Skip to main content
Top
Published in: Current Treatment Options in Cardiovascular Medicine 7/2014

Open Access 01-07-2014 | Regenerative Medicine and Stem-cell Therapy (S Wu and P Hsieh, Section Editors)

Cardiac Stem Cell Therapy for Cardiac Repair

Authors: Kyung U. Hong, Ph.D., Roberto Bolli, M.D.

Published in: Current Treatment Options in Cardiovascular Medicine | Issue 7/2014

Login to get access

Opinion statement

The discovery of adult cardiac stem cells (CSCs) and their potential to restore functional cardiac tissue has fueled unprecedented interest in recent years. Indeed, stem-cell–based therapies have the potential to transform the treatment and prognosis of heart failure, for they have the potential to eliminate the underlying cause of the disease by reconstituting the damaged heart with functional cardiac cells. Over the last decade, several independent laboratories have demonstrated the utility of c-kit+/Lin- resident CSCs in alleviating left ventricular dysfunction and remodeling in animal models of acute and chronic myocardial infarction. Recently, the first clinical trial of autologous CSCs for treatment of heart failure resulting from ischemic heart disease (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) has been conducted, and the interim results are quite promising. In this phase I trial, no adverse effects attributable to the CSC treatment have been noted, and CSC-treated patients showed a significant improvement in ejection fraction at 1 year (+13.7 absolute units versus baseline), accompanied by a 30.2 % reduction in infarct size. Moreover, the CSC-induced enhancement in cardiac structure and function was associated with a significant improvement in the New York Heart Association (NYHA) functional class and in the quality of life, as measured by the Minnesota Living with Heart failure Questionnaire. These results are exciting and warrant larger, phase II studies. However, CSC therapy for cardiac repair is still in its infancy, and many hurdles need to be overcome to further enhance the therapeutic efficacy of CSCs.
Literature
1.
go back to reference Go AS et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–245.PubMedCrossRef Go AS et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–245.PubMedCrossRef
2.
go back to reference Sanganalmath SK, Bolli R. Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res. 2013;113(6):810–34.PubMedCrossRef Sanganalmath SK, Bolli R. Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res. 2013;113(6):810–34.PubMedCrossRef
3.
go back to reference Beltrami AP et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763–76.PubMedCrossRef Beltrami AP et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763–76.PubMedCrossRef
4.
go back to reference Rumyantsev PP. Interrelations of the proliferation and differentiation processes during cardiact myogenesis and regeneration. Int Rev Cytol. 1977;51:186–273.PubMed Rumyantsev PP. Interrelations of the proliferation and differentiation processes during cardiact myogenesis and regeneration. Int Rev Cytol. 1977;51:186–273.PubMed
5.
go back to reference Cameron IL, Thrasher JD. Cellular and molecular renewal in the mammalian body. In: Cell biology. New York: Academic Press; 1971. p. xiv. 418 p. Cameron IL, Thrasher JD. Cellular and molecular renewal in the mammalian body. In: Cell biology. New York: Academic Press; 1971. p. xiv. 418 p.
6.
7.
go back to reference Shafiq SA, Gorycki MA, Mauro A. Mitosis during postnatal growth in skeletal and cardiac muscle of the rat. J Anat. 1968;103(Pt 1):135–41.PubMedCentralPubMed Shafiq SA, Gorycki MA, Mauro A. Mitosis during postnatal growth in skeletal and cardiac muscle of the rat. J Anat. 1968;103(Pt 1):135–41.PubMedCentralPubMed
8.
go back to reference Hsieh PC et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med. 2007;13(8):970–4.PubMedCentralPubMedCrossRef Hsieh PC et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med. 2007;13(8):970–4.PubMedCentralPubMedCrossRef
9.
go back to reference Sohal DS et al. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res. 2001;89(1):20–5.PubMedCrossRef Sohal DS et al. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res. 2001;89(1):20–5.PubMedCrossRef
10.
go back to reference Novak A et al. Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis. 2000;28(3–4):147–55.PubMedCrossRef Novak A et al. Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis. 2000;28(3–4):147–55.PubMedCrossRef
11.
go back to reference Morrison SJ et al. Identification of a lineage of multipotent hematopoietic progenitors. Development. 1997;124(10):1929–39.PubMed Morrison SJ et al. Identification of a lineage of multipotent hematopoietic progenitors. Development. 1997;124(10):1929–39.PubMed
