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Myocardial Regenerative Medicine

  • Zhaobo Fan
  • Xiaofei Li
  • Hong Niu
  • Jianjun GuanEmail author
Chapter

Abstract

Myocardial infarction (MI) or heart attack has high mortality rate. It is characterized by massive cardiomyocyte death and reduced cardiac function. MI is a major cause of heart failure. Effective therapies are critical to prevent infarcted heart from progressing into heart failure. Current clinical intervention after MI is mainly focused on coronary reperfusion with the purpose of reintroducing nutrient and oxygen into the damaged area. Yet reperfusion therapy cannot induce the regeneration of new cardiac muscle, and the damaged heart tissue cannot self-regenerate to restore normal tissue features and function. To fully restore cardiac function, transplantation of cells to compensate the lost cardiac cells is necessary. Therapies that improve the function of damaged heart tissue other than fully regeneration have also been explored. These include using acellular biomaterials and control of cardiac fibrosis. This chapter summarizes current approaches for cardiac regeneration and cardiac function improvement.

Keywords

Myocardial infarction Cell therapy Biomaterials therapy Antifibrotic therapy 

Notes

Acknowledgments

This work was supported by the US National Institutes of Health (R01EB022018, R01HL124122, and R21EB021896), US National Science Foundation (1006734 and 1160122), and American Heart Association (15GRNT25830058 and 13GRNT17150041).

References

  1. 1.
    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics – 2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322.PubMedCrossRefGoogle Scholar
  2. 2.
    Wang F, Li Z, Khan M, Tamama K, Kuppusamy P, Wagner WR, et al. Injectable, rapid gelling and highly flexible hydrogel composites as growth factor and cell carriers. Acta Biomater. 2010;6:1978–91.PubMedCrossRefGoogle Scholar
  3. 3.
    Li Z, Guan J. Hydrogels for cardiac tissue engineering. Polymers. 2011;3:740–61.CrossRefGoogle Scholar
  4. 4.
    Etzion S, Kedes LH, Kloner RA, Leor J. Myocardial regeneration: present and future trends. Am J Cardiovasc Drugs: Drugs, Devices, Other Interv. 2001;1:233–44.CrossRefGoogle Scholar
  5. 5.
    Mann DL. Mechanisms and models in heart failure: a combinatorial approach. Circulation. 1999;100:999–1008.PubMedCrossRefGoogle Scholar
  6. 6.
    Kim D-H, Kim P, Song I, Cha JM, Lee SH, Kim B, et al. Guided three-dimensional growth of functional cardiomyocytes on polyethylene glycol nanostructures. Langmuir. 2006;22:5419–26.PubMedCrossRefGoogle Scholar
  7. 7.
    Wang RM, Christman KL. Decellularized myocardial matrix hydrogels: in basic research and preclinical studies. Adv Drug Deliv Rev. 2016;96:77–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Okada M, Payne TR, Oshima H, Momoi N, Tobita K, Huard J. Differential efficacy of gels derived from small intestinal submucosa as an injectable biomaterial for myocardial infarct repair. Biomaterials. 2010;31:7678–83.PubMedCrossRefGoogle Scholar
  9. 9.
    Seif-Naraghi SB, Singelyn JM, Salvatore MA, Osborn KG, Wang JJ, Sampat U, et al. Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction. Sci Transl Med. 2013;5:173ra25.PubMedCrossRefGoogle Scholar
  10. 10.
    Singelyn JM, Sundaramurthy P, Johnson TD, Schup-Magoffin PJ, Hu DP, Faulk DM, et al. Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction. J Am Coll Cardiol. 2012;59:751–63.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Chenite A, Chaput C, Wang D, Combes C, Buschmann M, Hoemann C, et al. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials. 2000;21:2155–61.PubMedCrossRefGoogle Scholar
  12. 12.
    Léobon B, Garcin I, Menasché P, Vilquin J-T, Audinat E, Charpak S. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci. 2003;100:7808–11.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Lu W-N, Lü S-H, Wang H-B, Li D-X, Duan C-M, Liu Z-Q, et al. Functional improvement of infarcted heart by co-injection of embryonic stem cells with temperature-responsive chitosan hydrogel. Tissue Eng Part A. 2008;15:1437–47.CrossRefGoogle Scholar
  14. 14.
