatology (Oxford). 2008;47(12):1780-1784.CrossRefGoogle Scholar
  5. 5.
    Nabata A, Kuroki M, Ueba H, et al. C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: Implications for the destabilization of atherosclerotic plaque. Athero­sclerosis. 2008;196:129-135.PubMedCrossRefGoogle Scholar
  6. 6.
    Griselli M, Herbert J, Hutchinson WL, et al. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med. 1999;190:1733-1740.PubMedCrossRefGoogle Scholar
  7. 7.
    Pepys MB, Hirschfield GM, Tennent GA, et al. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006;440:1217-1221.PubMedCrossRefGoogle Scholar
  8. 8.
    Satoh M, Minami Y, Takahashi Y, Nakamura M. Immune modulation: role of the inflammatory cytokine cascade in the failing human heart. Curr Heart Fail Rep. 2008;5:69-74.PubMedCrossRefGoogle Scholar
  9. 9.
    Yokoyama T, Sekiguchi K, Tanaka T, et al. Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts. Am J Physiol. 1999;276:H1968-H1976.PubMedGoogle Scholar
  10. 10.
    Wang BW, Hung HF, Chang H, Kuan P, Shyu KG. Mechanical stretch enhances the expression of resistin gene in cultured cardiomyocytes via tumor necrosis factor-alpha. Am J Physiol Heart Circ Physiol. 2007;293:H2305-H2312.PubMedCrossRefGoogle Scholar
  11. 11.
    Satoh S, Oyama J, Suematsu N, et al. Increased productivity of tumor necrosis factor-alpha in helper T cells in patients with systolic heart failure. Int J Cardiol. 2006;111:405-412.PubMedCrossRefGoogle Scholar
  12. 12.
    Conraads VM, Bosmans JM, Schuerwegh AJ, et al. Intracellular monocyte cytokine production and CD 14 expression are up-regulated in severe vs mild chronic heart failure. J Heart Lung Transplant. 2005;24:854-859.PubMedCrossRefGoogle Scholar
  13. 13.
    Haudek SB, Taffet GE, Schneider MD, Mann DL. TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. J Clin Invest. 2007;117:2692-2701.PubMedCrossRefGoogle Scholar
  14. 14.
    Kubota T, Bounoutas GS, Miyagishima M, et al. Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy. Circulation. 2000;101:2518-2525.PubMedGoogle Scholar
  15. 15.
    Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol. 2006;177:1272-1281.PubMedGoogle Scholar
  16. 16.
    Termeer C, Benedix F, Sleeman J, et al. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med. 2002;195:99-111.PubMedCrossRefGoogle Scholar
  17. 17.
    Asea A. Heat shock proteins and toll-like receptors. Handb Exp Pharmacol. 2008;183:111-127.PubMedCrossRefGoogle Scholar
  18. 18.
    Nozaki N, Shishido T, Takeishi Y, Kubota I. Modulation of doxorubicin-induced cardiac dysfunction in toll-like receptor-2-knockout mice. Circulation. 2004;110:2869-2874.PubMedCrossRefGoogle Scholar
  19. 19.
    Riad A, Bien S, Gratz M, et al. Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice. Eur J Heart Fail. 2008;10:233-243.PubMedCrossRefGoogle Scholar
  20. 20.
    Shishido T, Nozaki N, Yamaguchi S, et al. Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction. Circulation. 2003;108:2905-2910.PubMedCrossRefGoogle Scholar
  21. 21.
    Sheu JJ, Chang LT, Chiang CH, et al. Prognostic value of activated toll-like receptor-4 in monocytes following acute myocardial infarction. Int Heart J. 2008;49:1-11.PubMedCrossRefGoogle Scholar
  22. 22.
    Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6:230-247.PubMedCrossRefGoogle Scholar
  23. 23.
    Zannettino AC, Paton S, Arthur A, et al. Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol. 2008;214:413-421.PubMedCrossRefGoogle Scholar
  24. 24.
    Hoogduijn MJ, Crop MJ, Peeters AM, et al. Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev. 2007;16:597-604.PubMedCrossRefGoogle Scholar
  25. 25.
    Chao KC, Chao KF, Fu YS, Liu SH. Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS ONE. 2008;3:e1451.PubMedCrossRefGoogle Scholar
  26. 26.
    Jo YY, Lee HJ, Kook SY, et al. Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng. 2007;13:767-773.PubMedCrossRefGoogle Scholar
  27. 27.
    He Q, Wan C, Li G. Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells. 2007;25:69-77.PubMedCrossRefGoogle Scholar
  28. 28.