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference Linke A et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A. 2005;102(25):8966–71.PubMedCentralPubMedCrossRef Linke A et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A. 2005;102(25):8966–71.PubMedCentralPubMedCrossRef
16.
go back to reference Anversa P et al. Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation. 2006;113(11):1451–63.PubMedCrossRef Anversa P et al. Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation. 2006;113(11):1451–63.PubMedCrossRef
17.
18.
go back to reference Yang L et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature. 2008;453(7194):524–8.PubMedCrossRef Yang L et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature. 2008;453(7194):524–8.PubMedCrossRef
19.
go back to reference Wang X et al. The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling. Stem Cells. 2006;24(7):1779–88.PubMedCrossRef Wang X et al. The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling. Stem Cells. 2006;24(7):1779–88.PubMedCrossRef
20.
go back to reference Oh H et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A. 2003;100(21):12313–8.PubMedCentralPubMedCrossRef Oh H et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A. 2003;100(21):12313–8.PubMedCentralPubMedCrossRef
21.
go back to reference Hierlihy AM et al. The post-natal heart contains a myocardial stem cell population. FEBS Lett. 2002;530(1–3):239–43.PubMedCrossRef Hierlihy AM et al. The post-natal heart contains a myocardial stem cell population. FEBS Lett. 2002;530(1–3):239–43.PubMedCrossRef
22.
go back to reference Pfister O et al. CD31- but not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res. 2005;97(1):52–61.PubMedCrossRef Pfister O et al. CD31- but not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res. 2005;97(1):52–61.PubMedCrossRef
23.
go back to reference Oyama T et al. Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. J Cell Biol. 2007;176(3):329–41.PubMedCentralPubMedCrossRef Oyama T et al. Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. J Cell Biol. 2007;176(3):329–41.PubMedCentralPubMedCrossRef
24.
go back to reference Messina E et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95(9):911–21.PubMedCrossRef Messina E et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95(9):911–21.PubMedCrossRef
25.
go back to reference Smith RR et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115(7):896–908.PubMedCrossRef Smith RR et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115(7):896–908.PubMedCrossRef
26.
go back to reference Johnston PV et al. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation. 2009;120(12):1075–83. 7 p following 1083.PubMedCentralPubMedCrossRef Johnston PV et al. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation. 2009;120(12):1075–83. 7 p following 1083.PubMedCentralPubMedCrossRef
27.
go back to reference Wessels A, Perez-Pomares JM. The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec A: Discov Mol Cell Evol Biol. 2004;276(1):43–57.CrossRef Wessels A, Perez-Pomares JM. The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec A: Discov Mol Cell Evol Biol. 2004;276(1):43–57.CrossRef
30.
32.
go back to reference Muller P et al. Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation. 2002;106(1):31–5.PubMedCrossRef Muller P et al. Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation. 2002;106(1):31–5.PubMedCrossRef
33.
go back to reference Thiele J et al. Mixed chimerism of cardiomyocytes and vessels after allogeneic bone marrow and stem-cell transplantation in comparison with cardiac allografts. Transplantation. 2004;77(12):1902–5.PubMedCrossRef Thiele J et al. Mixed chimerism of cardiomyocytes and vessels after allogeneic bone marrow and stem-cell transplantation in comparison with cardiac allografts. Transplantation. 2004;77(12):1902–5.PubMedCrossRef
34.
go back to reference Deb A et al. Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation. 2003;107(9):1247–9.PubMedCrossRef Deb A et al. Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation. 2003;107(9):1247–9.PubMedCrossRef
35.
go back to reference Fazel S et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest. 2006;116(7):1865–77.PubMedCentralPubMedCrossRef Fazel S et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest. 2006;116(7):1865–77.PubMedCentralPubMedCrossRef
36.
go back to reference Fujita J et al. Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair. Stem Cells. 2007;25(11):2750–9.PubMedCrossRef Fujita J et al. Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair. Stem Cells. 2007;25(11):2750–9.PubMedCrossRef
37.