    Liu Z, Wang H, Wang Y, Lin Q, Yao A, Cao F, et al. The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment. Biomaterials. 2012;33:3093–106.PubMedCrossRefGoogle Scholar
  15. 15.
    Ifkovits JL, Tous E, Minakawa M, Morita M, Robb JD, Koomalsingh KJ, et al. Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model. Proc Natl Acad Sci. 2010;107:11507–12.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Draget KI, Østgaard K, Smidsrød O. Homogeneous alginate gels: a technical approach. Carbohydr Polym. 1990;14:159–78.CrossRefGoogle Scholar
  17. 17.
    Landa N, Miller L, Feinberg MS, Holbova R, Shachar M, Freeman I, et al. Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat. Circulation. 2008;117:1388–96.PubMedCrossRefGoogle Scholar
  18. 18.
    Leor J, Tuvia S, Guetta V, Manczur F, Castel D, Willenz U, et al. Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine. J Am Coll Cardiol. 2009;54:1014–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Dahlmann J, Krause A, Möller L, Kensah G, Möwes M, Diekmann A, et al. Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for myocardial tissue engineering. Biomaterials. 2013;34:940–51.PubMedCrossRefGoogle Scholar
  20. 20.
    Tsur-Gang O, Ruvinov E, Landa N, Holbova R, Feinberg MS, Leor J, et al. The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction. Biomaterials. 2009;30:189–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Mukherjee R, Zavadzkas JA, Saunders SM, McLean JE, Jeffords LB, Beck C, et al. Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs. Ann Thorac Surg. 2008;86:1268–76.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005;15:378–86.PubMedCrossRefGoogle Scholar
  23. 23.
    Tai KF, Chen PJ, Chen DS, Hwang LH. Concurrent delivery of GM‐CSF and endostatin genes by a single adenoviral vector provides a synergistic effect on the treatment of orthotopic liver tumors. J Gene Med. 2003;5:386–98.PubMedCrossRefGoogle Scholar
  24. 24.
    Ou L, Li W, Zhang Y, Wang W, Liu J, Sorg H, et al. Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model. J Cell Mol Med. 2011;15:1310–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Li Z, Wang F, Roy S, Sen CK, Guan J. Injectable, highly flexible, and thermosensitive hydrogels capable of delivering superoxide dismutase. Biomacromolecules. 2009;10:3306–16.PubMedCrossRefGoogle Scholar
  26. 26.
    Xu G, Wang X, Deng C, Teng X, Suuronen EJ, Shen Z, et al. Injectable biodegradable hybrid hydrogels based on thiolated collagen and oligo (acryloyl carbonate)–poly (ethylene glycol)–oligo (acryloyl carbonate) copolymer for functional cardiac regeneration. Acta Biomater. 2015;15:55–64.PubMedCrossRefGoogle Scholar
  27. 27.
    Williams C, Budina E, Stoppel WL, Sullivan KE, Emani S, Emani SM, et al. Cardiac extracellular matrix–fibrin hybrid scaffolds with tunable properties for cardiovascular tissue engineering. Acta Biomater. 2015;14:84–95.PubMedCrossRefGoogle Scholar
  28. 28.
    Fujimoto KL, Ma Z, Nelson DM, Hashizume R, Guan J, Tobita K, et al. Synthesis, characterization and therapeutic efficacy of a biodegradable, thermoresponsive hydrogel designed for application in chronic infarcted myocardium. Biomaterials. 2009;30:4357–68.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Jiang XJ, Wang T, Li XY, Wu DQ, Zheng ZB, Zhang JF, et al. Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction. J Biomed Mater Res A. 2009;90:472–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Bawa P, Pillay V, Choonara YE, du Toit LC. Stimuli-responsive polymers and their applications in drug delivery. Biomed Mater (Bristol, England). 2009;4:022001.CrossRefGoogle Scholar
  31. 31.
    Crompton KE, Goud JD, Bellamkonda RV, Gengenbach TR, Finkelstein DI, Horne MK, et al. Polylysine-functionalised thermoresponsive chitosan hydrogel for neural tissue engineering. Biomaterials. 2007;28:441–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Davis ME, Hsieh PC, Takahashi T, Song Q, Zhang S, Kamm RD, et al. Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction. Proc Natl Acad Sci U S A. 2006;103:8155–60.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Li Y, Rodrigues J, Tomás H. Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem Soc Rev. 2012;41:2193–221.PubMedCrossRefGoogle Scholar
  34. 34.