    Oh W, Kim DS, Yang YS, Lee JK. Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cell Immunol. 2008;251(2):116-123.PubMedCrossRefGoogle Scholar
  29. 29.
    Meng X, Ichim TE, Zhong J, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med. 2007;5:57.PubMedCrossRefGoogle Scholar
  30. 30.
    Hida N, Nishiyama N, Miyoshi S, et al. Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem Cells. 2008;26(7):1695-1704.PubMedCrossRefGoogle Scholar
  31. 31.
    Patel AN, Park E, Kuzman M, Benetti F, Silva FJ, Allickson JG. Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transplant. 2008;17:303-311.PubMedCrossRefGoogle Scholar
  32. 32.
    Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007;262:509-525.PubMedCrossRefGoogle Scholar
  33. 33.
    Keyser KA, Beagles KE, Kiem HP. Comparison of mesenchymal stem cells from different tissues to suppress T-cell activation. Cell Transplant. 2007;16:555-562.PubMedGoogle Scholar
  34. 34.
    Nasef A, Chapel A, Mazurier C, et al. Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells. Gene Expr. 2007;13:217-226.PubMedCrossRefGoogle Scholar
  35. 35.
    Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007;149:353-363.PubMedCrossRefGoogle Scholar
  36. 36.
    Nasef A, Mazurier C, Bouchet S, et al. Leukemia inhibitory factor: role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol. 2008;253:16-22.PubMedCrossRefGoogle Scholar
  37. 37.
    Selmani Z, Naji A, Zidi I, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4 + CD25highFOXP3+ regulatory T cells. Stem Cells. 2008;26:212-222.PubMedCrossRefGoogle Scholar
  38. 38.
    Ortiz LA, Dutreil M, Fattman C, et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA. 2007;104:11002-11007.PubMedCrossRefGoogle Scholar
  39. 39.
    English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol Lett. 2007;110:91-100.PubMedCrossRefGoogle Scholar
  40. 40.
    Jones BJ, Brooke G, Atkinson K, McTaggart SJ. Immunosuppression by placental indoleamine 2, 3-dioxygenase: a role for mesenchymal stem cells. Placenta. 2007;28:1174-1181.PubMedCrossRefGoogle Scholar
  41. 41.
    Casiraghi F, Azzollini N, Cassis P, et al. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. J Immunol. 2008;181:3933-3946.PubMedGoogle Scholar
  42. 42.
    Kassis I, Grigoriadis N, Gowda-Kurkalli B, et al. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol. 2008;65:753-761.PubMedCrossRefGoogle Scholar
  43. 43.
    Parekkadan B, Tilles AW, Yarmush ML. Bone marrow-derived mesenchymal stem cells ameliorate autoimmune enteropathy independently of regulatory T cells. Stem Cells. 2008;26:1913-1919.PubMedCrossRefGoogle Scholar
  44. 44.
    Li H, Guo Z, Jiang X, Zhu H, Li X, Mao N. Mesenchymal stem cells alter migratory property of T and dendritic cells to delay the development of murine lethal acute graft-versus-host disease. Stem Cells. 2008;26(10):2531-2541.PubMedCrossRefGoogle Scholar
  45. 45.
    Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G. Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum. 2007;56:1175-1186.PubMedCrossRefGoogle Scholar
  46. 46.
    Semedo P, Wang PM, Andreucci TH, et al. Mesenchymal stem cells ameliorate tissue damages triggered by renal ischemia and reperfusion injury. Transplant Proc. 2007;39:421-423.PubMedCrossRefGoogle Scholar
  47. 47.
    Du YY, Zhou SH, Zhou T, et al. Immuno-inflammatory regulation effect of mesenchymal stem cell transplantation in a rat model of myocardial infarction. Cytotherapy. 2008;10:469-478.PubMedCrossRefGoogle Scholar
  48. 48.
    Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579-1586.PubMedCrossRefGoogle Scholar
  49. 49.
    Ning H, Yang F, Jiang M, et al. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia. 2008;22:593-599.PubMedCrossRefGoogle Scholar
  50. 50.
    Ball L, Bredius R, Lankester A, et al. Third party mesenchymal stromal cell infusions fail to induce tissue repair despite successful control of severe grade IV acute graft-versus-host disease in a child with juvenile myelo-monocytic leukemia. Leukemia. 2008;22:1256-1257.PubMedCrossRefGoogle Scholar
  51. 51.
    Ringden O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006;81:1390-1397.PubMedCrossRefGoogle Scholar
  52. 52.
    Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439-1441.PubMedCrossRefGoogle Scholar
  53. 53.
    Muller I, Kordowich S, Holzwarth C, et al. Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis. 2008;40:25-32.PubMedCrossRefGoogle Scholar
  54. 54.