go back to reference Wang Y et al. Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts. J Mol Cell Cardiol. 2006;41(3):478–87.PubMedCrossRef Wang Y et al. Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts. J Mol Cell Cardiol. 2006;41(3):478–87.PubMedCrossRef
38.
39.•
go back to reference Ellison GM et al. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell. 2013;154(4):827–42. This study used a reversible myocardial injury model in conjuction with different genetic approaches to examine the contribution of endogenous c-kit+ cardiac stem cells to myocardial renewal. Using a genetic fate mapping approach to demonstrate that new cardiomyocytes originate from endogenous c-kit+ cardiac stem cells via direct differentiation.PubMedCrossRef Ellison GM et al. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell. 2013;154(4):827–42. This study used a reversible myocardial injury model in conjuction with different genetic approaches to examine the contribution of endogenous c-kit+ cardiac stem cells to myocardial renewal. Using a genetic fate mapping approach to demonstrate that new cardiomyocytes originate from endogenous c-kit+ cardiac stem cells via direct differentiation.PubMedCrossRef
40.••
go back to reference Bolli R et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378(9806):1847–57. This is the first interim report on the phase I clinical trial (SCIPIO) of c-kit+/Lin- cardiac stem cells.PubMedCentralPubMedCrossRef Bolli R et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378(9806):1847–57. This is the first interim report on the phase I clinical trial (SCIPIO) of c-kit+/Lin- cardiac stem cells.PubMedCentralPubMedCrossRef
41.•
go back to reference Tang XL et al. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation. 2010;121(2):293–305. This study demonstrated that infusion of c-kit+/Lin- cardiac stem/progenitor cells is effective in improving the cardiac functions in a more clinically relevant setting using a chronic myocardial infarction model.PubMedCentralPubMedCrossRef Tang XL et al. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation. 2010;121(2):293–305. This study demonstrated that infusion of c-kit+/Lin- cardiac stem/progenitor cells is effective in improving the cardiac functions in a more clinically relevant setting using a chronic myocardial infarction model.PubMedCentralPubMedCrossRef
42.
go back to reference Li Q, et al. Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models. Basic Res Cardiol. 2011. Li Q, et al. Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models. Basic Res Cardiol. 2011.
43.
go back to reference Rota M et al. Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circ Res. 2008;103(1):107–16.PubMedCentralPubMedCrossRef Rota M et al. Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circ Res. 2008;103(1):107–16.PubMedCentralPubMedCrossRef
44.•
go back to reference Bolli R et al. Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation. 2013;128(2):122–31. This study examined the therapeutic efficacy of c-kit/Lin- cardiac stem cells using a preclinical large animal model of ischemic cardiomyopathy.PubMedCrossRef Bolli R et al. Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation. 2013;128(2):122–31. This study examined the therapeutic efficacy of c-kit/Lin- cardiac stem cells using a preclinical large animal model of ischemic cardiomyopathy.PubMedCrossRef
45.
go back to reference Williams AR et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013;127(2):213–23.PubMedCentralPubMedCrossRef Williams AR et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013;127(2):213–23.PubMedCentralPubMedCrossRef
46.
47.
go back to reference Rota M et al. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res. 2006;99(1):42–52.PubMedCrossRef Rota M et al. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res. 2006;99(1):42–52.PubMedCrossRef
48.
go back to reference Kajstura J et al. Cardiac stem cells and myocardial disease. J Mol Cell Cardiol. 2008;45(4):505–13.PubMedCrossRef Kajstura J et al. Cardiac stem cells and myocardial disease. J Mol Cell Cardiol. 2008;45(4):505–13.PubMedCrossRef
49.
go back to reference De Angelis A et al. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation. 2010;121(2):276–92.PubMedCentralPubMedCrossRef De Angelis A et al. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation. 2010;121(2):276–92.PubMedCentralPubMedCrossRef
50.
go back to reference Rona G et al. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959;67(4):443–55.PubMed Rona G et al. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959;67(4):443–55.PubMed
51.
go back to reference Joyner AL, Zervas M. Genetic inducible fate mapping in mouse: establishing genetic lineages and defining genetic neuroanatomy in the nervous system. Dev Dyn. 2006;235(9):2376–85.PubMedCrossRef Joyner AL, Zervas M. Genetic inducible fate mapping in mouse: establishing genetic lineages and defining genetic neuroanatomy in the nervous system. Dev Dyn. 2006;235(9):2376–85.PubMedCrossRef