    Guan J, Hong Y, Ma Z, Wagner WR. Protein-reactive, thermoresponsive copolymers with high flexibility and biodegradability. Biomacromolecules. 2008;9:1283–92.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Li H, Duann P, Lin PH, Zhao L, Fan Z, Tan T, et al. Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair. J Biol Chem. 2015;290:24592–603.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Li Z, Fan Z, Xu Y, Lo W, Wang X, Niu H, et al. pH-sensitive and thermosensitive hydrogels as stem-cell carriers for cardiac therapy. ACS Appl Mater Interfaces. 2016;8:10752–60.PubMedCrossRefGoogle Scholar
  37. 37.
    Li Z, Fan Z, Xu Y, Niu H, Xie X, Liu Z, et al. Thermosensitive and highly flexible hydrogels capable of stimulating cardiac differentiation of cardiosphere-derived cells under static and dynamic mechanical training conditions. ACS Appl Mater Interfaces. 2016;8:15948–57.PubMedCrossRefGoogle Scholar
  38. 38.
    Li Z, Guo X, Guan J. A thermosensitive hydrogel capable of releasing bFGF for enhanced differentiation of mesenchymal stem cell into cardiomyocyte-like cells under ischemic conditions. Biomacromolecules. 2012;13:1956–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Li Z, Guo X, Guan J. An oxygen release system to augment cardiac progenitor cell survival and differentiation under hypoxic condition. Biomaterials. 2012;33:5914–23.PubMedCrossRefGoogle Scholar
  40. 40.
    Li Z, Guo X, Matsushita S, Guan J. Differentiation of cardiosphere-derived cells into a mature cardiac lineage using biodegradable poly(N-isopropylacrylamide) hydrogels. Biomaterials. 2011;32:3220–32.PubMedCrossRefGoogle Scholar
  41. 41.
    Li Z, Guo X, Palmer AF, Das H, Guan J. High-efficiency matrix modulus-induced cardiac differentiation of human mesenchymal stem cells inside a thermosensitive hydrogel. Acta Biomater. 2012;8:3586–95.PubMedCrossRefGoogle Scholar
  42. 42.
    Wang F, Li Z, Lannutti JL, Wagner WR, Guan J. Synthesis, characterization and surface modification of low moduli poly(ether carbonate urethane)ureas for soft tissue engineering. Acta Biomater. 2009;5:2901–12.PubMedCrossRefGoogle Scholar
  43. 43.
    Xu Y, Fu M, Li Z, Fan Z, Li X, Liu Y, et al. A prosurvival and proangiogenic stem cell delivery system to promote ischemic limb regeneration. Acta Biomater. 2016;31:99–113.PubMedCrossRefGoogle Scholar
  44. 44.
    Xu Y, Li Z, Li X, Fan Z, Liu Z, Xie X, et al. Regulating myogenic differentiation of mesenchymal stem cells using thermosensitive hydrogels. Acta Biomater. 2015;26:23–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Nelson DM, Hashizume R, Yoshizumi T, Blakney AK, Ma Z, Wagner WR. Intramyocardial injection of a synthetic hydrogel with delivery of bFGF and IGF1 in a rat model of ischemic cardiomyopathy. Biomacromolecules. 2014;15:1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Yoshizumi T, Zhu Y, Jiang H, D'Amore A, Sakaguchi H, Tchao J, et al. Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction. Biomaterials. 2016;83:182–93.PubMedCrossRefGoogle Scholar
  47. 47.
    Wall ST, Yeh CC, Tu RY, Mann MJ, Healy KE. Biomimetic matrices for myocardial stabilization and stem cell transplantation. J Biomed Mater Res A. 2010;95:1055–66.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Garbern JC, Minami E, Stayton PS, Murry CE. Delivery of basic fibroblast growth factor with a pH-responsive, injectable hydrogel to improve angiogenesis in infarcted myocardium. Biomaterials. 2011;32:2407–16.PubMedCrossRefGoogle Scholar
  49. 49.
    Blackburn NJ, Sofrenovic T, Kuraitis D, Ahmadi A, McNeill B, Deng C, et al. Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction. Biomaterials. 2015;39:182–92.PubMedCrossRefGoogle Scholar
  50. 50.