    Narula J, Haider N, Virmani R, et al. Apoptosis in myocytes in end-stage heart failure. N Engl J Med. 1996;335:1182-1189.PubMedCrossRefGoogle Scholar
  55. 55.
    Dorn GW 2nd. Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling. Cardiovasc Res. 2008;81(3):465-473.PubMedCrossRefGoogle Scholar
  56. 56.
    Rodriguez M, Lucchesi BR, Schaper J. Apoptosis in myocardial infarction. Ann Med. 2002;34:470-479.PubMedCrossRefGoogle Scholar
  57. 57.
    Odashima M, Usui S, Takagi H, et al. Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction. Circ Res. 2007;100:1344-1352.PubMedCrossRefGoogle Scholar
  58. 58.
    Chua CC, Gao J, Ho YS, et al. Overexpression of IAP-2 attenuates apoptosis and protects against myocardial ischemia/reperfusion injury in transgenic mice. Biochim Biophys Acta. 2007;1773:577-583.PubMedCrossRefGoogle Scholar
  59. 59.
    Jayasankar V, Woo YJ, Bish LT, et al. Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure. Circulation. 2003;108(suppl 1):II230-II236.PubMedGoogle Scholar
  60. 60.
    Filippatos G, Uhal BD. Blockade of apoptosis by ACE inhibitors and angiotensin receptor antagonists. Curr Pharm Des. 2003;9:707-714.PubMedCrossRefGoogle Scholar
  61. 61.
    Fransioli J, Bailey B, Gude NA, et al. Evolution of the c-kit-positive cell response to pathological challenge in the myocardium. Stem Cells. 2008;26:1315-1324.PubMedCrossRefGoogle Scholar
  62. 62.
    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. 2005;102:8692-8697.PubMedCrossRefGoogle Scholar
  63. 63.
    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.PubMedCrossRefGoogle Scholar
  64. 64.
    Raffaghello L, Bianchi G, Bertolotto M, et al. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells. 2008;26:151-162.PubMedCrossRefGoogle Scholar
  65. 65.
    Mirotsou M, Zhang Z, Deb A, et al. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci USA. 2007;104:1643-1648.PubMedCrossRefGoogle Scholar
  66. 66.
    Wang M, Crisostomo PR, Herring C, Meldrum KK, Meldrum DR. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006;291:R880-R884.PubMedGoogle Scholar
  67. 67.
    Li TS, Takahashi M, Ohshima M, et al. Myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells. Cell Transplant. 2008;17:695-703.PubMedCrossRefGoogle Scholar
  68. 68.
    Crisostomo PR, Wang Y, Markel TA, Wang M, Lahm T, Meldrum DR. Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. Am J Physiol Cell Physiol. 2008;294:C675-C682.PubMedCrossRefGoogle Scholar
  69. 69.
    Fu X, He Y, Xie C, Liu W. Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy. 2008;10:353-363.PubMedCrossRefGoogle Scholar
  70. 70.
    Urbanek K, Rota M, Cascapera S, et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res. 2005;97:663-673.PubMedCrossRefGoogle Scholar
  71. 71.
    Zeng F, Chen MJ, Baldwin DA, et al. Multiorgan engraftment and differentiation of human cord blood CD34+ Lin-cells in goats assessed by gene expression profiling. Proc Natl Acad Sci USA. 2006;103:7801-7806.PubMedCrossRefGoogle Scholar
  72. 72.
    Nishiyama N, Miyoshi S, Hida N, et al. The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro. Stem Cells. 2007;25:2017-2024.PubMedCrossRefGoogle Scholar
  73. 73.
    Kawada H, Fujita J, Kinjo K, et al. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood. 2004;104:3581-3587.PubMedCrossRefGoogle Scholar
  74. 74.
    Vieyra DS, Jackson KA, Goodell MA. Plasticity and tissue regenerative potential of bone marrow-derived cells. Stem Cell Rev. 2005;1:65-69.PubMedCrossRefGoogle Scholar
  75. 75.
    Fazel S, Cimini M, Chen L, et al. Cardioprotective c-kit + cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest. 2006;116:1865-1877.PubMedCrossRefGoogle Scholar
  76. 76.
    Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7:430-436.PubMedCrossRefGoogle Scholar
  77. 77.
    Li RK, Jia ZQ, Weisel RD, et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg. 1996;62:654-661.PubMedCrossRefGoogle Scholar
  78. 78.
    El Oakley RM, Ooi OC, Bongso A, Yacoub MH. Myocyte transplantation for myocardial repair: a few good cells can mend a broken heart. Ann Thorac Surg. 2001;71:1724-1733.PubMedCrossRefGoogle Scholar
  79. 79.