55.
go back to reference van Berlo JH et al. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature. 2014;509(7500):337-41. van Berlo JH et al. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature. 2014;509(7500):337-41.
56.
go back to reference Fischer KM et al. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase. Circulation. 2009;120(21):2077–87.PubMedCentralPubMedCrossRef Fischer KM et al. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase. Circulation. 2009;120(21):2077–87.PubMedCentralPubMedCrossRef
57.
go back to reference Angert D et al. Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells. Circ Res. 2011;108(10):1226–37.PubMedCentralPubMedCrossRef Angert D et al. Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells. Circ Res. 2011;108(10):1226–37.PubMedCentralPubMedCrossRef
58.
go back to reference Dawn B et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A. 2005;102(10):3766–71.PubMedCentralPubMedCrossRef Dawn B et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A. 2005;102(10):3766–71.PubMedCentralPubMedCrossRef
59.••
go back to reference Chugh AR et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012;126(11 Suppl 1):S54–64. This report provides more updated information on the progress of the SCIPIO trial and includes MRI-based analysis of cardiac stem cell-treated patients.PubMedCentralPubMedCrossRef Chugh AR et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012;126(11 Suppl 1):S54–64. This report provides more updated information on the progress of the SCIPIO trial and includes MRI-based analysis of cardiac stem cell-treated patients.PubMedCentralPubMedCrossRef
60.
go back to reference Tang YL et al. Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol. 2005;46(7):1339–50.PubMedCrossRef Tang YL et al. Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol. 2005;46(7):1339–50.PubMedCrossRef
62.
go back to reference Reinecke H et al. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation. 1999;100(2):193–202.PubMedCrossRef Reinecke H et al. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation. 1999;100(2):193–202.PubMedCrossRef
63.
go back to reference Toma C et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93–8.PubMedCrossRef Toma C et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93–8.PubMedCrossRef
65.
go back to reference Schachinger V et al. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation. 2008;118(14):1425–32.PubMedCrossRef Schachinger V et al. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation. 2008;118(14):1425–32.PubMedCrossRef
66.
go back to reference Haider H, Ashraf M. Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation. J Mol Cell Cardiol. 2008;45(4):554–66.PubMedCentralPubMedCrossRef Haider H, Ashraf M. Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation. J Mol Cell Cardiol. 2008;45(4):554–66.PubMedCentralPubMedCrossRef
67.
go back to reference Hong KU et al. A highly sensitive and accurate method to quantify absolute numbers of c-kit+ cardiac stem cells following transplantation in mice. Basic Res Cardiol. 2013;108(3):346.PubMedCentralPubMedCrossRef Hong KU et al. A highly sensitive and accurate method to quantify absolute numbers of c-kit+ cardiac stem cells following transplantation in mice. Basic Res Cardiol. 2013;108(3):346.PubMedCentralPubMedCrossRef
68.
go back to reference Forrester JS, Libby P. The inflammation hypothesis and its potential relevance to statin therapy. Am J Cardiol. 2007;99(5):732–8.PubMedCrossRef Forrester JS, Libby P. The inflammation hypothesis and its potential relevance to statin therapy. Am J Cardiol. 2007;99(5):732–8.PubMedCrossRef
70.
go back to reference Ma K et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell. 1993;75(7):1287–95.PubMedCrossRef Ma K et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell. 1993;75(7):1287–95.PubMedCrossRef
71.
go back to reference Chai NN et al. Structure and organization of the RBMY genes on the human Y chromosome: transposition and amplification of an ancestral autosomal hnRNPG gene. Genomics. 1998;49(2):283–9.PubMedCrossRef Chai NN et al. Structure and organization of the RBMY genes on the human Y chromosome: transposition and amplification of an ancestral autosomal hnRNPG gene. Genomics. 1998;49(2):283–9.PubMedCrossRef
72.
go back to reference Muraski JA et al. Pim-1 regulates cardiomyocyte survival downstream of Akt. Nat Med. 2007;13(12):1467–75.PubMedCrossRef Muraski JA et al. Pim-1 regulates cardiomyocyte survival downstream of Akt. Nat Med. 2007;13(12):1467–75.PubMedCrossRef
73.