    Holmes JW, Borg TK, Covell JW. Structure and mechanics of healing myocardial infarcts. Annu Rev Biomed Eng. 2005;7:223–53.PubMedCrossRefGoogle Scholar
  51. 51.
    Li X, Zhou J, Liu Z, Chen J, Lü S, Sun H, et al. A PNIPAAm-based thermosensitive hydrogel containing SWCNTs for stem cell transplantation in myocardial repair. Biomaterials. 2014;35:5679–88.PubMedCrossRefGoogle Scholar
  52. 52.
    Chen Y-S, Tsou P-C, Lo J-M, Tsai H-C, Wang Y-Z, Hsiue G-H. Poly (N-isopropylacrylamide) hydrogels with interpenetrating multiwalled carbon nanotubes for cell sheet engineering. Biomaterials. 2013;34:7328–34.PubMedCrossRefGoogle Scholar
  53. 53.
    Odian G. Principles of polymerization. Hoboken: Wiley; 2004.CrossRefGoogle Scholar
  54. 54.
    Kraehenbuehl TP, Ferreira LS, Hayward AM, Nahrendorf M, van der Vlies AJ, Vasile E, et al. Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction. Biomaterials. 2011;32:1102–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Wang T, Jiang XJ, Tang QZ, Li XY, Lin T, Wu DQ, et al. Bone marrow stem cells implantation with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel improves cardiac function after myocardial infarction. Acta Biomater. 2009;5:2939–44.PubMedCrossRefGoogle Scholar
  56. 56.
    French KM, Somasuntharam I, Davis ME. Self-assembling peptide-based delivery of therapeutics for myocardial infarction. Adv Drug Deliv Rev. 2016;96:40–53.PubMedCrossRefGoogle Scholar
  57. 57.
    Davis ME, Motion JP, Narmoneva DA, Takahashi T, Hakuno D, Kamm RD, et al. Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation. 2005;111:442–50.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Callegari A, Bollini S, Iop L, Chiavegato A, Torregrossa G, Pozzobon M, et al. Neovascularization induced by porous collagen scaffold implanted on intact and cryoinjured rat hearts. Biomaterials. 2007;28:5449–61.PubMedCrossRefGoogle Scholar
  59. 59.
    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;13:2063–71.PubMedCrossRefGoogle Scholar
  60. 60.
    Tan MY, Zhi W, Wei RQ, Huang YC, Zhou KP, Tan B, et al. Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits. Biomaterials. 2009;30:3234–40.PubMedCrossRefGoogle Scholar
  61. 61.
    Fujimoto KL, Tobita K, Merryman WD, Guan J, Momoi N, Stolz DB, et al. An elastic, biodegradable cardiac patch induces contractile smooth muscle and improves cardiac remodeling and function in subacute myocardial infarction. J Am Coll Cardiol. 2007;49:2292–300.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Fujimoto KL, Tobita K, Guan J, Hashizume R, Takanari K, Alfieri CM, et al. Placement of an elastic biodegradable cardiac patch on a subacute infarcted heart leads to cellularization with early developmental cardiomyocyte characteristics. J Card Fail. 2012;18:585–95.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Piao H, Kwon JS, Piao S, Sohn JH, Lee YS, Bae JW, et al. Effects of cardiac patches engineered with bone marrow-derived mononuclear cells and PGCL scaffolds in a rat myocardial infarction model. Biomaterials. 2007;28:641–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Jin J, Jeong SI, Shin YM, Lim KS, Shin H, Lee YM, et al. Transplantation of mesenchymal stem cells within a poly(lactide-co-epsilon-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model. Eur J Heart Fail. 2009;11:147–53.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Hosoda T, Zheng H, Cabral-da-Silva M, Sanada F, Ide-Iwata N, Ogorek B, et al. Human cardiac stem cell differentiation is regulated by a mircrine mechanism. Circulation. 2011;123:1287–96.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Chugh AR, Beache GM, Loughran JH, Mewton N, Elmore JB, Kajstura J, 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:S54–64.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Bolli R, Tang XL, Sanganalmath SK, Rimoldi O, Mosna F, Abdel-Latif A, et al. Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation. 2013;128:122–31.PubMedCrossRefGoogle Scholar
  68. 68.
    Latham N, Ye B, Jackson R, Lam BK, Kuraitis D, Ruel M, et al. Human blood and cardiac stem cells synergize to enhance cardiac repair when cotransplanted into ischemic myocardium. Circulation. 2013;128:S105–12.PubMedCrossRefGoogle Scholar
  69. 69.
    Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, 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;127:213–23.PubMedCrossRefGoogle Scholar
  70. 70.
    Spater D, Abramczuk MK, Buac K, Zangi L, Stachel MW, Clarke J, et al. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol. 2013;15:1098–106.PubMedCrossRefGoogle Scholar
  71. 71.
    Nsair A, Schenke-Layland K, Van Handel B, Evseenko D, Kahn M, Zhao P, et al. Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells. PLoS One. 2012;7:e45603.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Hudson J, Titmarsh D, Hidalgo A, Wolvetang E, Cooper-White J. Primitive cardiac cells from human embryonic stem cells. Stem Cells Dev. 2012;21:1513–23.PubMedCrossRefGoogle Scholar
  73. 73.
    Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115:896–908.PubMedCrossRefGoogle Scholar
  74. 74.
    Davis DR, Zhang Y, Smith RR, Cheng K, Terrovitis J, Malliaras K, et al. Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue. PLoS One. 2009;4:e7195.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Johnston PV, Sasano T, Mills K, Evers R, Lee ST, Smith RR, et al. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation. 2009;120:1075–83.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Chimenti I, Smith RR, Li TS, Gerstenblith G, Messina E, Giacomello A, et al. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010;106:971–80.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Mishra R, Vijayan K, Colletti EJ, Harrington DA, Matthiesen TS, Simpson D, et al. Characterization and functionality of cardiac progenitor cells in congenital heart patients. Circulation. 2011;123:364–73.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Li TS, Cheng K, Malliaras K, Smith RR, Zhang Y, Sun B, et al. Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol. 2012;59:942–53.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Maxeiner H, Mufti S, Krehbiehl N, Dulfer F, Helmig S, Schneider J, et al. Interleukin-6 contributes to the paracrine effects of cardiospheres cultured from human, murine and rat hearts. J Cell Physiol. 2014;229:1681–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Xie Y, Ibrahim A, Cheng K, Wu Z, Liang W, Malliaras K, et al. Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells. Stem Cells (Dayton, Ohio). 2014;32:2397–406.CrossRefGoogle Scholar
  81. 81.
    Davis DR, Kizana E, Terrovitis J, Barth AS, Zhang YQ, Smith RR, et al. Isolation and expansion of functionally-competent cardiac progenitor cells directly from heart biopsies. J Mol Cell Cardiol. 2010;49:312–21.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Davis DR, Zhang YQ, Smith RR, Cheng K, Terrovitis J, Malliaras K, et al. Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue. Plos One. 2009;4:e7195.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Lee ST, White AJ, Matsushita S, Malliaras K, Steenbergen C, Zhang Y, et al. Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction. J Am Coll Cardiol. 2011;57:455–65.PubMedCrossRefGoogle Scholar
  84. 84.
    Forrester JS, Makkar RR, Marban E. Long-term outcome of stem cell therapy for acute myocardial infarction: right results, wrong reasons. J Am Coll Cardiol. 2009;53:2270–2.PubMedCrossRefGoogle Scholar
  85. 85.
    Wang F, Guan J. Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy. Adv Drug Deliv Rev. 2010;62:784–97.PubMedCrossRefGoogle Scholar
  86. 86.
    Don CW, Murry CE. Improving survival and efficacy of pluripotent stem cell-derived cardiac grafts. J Cell Mol Med. 2013;17:1355–62.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Tang YL, Wang YJ, Chen LJ, Pan YH, Zhang L, Weintraub NL. Cardiac-derived stem cell-based therapy for heart failure: progress and clinical applications. Expl Biol Med (Maywood, NJ). 2013;238:294–300.CrossRefGoogle Scholar
  88. 88.
    Garbern JC, Lee RT. Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell. 2013;12:689–98.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Rosen MR, Myerburg RJ, Francis DP, Cole GD, Marban E. Translating stem cell research to cardiac disease therapies: pitfalls and prospects for improvement. J Am Coll Cardiol. 2014;64:922–37.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    van Berlo JH, Molkentin JD. An emerging consensus on cardiac regeneration. Nat Med. 2014;20:1386–93.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Nagaya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y, et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 2005;112:1128–35.PubMedCrossRefGoogle Scholar
  92. 92.
    Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J: Off Publ Fed Am Soc Exp Biol. 2006;20:661–9.CrossRefGoogle Scholar
  93. 93.
    Ripa RS, Haack-Sorensen M, Wang Y, Jorgensen E, Mortensen S, Bindslev L, et al. Bone marrow derived mesenchymal cell mobilization by granulocyte-colony stimulating factor after acute myocardial infarction: results from the Stem Cells in Myocardial Infarction (STEMMI) trial. Circulation. 2007;116:I24–30.PubMedCrossRefGoogle Scholar
  94. 94.
    Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009;54:2277–86.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Traverse JH, McKenna DH, Harvey K, Jorgenso BC, Olson RE, Bostrom N, et al. Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction. Am Heart J. 2010;160:428–34.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Duran JM, Makarewich CA, Sharp TE, Starosta T, Zhu F, Hoffman NE, et al. Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms. Circ Res. 2013;113:539–52.PubMedCrossRefGoogle Scholar
  97. 97.
    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;105:93–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Balana B, Nicoletti C, Zahanich I, Graf EM, Christ T, Boxberger S, et al. 5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells. Cell Res. 2006;16:949–60.PubMedCrossRefGoogle Scholar
  99. 99.
    Qian Q, Qian H, Zhang X, Zhu W, Yan YM, Ye SQ, et al. 5-azacytidine induces cardiac differentiation of human umbilical cord-derived mesenchymal stem cells by activating extracellular regulated kinase. Stem Cells Dev. 2012;21:67–75.PubMedCrossRefGoogle Scholar
  100. 100.
    Wang CC, Chen CH, Lin WW, Hwang SM, Hsieh PCH, Lai PH, et al. Direct intramyocardial injection of mesenchymal stem cell sheet fragments improves cardiac functions after infarction. Cardiovasc Res. 2008;77:515–24.PubMedCrossRefGoogle Scholar
  101. 101.
    Martinez EC, Kofidis T. Adult stem cells for cardiac tissue engineering. J Mol Cell Cardiol. 2011;50:312–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Perin EC, Tian M, Marini FC, Silva GV, Zheng Y, Baimbridge F, et al. Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model. Plos One. 2011;6:e22949.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res. 2004;95:9–20.PubMedCrossRefGoogle Scholar
  104. 104.
    Mias C, Lairez O, Trouche E, Roncalli J, Calise D, Seguelas MH, et al. Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction. Stem Cells (Dayton, Ohio). 2009;27:2734–43.CrossRefGoogle Scholar
  105. 105.
    Zuo S, Jones WK, Li HX, He ZS, Pasha ZS, Yang YT, et al. Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injury. Stem Cells Dev. 2012;21:598–608.PubMedCrossRefGoogle Scholar
  106. 106.
    Mazo M, Planat-Benard V, Abizanda G, Pelacho B, Leobon B, Gavira JJ, et al. Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction. Eur J Heart Fail. 2008;10:454–62.PubMedCrossRefGoogle Scholar
  107. 107.
    Mazo M, Hernandez S, Gavira JJ, Abizanda G, Arana M, Lopez-Martinez T, et al. Treatment of reperfused ischemia with adipose-derived stem cells in a preclinical Swine model of myocardial infarction. Cell Transplant. 2012;21:2723–33.PubMedCrossRefGoogle Scholar
  108. 108.
    Shevchenko EK, Makarevich PI, Tsokolaeva ZI, Boldyreva MA, Sysoeva VY, Tkachuk VA, et al. Transplantation of modified human adipose derived stromal cells expressing VEGF165 results in more efficient angiogenic response in ischemic skeletal muscle. J Transl Med. 2013;11:138.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Rigol M, Solanes N, Roura S, Roque M, Novensa L, Dantas AP, et al. Allogeneic adipose stem cell therapy in acute myocardial infarction. Eur J Clin Invest. 2014;44:83–92.PubMedCrossRefGoogle Scholar
  110. 110.
    Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124:619–26.PubMedCrossRefGoogle Scholar
  111. 111.
    Baldi A, Abbate A, Bussani R, Patti G, Melfi R, Angelini A, et al. Apoptosis and post-infarction left ventricular remodeling. J Mol Cell Cardiol. 2002;34:165–74.PubMedCrossRefGoogle Scholar
  112. 112.