    Klug MG, Soonapaa MH, Koh GY, Field LJ. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest. 1996;98:216-224.PubMedCrossRefGoogle Scholar
  80. 80.
    Tomita S, Li RK, Weisel RD, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation. 1999;100:II247-II256.PubMedGoogle Scholar
  81. 81.
    Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998;4:929-933.PubMedCrossRefGoogle Scholar
  82. 82.
    Dib N, McCarthy P, Campbell A, et al. Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplant. 2005;14:1-9.CrossRefGoogle Scholar
  83. 83.
    Dib N, Michler RE, Pagani FD, et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation. 2005;112:1748-1755.PubMedCrossRefGoogle Scholar
  84. 84.
    Dimarakis I, Habib NA, Gordon MYA. Adult bone marrow-derived stem cells and the injured heart: just the beginning? Eur J Cardiothorac Surg. 2005;28:665-676.PubMedCrossRefGoogle Scholar
  85. 85.
    Dec GW. Management of heart failure: crossing boundary over to the surgical country. Surg Clin North Am. 2004;84:1-25.PubMedCrossRefGoogle Scholar
  86. 86.
    Erbs S, Linke A, Adams V, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Cir Res. 2005;97:756-762.CrossRefGoogle Scholar
  87. 87.
    Evers BM, Weissman IL, Flake AW, Tabar V, Weisel RD. Stem cells in clinical practice. J Am Coll Surg. 2003;197:458-478.PubMedCrossRefGoogle Scholar
  88. 88.
    Forrester JS, Price MJ, Makkar RR. Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation. 2003;108:1139-1145.PubMedCrossRefGoogle Scholar
  89. 89.
    Soonpaa MH, Koh GY, Klug MG, Field LJ. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science. 1994;264:98-101.PubMedCrossRefGoogle Scholar
  90. 90.
    Scorsin M, Marotte F, Sabri A, et al. Can grafted cardiomyocytes colonize periinfarction myocardial areas? Circulation. 1996;94:337-340.Google Scholar
  91. 91.
    Li RK, Mickle D, Weisel RD, et al. In vivo survival and function of transplanted rat cardiomyocytes. Cir Res. 1996;78:283-288.Google Scholar
  92. 92.
    Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg. 1995;60:12-18.PubMedGoogle Scholar
  93. 93.
    Murry CE, Wiseman RW, Schwartz SM, Hauschka SD. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest. 1996;98:2512-2523.PubMedCrossRefGoogle Scholar
  94. 94.
    Scorsin M, Hagege A, Vilguin J-T, et al. Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg. 2000;119:1169-1175.PubMedCrossRefGoogle Scholar
  95. 95.
    Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998;4:929-933.PubMedCrossRefGoogle Scholar
  96. 96.
    Atkins BZ, Lewis CW, Kraus WE, et al. Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ. Ann Thorac Surg. 1999;67:124-129.PubMedCrossRefGoogle Scholar
  97. 97.
    Menasché P, Hagege AA, Scorsin M, et al. Myoblast transplantation for heart failure. Lancet. 2001;357:279-280.PubMedCrossRefGoogle Scholar
  98. 98.
    Siminiak T, Kalawski R, Kurpisz M. Myoblast transplantation in the treatment of postinfarction myocardial contractility impairment. Kardiol Pol. 2002;56:131-137.Google Scholar
  99. 99.
    Herreros J, Prósper F, Perey A, et al. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J. 2003;24:2012.PubMedCrossRefGoogle Scholar
  100. 100.
    Bittner RE, Schofer C, Weipoltshammer K, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl). 1999;199:391-396.CrossRefGoogle Scholar
  101. 101.
    Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797-1806.PubMedCrossRefGoogle Scholar
  102. 102.
    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;7:1028-1304.PubMedCrossRefGoogle Scholar
  103. 103.
    Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001;107:1395-1402.PubMedCrossRefGoogle Scholar
  104. 104.
    Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105:93-98.PubMedCrossRefGoogle Scholar
  105. 105.
    Nishikawa S. A complex linkage in the developmental pathway of endothelial and hematopoietic. Curr Opin Cell. 2001;13:673-678.CrossRefGoogle Scholar
  106. 106.
    Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002;109:337-346.PubMedGoogle Scholar
  107. 107.
    Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK. 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.PubMedGoogle Scholar
  108. 108.
    Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW. Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation. 2004;109:3154-3157.PubMedCrossRefGoogle Scholar
  109. 109.
    Strauer BE, Brehm M, Zeus T, et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr. 2001;126:932-938.PubMedCrossRefGoogle Scholar
  110. 110.