go back to reference Wang Z et al. Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis. J Vet Sci. 2001;2(3):167–79.PubMed Wang Z et al. Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis. J Vet Sci. 2001;2(3):167–79.PubMed
74.
go back to reference Wu JC et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation. 2003;108(11):1302–5.PubMedCrossRef Wu JC et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation. 2003;108(11):1302–5.PubMedCrossRef
75.
go back to reference Cottage CT et al. Increased mitotic rate coincident with transient telomere lengthening resulting from pim-1 overexpression in cardiac progenitor cells. Stem Cells. 2012;30(11):2512–22.PubMedCentralPubMedCrossRef Cottage CT et al. Increased mitotic rate coincident with transient telomere lengthening resulting from pim-1 overexpression in cardiac progenitor cells. Stem Cells. 2012;30(11):2512–22.PubMedCentralPubMedCrossRef
76.
go back to reference Xu M, Millard RW, Ashraf M. Role of GATA-4 in differentiation and survival of bone marrow mesenchymal stem cells. Prog Mol Biol Transl Sci. 2012;111:217–41.PubMedCrossRef Xu M, Millard RW, Ashraf M. Role of GATA-4 in differentiation and survival of bone marrow mesenchymal stem cells. Prog Mol Biol Transl Sci. 2012;111:217–41.PubMedCrossRef
77.
go back to reference Huang W et al. Mesenchymal stem cells overexpressing CXCR4 attenuate remodeling of postmyocardial infarction by releasing matrix metalloproteinase-9. Stem Cells Dev. 2012;21(5):778–89.PubMedCentralPubMedCrossRef Huang W et al. Mesenchymal stem cells overexpressing CXCR4 attenuate remodeling of postmyocardial infarction by releasing matrix metalloproteinase-9. Stem Cells Dev. 2012;21(5):778–89.PubMedCentralPubMedCrossRef
78.
go back to reference Mangi AA et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 2003;9(9):1195–201.PubMedCrossRef Mangi AA et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 2003;9(9):1195–201.PubMedCrossRef
79.
go back to reference Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999;13(22):2905–27.PubMedCrossRef Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999;13(22):2905–27.PubMedCrossRef
80.
go back to reference Fujio Y et al. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation. 2000;101(6):660–7.PubMedCentralPubMedCrossRef Fujio Y et al. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation. 2000;101(6):660–7.PubMedCentralPubMedCrossRef
81.
go back to reference Melo LG et al. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation. 2002;105(5):602–7.PubMedCrossRef Melo LG et al. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation. 2002;105(5):602–7.PubMedCrossRef
82.
go back to reference Vulapalli SR et al. Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol. 2002;283(2):H688–94.PubMed Vulapalli SR et al. Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol. 2002;283(2):H688–94.PubMed
83.
go back to reference McGinley LM et al. Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression. Hum Gene Ther. 2013;24(10):840–51.PubMedCrossRef McGinley LM et al. Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression. Hum Gene Ther. 2013;24(10):840–51.PubMedCrossRef
84.
go back to reference Huang F et al. Overexpression of MicroRNA-1 improves the efficacy of mesenchymal stem cell transplantation after myocardial infarction. Cardiology. 2013;125(1):18–30.PubMedCrossRef Huang F et al. Overexpression of MicroRNA-1 improves the efficacy of mesenchymal stem cell transplantation after myocardial infarction. Cardiology. 2013;125(1):18–30.PubMedCrossRef
85.
go back to reference Wang L et al. Protein kinase G1 alpha overexpression increases stem cell survival and cardiac function after myocardial infarction. PLoS ONE. 2013;8(3):e60087.PubMedCentralPubMedCrossRef Wang L et al. Protein kinase G1 alpha overexpression increases stem cell survival and cardiac function after myocardial infarction. PLoS ONE. 2013;8(3):e60087.PubMedCentralPubMedCrossRef
86.
go back to reference Shan Y et al. Induction of the heme oxygenase-1 gene by metalloporphyrins. Arch Biochem Biophys. 2000;380(2):219–27.PubMedCrossRef Shan Y et al. Induction of the heme oxygenase-1 gene by metalloporphyrins. Arch Biochem Biophys. 2000;380(2):219–27.PubMedCrossRef
87.
go back to reference Cai C et al. The heme oxygenase 1 inducer (CoPP) protects human cardiac stem cells against apoptosis through activation of the extracellular signal-regulated kinase (ERK)/NRF2 signaling pathway and cytokine release. J Biol Chem. 2012;287(40):33720–32.PubMedCentralPubMedCrossRef Cai C et al. The heme oxygenase 1 inducer (CoPP) protects human cardiac stem cells against apoptosis through activation of the extracellular signal-regulated kinase (ERK)/NRF2 signaling pathway and cytokine release. J Biol Chem. 2012;287(40):33720–32.PubMedCentralPubMedCrossRef