    Khoynezhad A, Jalali Z, Tortolani AJ. Apoptosis: pathophysiology and therapeutic implications for the cardiac surgeon. Ann Thorac Surg. 2004;78:1109–18.PubMedCrossRefGoogle Scholar
  113. 113.
    Reinecke H, Murry CE. Taking the death toll after cardiomyocyte grafting: a reminder of the importance of quantitative biology. J Mol Cell Cardiol. 2002;34:251–3.PubMedCrossRefGoogle Scholar
  114. 114.
    Li X, Tamama K, Xie X, Guan J. Improving cell engraftment in cardiac stem cell therapy. Stem Cells Int. 2016;2016:7168797.PubMedGoogle Scholar
  115. 115.
    Jiang S, Haider H, Idris NM, Salim A, Ashraf M. Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ Res. 2006;99:776–84.PubMedCrossRefGoogle Scholar
  116. 116.
    Maulik N, Yoshida T, Engelman RM, Deaton D, Flack 3rd JE, Rousou JA, et al. Ischemic preconditioning attenuates apoptotic cell death associated with ischemia/reperfusion. Mol Cell Biochem. 1998;186:139–45.PubMedCrossRefGoogle Scholar
  117. 117.
    Su J, Hu BH, Lowe Jr WL, Kaufman DB, Messersmith PB. Anti-inflammatory peptide-functionalized hydrogels for insulin-secreting cell encapsulation. Biomaterials. 2010;31:308–14.PubMedCrossRefGoogle Scholar
  118. 118.
    Kadner K, Dobner S, Franz T, Bezuidenhout D, Sirry MS, Zilla P, et al. The beneficial effects of deferred delivery on the efficiency of hydrogel therapy post myocardial infarction. Biomaterials. 2012;33:2060–6.PubMedCrossRefGoogle Scholar
  119. 119.
    Deuse T, Peter C, Fedak PWM, Doyle T, Reichenspurner H, Zimmermann WH, et al. Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation. 2009;120:S247–54.PubMedCrossRefGoogle Scholar
  120. 120.
    Lee TJ, Bhang SH, Yang HS, La WG, Yoon HH, Shin JY, et al. Enhancement of long-term angiogenic efficacy of adipose stem cells by delivery of FGF2. Microvasc Res. 2012;84:1–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Nor JE, Christensen J, Mooney DJ, Polverini PJ. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am J Pathol. 1999;154:375–84.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Lynch SE, Decastilla GR, Williams RC, Kiritsy CP, Howell TH, Reddy MS, et al. The effects of short-term application of a combination of platelet-derived and insulin-like growth-factors on periodontal wound-healing. J Periodontol. 1991;62:458–67.PubMedCrossRefGoogle Scholar
  123. 123.
    Nixon AJ, Brower-Toland BD, Bent SJ, Saxer RA, Wilke MJ, Robbins PD, et al. Insulinlike growth factor-I gene therapy applications for cartilage repair. Clin Orthop Rel Res. 2000;379:S201–13.Google Scholar
  124. 124.
    Martens TP, Godier AFG, Parks JJ, Wan LQ, Koeckert MS, Eng GM, et al. Percutaneous cell delivery into the heart using hydrogels polymerizing in situ. Cell Transplant. 2009;18:297–304.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Li Z, Guan J. Thermosensitive hydrogels for drug delivery. Expert Opin Drug Deliv. 2011;8:991–1007.PubMedCrossRefGoogle Scholar
  126. 126.
    Babensee JE, McIntire LV, Mikos AG. Growth factor delivery for tissue engineering. Pharm Res. 2000;17:497–504.PubMedCrossRefGoogle Scholar
  127. 127.
    Ma F, Xiao Z, Chen B, Hou X, Han J, Zhao Y, et al. Accelerating proliferation of neural stem/progenitor cells in collagen sponges immobilized with engineered basic fibroblast growth factor for nervous system tissue engineering. Biomacromolecules. 2014;15:1062–8.PubMedCrossRefGoogle Scholar
  128. 128.
    Chen Y, Xu H, Liu J, Zhang C, Leutz A, Mo X. The c-Myb functions as a downstream target of PDGF-mediated survival signal in vascular smooth muscle cells. Biochem Biophys Res Commun. 2007;360:433–6.PubMedCrossRefGoogle Scholar
  129. 129.
    Haider H, Ye L, Jiang S, Ge R, Law PK, Chua T, et al. Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor. J Mol Med (Berlin, Germany). 2004;82:539–49.CrossRefGoogle Scholar
  130. 130.