    Hamano K, Nishida M, Hirata K, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001;65:845-847.PubMedCrossRefGoogle Scholar
  111. 111.
    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.PubMedCrossRefGoogle Scholar
  112. 112.
    Martin-Rendon E, Brunskill S, Doree C, Hyde C, Watt S, Mathur A, Stanworth, S. Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev. 2008;(4):CD006536.Google Scholar
  113. 113.
    Kang S, Yang YJ, Li CJ, Gao RL. Effects of intracoronary autologous bone marrow cells on left ventricular function in acute myocardial infarction: a systematic review and meta-analysis for randomized controlled trials. Coron Artery Dis. 2008;19:327-335.PubMedCrossRefGoogle Scholar
  114. 114.
    Cheng Z, Ou L, Zhou X, et al. Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther. 2008;16:571-579.PubMedCrossRefGoogle Scholar
  115. 115.
    Murry CE et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;429:664-668.CrossRefGoogle Scholar
  116. 116.
    Balsam LB et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature. 2004;428:668-673.PubMedCrossRefGoogle Scholar
  117. 117.
    Assmus B, Schachinger V, Teupe C, et al. Transplantation of cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002;106:3009-3017.PubMedCrossRefGoogle Scholar
  118. 118.
    Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106:1913-1918.PubMedCrossRefGoogle Scholar
  119. 119.
    Stamm C, Westphal B, Kleine HD. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361:45-46.PubMedCrossRefGoogle Scholar
  120. 120.
    Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000;95:3106-3112.PubMedGoogle Scholar
  121. 121.
    Stamm C et al. CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg. 2004;52:152-158.PubMedCrossRefGoogle Scholar
  122. 122.
    Bartunek J, Vanderheyden M, Vandekerckhove B, et al. Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation. 2005;112:178-183.Google Scholar
  123. 123.
    Pierelli L, Bonanno G, Rutella S, Marone M, Scambia G, Leone G. CD105 (endoglin) expression on hematopoietic stem/progenitor cells. Leuk Lymphoma. 2001;42:1195-1206.PubMedCrossRefGoogle Scholar
  124. 124.
    Barry FP, Boynton R, Haynesworth S, Murphy JM, Zaia J. The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105). Biochem Biophys Res Commun. 1999;265:134-139.PubMedCrossRefGoogle Scholar
  125. 125.
    Cheng T, Scadden D. Cell cycle entry of hematopoietic stem and progenitor cells controlled by distinct cyclin-dependent kinase inhibitors. Int J Hematol. 2002;75:460-465.PubMedCrossRefGoogle Scholar
  126. 126.
    Wang Z, Miura N, Bonelli A, et al. Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. Blood. 2002;99:2740-2747.PubMedCrossRefGoogle Scholar
  127. 127.
    Herrera MB, Bussolati B, Bruno S, et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int. 2007;72:430-441.PubMedCrossRefGoogle Scholar
  128. 128.
    Sackstein R, Merzaban JS, Cain DW, et al. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med. 2008;14:181-187.PubMedCrossRefGoogle Scholar
  129. 129.
    Zhu H, Mitsuhashi N, Klein A, et al. The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells. 2006;24:928-935.PubMedCrossRefGoogle Scholar
  130. 130.
    Wang Y, Deng Y, Zhou GQ. SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res. 2008;1195:104-112.PubMedCrossRefGoogle Scholar
  131. 131.
    Neschadim A, McCart JA, Keating A, Medin JA. A roadmap to safe, efficient, and stable lentivirus-mediated gene therapy with hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2007;13:1407-1416.PubMedCrossRefGoogle Scholar
  132. 132.
    Hung SC, Pochampally RR, Hsu SC, et al. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS ONE. 2007;2:e416.PubMedCrossRefGoogle Scholar
  133. 133.
    Shi M, Li J, Liao L, et al. Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica. 2007;92:897-904.PubMedCrossRefGoogle Scholar
  134. 134.
    Tang YL, Qian K, Zhang YC, Shen L, Phillips MI. Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regul Pept. 2005;125:1-8.PubMedCrossRefGoogle Scholar
  135. 135.
    Gibble JW, Ness PM. Fibrin glue: the perfect operative sealant? Transfusion. 1990;30:741-747.PubMedCrossRefGoogle Scholar
  136. 136.
    Zhang G, Nakamura Y, Wang X, Hu Q, Suggs LJ, Zhang J. Controlled release of stromal cell-derived factor-1 alpha in situ increases c-kit + cell homing to the infarcted heart. Tissue Eng. 2007;13:2063-2071.PubMedCrossRefGoogle Scholar
  137. 137.