89.
go back to reference Zafir A et al. Protein O-GlcNAcylation is a novel cytoprotective signal in cardiac stem cells. Stem Cells. 2013;31(4):765–75.PubMedCrossRef Zafir A et al. Protein O-GlcNAcylation is a novel cytoprotective signal in cardiac stem cells. Stem Cells. 2013;31(4):765–75.PubMedCrossRef
90.
go back to reference Ye L et al. Thymosin beta4 Increases the potency of transplanted mesenchymal stem cells for myocardial repair. Circulation. 2013;128(26 Suppl 1):S32–41.PubMedCrossRef Ye L et al. Thymosin beta4 Increases the potency of transplanted mesenchymal stem cells for myocardial repair. Circulation. 2013;128(26 Suppl 1):S32–41.PubMedCrossRef
91.
go back to reference Iso Y, et al. Priming with ligands secreted by human stromal progenitor cells promotes grafts of cardiac stem/progenitor cells after myocardial infarction. Stem Cells. 2013. Iso Y, et al. Priming with ligands secreted by human stromal progenitor cells promotes grafts of cardiac stem/progenitor cells after myocardial infarction. Stem Cells. 2013.
92.
go back to reference Herrmann JL et al. Preconditioning mesenchymal stem cells with transforming growth factor-alpha improves mesenchymal stem cell-mediated cardioprotection. Shock. 2010;33(1):24–30.PubMedCrossRef Herrmann JL et al. Preconditioning mesenchymal stem cells with transforming growth factor-alpha improves mesenchymal stem cell-mediated cardioprotection. Shock. 2010;33(1):24–30.PubMedCrossRef
93.
go back to reference Penna C et al. Pharmacologically active microcarriers influence VEGF-A effects on mesenchymal stem cell survival. J Cell Mol Med. 2013;17(1):192–204.PubMedCrossRef Penna C et al. Pharmacologically active microcarriers influence VEGF-A effects on mesenchymal stem cell survival. J Cell Mol Med. 2013;17(1):192–204.PubMedCrossRef
94.
go back to reference Pendergrass KD et al. Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances angiogenic pathways following ischemia-reperfusion injury. Stem Cells Dev. 2013;22(17):2414–24.PubMedCrossRef Pendergrass KD et al. Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances angiogenic pathways following ischemia-reperfusion injury. Stem Cells Dev. 2013;22(17):2414–24.PubMedCrossRef
96.
97.
go back to reference Ebelt H et al. Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines. Stem Cells. 2007;25(1):236–44.PubMedCrossRef Ebelt H et al. Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines. Stem Cells. 2007;25(1):236–44.PubMedCrossRef
98.
go back to reference Chimenti I et al. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010;106(5):971–80.PubMedCrossRef Chimenti I et al. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010;106(5):971–80.PubMedCrossRef
99.
go back to reference Yoon CH et al. Mechanism of improved cardiac function after bone marrow mononuclear cell therapy: role of cardiovascular lineage commitment. Circulation. 2010;121(18):2001–11.PubMedCrossRef Yoon CH et al. Mechanism of improved cardiac function after bone marrow mononuclear cell therapy: role of cardiovascular lineage commitment. Circulation. 2010;121(18):2001–11.PubMedCrossRef
100.•
go back to reference Behfar A et al. Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol. 2010;56(9):721–34. This study showed that donor MSCs can be successfully primed or guided ex vivo to become cardiogenic, and that cardiogenic MSCs exhibit superior therapeutic efficacy against ischemic cardiomyopathy.PubMedCentralPubMedCrossRef Behfar A et al. Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol. 2010;56(9):721–34. This study showed that donor MSCs can be successfully primed or guided ex vivo to become cardiogenic, and that cardiogenic MSCs exhibit superior therapeutic efficacy against ischemic cardiomyopathy.PubMedCentralPubMedCrossRef
Metadata
Title
Cardiac Stem Cell Therapy for Cardiac Repair
Authors
Kyung U. Hong, Ph.D.
Roberto Bolli, M.D.
Publication date
01-07-2014
Publisher
Springer US
Published in
Current Treatment Options in Cardiovascular Medicine / Issue 7/2014
Print ISSN: 1092-8464
Electronic ISSN: 1534-3189
DOI
https://doi.org/10.1007/s11936-014-0324-3

Other articles of this Issue 7/2014

Current Treatment Options in Cardiovascular Medicine 7/2014 Go to the issue

Regenerative Medicine and Stem-cell Therapy (S Wu and P Hsieh, Section Editors)

Pluripotent Stem Cell Derived Cardiomyocytes for Cardiac Repair

Vascular Disease (R Schainfeld, Section Editor)

The Role of Renal Denervation in the Treatment of Hypertension

Regenerative Medicine and Stem-cell Therapy (S Wu and P Hsieh, Section Editors)

Mesenchymal Stem Cell Therapy for Cardiac Repair

Regenerative Medicine and Stem-cell Therapy (S Wu and P Hsieh, Section Editors)

hiPSC Modeling of Inherited Cardiomyopathies