    Barile L, Messina E, Giacomello A, Marban E. Endogenous cardiac stem cells. Prog Cardiovasc Dis. 2007;50:31-48.PubMedCrossRefGoogle Scholar
  138. 138.
    Tan Y, Shao H, Eton D, et al. Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor. Cardiovasc Res. 2007;73:823-832.PubMedCrossRefGoogle Scholar
  139. 139.
    Latini R, Brines M, Fiordaliso F. Do non-hemopoietic effects of erythropoietin play a beneficial role in heart failure? Heart Fail Rev. 2008;13:415-423.PubMedCrossRefGoogle Scholar
  140. 140.
    Brunner S, Winogradow J, Huber BC, et al. Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. Faseb J. 2009;23(2):351-361.PubMedCrossRefGoogle Scholar
  141. 141.
    Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA. Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol. 2007;5:e201.PubMedCrossRefGoogle Scholar
  142. 142.
    Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111:2981-2987.PubMedCrossRefGoogle Scholar
  143. 143.
    Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002;297:2256-2259.PubMedCrossRefGoogle Scholar
  144. 144.
    Rose RA, Jiang H, Wang X, et al. Bone marrow-derived mesenchymal stromal cells express cardiac-specific markers, retain the stromal phenotype and do not become functional cardiomyocytes in vitro. Stem Cells. 2008;26(11):2884-2892.PubMedCrossRefGoogle Scholar
  145. 145.
    Makino S, Fukuda K, Miyoshi S, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999;103:697-705.PubMedCrossRefGoogle Scholar
  146. 146.
    De Felice L, Tatarelli C, Mascolo MG, et al. Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res. 2005;65:1505-1513.PubMedCrossRefGoogle Scholar
  147. 147.
    Bug G, Gul H, Schwarz K, et al. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res. 2005;65:2537-2541.PubMedCrossRefGoogle Scholar
  148. 148.
    Lee TM, Lin MS, Chang NC. Inhibition of histone deacetylase on ventricular remodeling in infarcted rats. Am J Physiol Heart Circ Physiol. 2007;293:H968-H977.PubMedCrossRefGoogle Scholar
  149. 149.
    Hattori N, Imao Y, Nishino K, et al. Epigenetic regulation of Nanog gene in embryonic stem and trophoblast stem cells. Genes Cells. 2007;12:387-396.PubMedCrossRefGoogle Scholar
  150. 150.
    Go MJ, Takenaka C, Ohgushi H. Forced expression of Sox2 or Nanog in human bone marrow derived mesenchymal stem cells maintains their expansion and differentiation capabilities. Exp Cell Res. 2008;314:1147-1154.PubMedCrossRefGoogle Scholar
  151. 151.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663-676.PubMedCrossRefGoogle Scholar
  152. 152.
    Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861-872.PubMedCrossRefGoogle Scholar
  153. 153.
    Hanna J, Wernig M, Markoulaki S, et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007;318:1920-1923.PubMedCrossRefGoogle Scholar
  154. 154.
    Kim JB, Zaehres H, Wu G, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature. 2008;454:646-650.PubMedCrossRefGoogle Scholar
  155. 155.
    Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science. 2008;322(5903):949-953.PubMedCrossRefGoogle Scholar
  156. 156.
    Yang S, Lin G, Tan YQ, et al. Tumor progression of culture-adapted human embryonic stem cells during long-term culture. Genes Chromosomes Cancer. 2008;47:665-679.PubMedCrossRefGoogle Scholar
  157. 157.
    Ben-Porath I, Thomson MW, Carey VJ, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008;40:499-507.PubMedCrossRefGoogle Scholar
  158. 158.
    Li L, Baroja ML, Majumdar A, et al. Human embryonic stem cells possess immune-privileged properties. Stem Cells. 2004;22:448-456.PubMedCrossRefGoogle Scholar
  159. 159.
    Slavin S, Kurkalli BG, Karussis D. The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders. Clin Neurol Neurosurg. 2008;110(9):943-946.PubMedCrossRefGoogle Scholar
  160. 160.
    von Bonin M, Stolzel F, Goedecke A, et al. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2008;43(3):245-251.CrossRefGoogle Scholar
  161. 161.
    Dunac A, Frelin C, Popolo-Blondeau M, Chatel M, Mahagne MH, Philip PJ. Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization. J Neurol. 2007;254:327-332.PubMedCrossRefGoogle Scholar
  162. 162.
    Taguchi A, Nakagomi N, Matsuyama T, et al. Circulating CD34-positive cells have prognostic value for neurologic function in patients with past cerebral infarction. J Cereb Blood Flow Metab. 2008;29(1):34-38.PubMedCrossRefGoogle Scholar
  163. 163.
    Grundmann F, Scheid C, Braun D, et al. Differential increase of CD34, KDR/CD34, CD133/CD34 and CD117/CD34 positive cells in peripheral blood of patients with acute myocardial infarction. Clin Res Cardiol. 2007;96:621-627.PubMedCrossRefGoogle Scholar
  164. 164.
    Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med. 2004;14:1035-1041.PubMedGoogle Scholar
  165. 165.
    Seebach C, Henrich D, Tewksbury R, Wilhelm K, Marzi I. Number and proliferative capacity of human mesenchymal stem cells are modulated positively in multiple trauma patients and negatively in atrophic nonunions. Calcif Tissue Int. 2007;80:294-300.PubMedCrossRefGoogle Scholar
  166. 166.
    Ciulla MM, Ferrero S, Gianelli U, Paliotti R, Magrini F, Braidotti P. Direct visualization of neo-vessel formation following peripheral injection of bone marrow derived CD34+ cells in experimental myocardial damage. Micron. 2007;38:321-322.PubMedCrossRefGoogle Scholar
  167. 167.
    Wojakowski W, Tendera M. Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes. Folia Histochem Cytobiol. 2005;43:229-232.PubMedGoogle Scholar
  168. 168.
    Paczkowska E, Larysz B, Rzeuski R, et al. Human hematopoietic stem/progenitor-enriched CD34(+) cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction. Eur J Haematol. 2005;75:461-467.PubMedCrossRefGoogle Scholar
  169. 169.
    Wang XY, Lan Y, He WY, et al. Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood. 2008;111:2436-2443.PubMedCrossRefGoogle Scholar
  170. 170.
    Dexter TM. Stromal cell associated haemopoiesis. J Cell Physiol Suppl. 1982;1:87-94.PubMedCrossRefGoogle Scholar
  171. 171.
    Bakhshi T, Zabriskie RC, Bodie S, et al. Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture. Transfusion. 2008;48(12):2638-2644.PubMedCrossRefGoogle Scholar
  172. 172.
    Huang GP, Pan ZJ, Jia BB, et al. Ex vivo expansion and transplantation of hematopoietic stem/progenitor cells supported by mesenchymal stem cells from human umbilical cord blood. Cell Transplant. 2007;16:579-585.PubMedCrossRefGoogle Scholar
  173. 173.
    Urban VS, Kiss J, Kovacs J, et al. Mesenchymal stem cells cooperate with bone marrow cells in therapy of diabetes. Stem Cells. 2008;26:244-253.PubMedCrossRefGoogle Scholar
  174. 174.
    Ichim TE, Solano F, Brenes R, et al. Placental mesenchymal and cord blood stem cell therapy for dilated cardiomyopathy. Reprod Biomed Online. 2008;16:898-905.PubMedCrossRefGoogle Scholar
  175. 175.
    Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593-600.PubMedCrossRefGoogle Scholar
  176. 176.
    Van Zant G, Liang Y. The role of stem cells in aging. Exp Hematol. 2003;31:659-672.PubMedCrossRefGoogle Scholar
  177. 177.
    Wojakowski W, Tendera M, Michalowska A, et al. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met + stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004;110:3213-3220.PubMedCrossRefGoogle Scholar
  178. 178.
    Locatelli F, Rocha V, Reed W, et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood. 2003;101:2137-2143.PubMedCrossRefGoogle Scholar
  179. 179.
    Cornetta K, Laughlin M, Carter S, et al. Umbilical cord blood transplantation in adults: results of the prospective Cord Blood Transplantation (COBLT). Biol Blood Marrow Transplant. 2005;11:149-160.PubMedCrossRefGoogle Scholar
  180. 180.
    Lubin BH and Shearer WT. Cord blood banking for potential future transplantation. Pediatrics. 2007;119:165-170.Google Scholar
  181. 181.
    Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med. 1997;337:373-381.PubMedCrossRefGoogle Scholar
  182. 182.
    Laughlin MJ, Barker J, Bambach B, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001;344:1815-1822.PubMedCrossRefGoogle Scholar
  183. 183.
    Matsumura T, Narimatsu H, Kami M, et al. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients. Biol Blood Marrow Transplant. 2007;13:577-583.PubMedCrossRefGoogle Scholar
  184. 184.
    Sasazuki T, Juji T, Morishima Y, et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med. 1998;339:1177-1185.PubMedCrossRefGoogle Scholar
  185. 185.
    Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ. Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant. 2002;8:257-260.PubMedCrossRefGoogle Scholar
  186. 186.
    Limbourg F, Ringes-Lichtenberg S, Schaefer A, et al. Haematopoietic stem cells improve cardiac function after infarction without permanent cardiac engraftment. Eur J Heart Fail. 2005;7:722-729.PubMedCrossRefGoogle Scholar
  187. 187.
    Asahara T. Stem cell biology for vascular regeneration. Ernst Schering Res Found Workshop. 2005;54:111-129.PubMedCrossRefGoogle Scholar
  188. 188.
    Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 2003;47:149-161.PubMedGoogle Scholar
  189. 189.
    Brogi E, Wu T, Namiki A, Isner JM. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation. 1994;90:649-652.PubMedGoogle Scholar
  190. 190.
    Nicosia RF, Nicosia SV, Smith M. Vascular endothelial growth factor, platelet-derived growth factor, and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am J Pathol. 1994;145:1023-1029.PubMedGoogle Scholar
  191. 191.
    Bos R, van Diest PJ, de Jong JS, van der Groep P, van der Valk P, van der Wall E. Hypoxia-inducible factor-1alpha is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer. Histopathology. 2005;46:31-36.PubMedCrossRefGoogle Scholar
  192. 192.
    Schlingemann RO. Role of growth factors and the wound healing response in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2004;242:91-101.PubMedCrossRefGoogle Scholar
  193. 193.
    Mentlein R, Held-Feindt J. Angiogenesis factors in gliomas: a new key to tumour therapy? Naturwissenschaften. 2003;90:385-394.PubMedCrossRefGoogle Scholar
  194. 194.
    Zhao L, Eghbali-Webb M. Release of pro- and anti-angiogenic factors by human cardiac fibroblasts: effects on DNA synthesis and protection under hypoxia in human endothelial cells. Biochim Biophys Acta. 2001;1538:273-282.PubMedCrossRefGoogle Scholar
  195. 195.
    Dunn IF, Heese O, Black PM. Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs. J Neurooncol. 2000;50:121-137.PubMedCrossRefGoogle Scholar
  196. 196.
    Kano MR, Morishita Y, Iwata C, et al. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling. J Cell Sci. 2005;118:3759-3768.PubMedCrossRefGoogle Scholar
  197. 197.
    Laschke MW, Elitzsch A, Vollmar B, Vajkoczy P, Menger MD. Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions. Hum Reprod. 2006;21:262-268.PubMedCrossRefGoogle Scholar
  198. 198.
    Kelly BD, Hackett SF, Hirota K, et al. Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res. 2003;93:1074-1081.PubMedCrossRefGoogle Scholar
  199. 199.
    Chauhan AMR, Mullins PA, Taylor G, Petch C, Schofield PM. Aging-associated endothelial dysfunction in humans is reversed by L-arginine. J Am Coll Cardiol. 1996;28:1796-1804.PubMedCrossRefGoogle Scholar
  200. 200.
    Tschudi MR, Barton M, Bersinger NA, et al. Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery. J Clin Invest. 1996;98:899-905.PubMedCrossRefGoogle Scholar
  201. 201.
    Hill JM, Syed MA, Arai AE, et al. Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease. J Am Coll Cardiol. 2005;46:1643-1648.PubMedCrossRefGoogle Scholar
  202. 202.
    Charles A. Goldthwaite, J. Mending a broken heart: stem cells and cardiac repair. In: Regenerative Medicine. Bethesda, MD: (National Institute of Health. Department of Health and Human Services; 2006.Google Scholar
  203. 203.
    Bonanno G, Mariotti A, Procoli A, et al. Human cord blood CD133+ cells immunoselected by a clinical-grade apparatus differentiate in vitro into endothelial- and cardiomyocyte-like cells. Transfusion. 2007;47(2):280-289.PubMedCrossRefGoogle Scholar
  204. 204.
    Cheng F, Zou P, Yang H, et al. Induced differentiation of human cord blood mesenchymal stem/progenitor cells into cardiomyocyte-like cells in vitro. J Huazong Univ Sci Technol Med Sci. 2003;23:154-157.CrossRefGoogle Scholar
  205. 205.
    Yamada Y, Yokoyama S, Fukuda N, et al. A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue. Biochem Biophys Res Commun. 2007;353:182-188.PubMedCrossRefGoogle Scholar

Copyright information

© Springer London 2011

Authors and Affiliations

  • Amit N. Patel
    • 1
  • Ramasamy Sakthivel
  • Thomas E. Ichim
  1. 1.Divison of Cardiothoracic SurgeryDirector of Clinical Regenerative Medicine, CTFSalt Lake CityUSA

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