    Xu P, Liu J, Derynck R. Post-translational regulation of TGF-beta receptor and Smad signaling. FEBS Lett. 2012;586:1871–84.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Xue YY, Yan Y, Gong H, Fang B, Zhou Y, Ding ZW, et al. Insulin-like growth factor binding protein 4 enhances cardiomyocytes induction in murine-induced pluripotent stem cells. J Cell Biochem. 2014;115:1495–504.PubMedCrossRefGoogle Scholar
  132. 132.
    Minato A, Ise H, Goto M, Akaike T. Cardiac differentiation of embryonic stem cells by substrate immobilization of insulin-like growth factor binding protein 4 with elastin-like polypeptides. Biomaterials. 2012;33:515–23.PubMedCrossRefGoogle Scholar
  133. 133.
    Choi KC, Yoo DS, Cho KS, Huh PW, Kim DS, Park CK. Effect of single growth factor and growth factor combinations on differentiation of neural stem cells. J Korean Neurosurg Soc. 2008;44:375–81.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Koudstaal S, Bastings MM, Feyen DA, Waring CD, van Slochteren FJ, Dankers PY, et al. Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart. J Cardiovasc Transl Res. 2014;7:232–41.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Li RH. Materials for immunoisolated cell transplantation. Adv Drug Deliv Rev. 1998;33:87–109.PubMedCrossRefGoogle Scholar
  136. 136.
    Wilson JT, Chaikof EL. Challenges and emerging technologies in the immunoisolation of cells and tissues. Adv Drug Deliv Rev. 2008;60:124–45.PubMedCrossRefGoogle Scholar
  137. 137.
    Weber LM, Hayda KN, Anseth KS. Cell-matrix interactions improve beta-cell survival and insulin secretion in three-dimensional culture. Tissue Eng Part A. 2008;14:1959–68.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Weber LM, Anseth KS. Hydrogel encapsulation environments functionalized with extracellular matrix interactions increase islet insulin secretion. Matrix Biol: J Int Soc Matrix Biol. 2008;27:667–73.CrossRefGoogle Scholar
  139. 139.
    Lin CC, Anseth KS. Glucagon-like peptide-1 functionalized PEG hydrogels promote survival and function of encapsulated pancreatic beta-cells. Biomacromolecules. 2009;10:2460–7.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Shuh M, Bohorquez H, Loss Jr GE, Cohen AJ. Tumor necrosis factor-alpha: life and death of hepatocytes during liver ischemia/reperfusion injury. Ochsner J. 2013;13:119–30.PubMedPubMedCentralGoogle Scholar
  141. 141.
    de Vos P, Marchetti P. Encapsulation of pancreatic islets for transplantation in diabetes: the untouchable islets. Trends Mol Med. 2002;8:363–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Jang JY, Lee DY, Park SJ, Byun Y. Immune reactions of lymphocytes and macrophages against PEG-grafted pancreatic islets. Biomaterials. 2004;25:3663–9.PubMedCrossRefGoogle Scholar
  143. 143.
    Hume PS, Anseth KS. Polymerizable superoxide dismutase mimetic protects cells encapsulated in poly(ethylene glycol) hydrogels from reactive oxygen species-mediated damage. J Biomed Mater Res A. 2011;99:29–37.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Lin CC, Metters AT, Anseth KS. Functional PEG-peptide hydrogels to modulate local inflammation induced by the pro-inflammatory cytokine TNFalpha. Biomaterials. 2009;30:4907–14.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Guo J, Zheng D, Li WF, Li HR, Zhang AD, Li ZC. Insulin-like growth factor 1 treatment of MSCs attenuates inflammation and cardiac dysfunction following MI. Inflammation. 2014;37:2156–63.PubMedCrossRefGoogle Scholar
  146. 146.
    Eschenhagen T, Fink C, Remmers U, Scholz H, Wattchow J, Weil J, et al. Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. FASEB J. 1997;11:683–94.PubMedGoogle Scholar
  147. 147.
    Shapiro L, Cohen S. Novel alginate sponges for cell culture and transplantation. Biomaterials. 1997;18:583–90.PubMedCrossRefGoogle Scholar
  148. 148.
    Caspi O, Lesman A, Basevitch Y, Gepstein A, Arbel G, Huber I, et al. Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ Res. 2007;100:263–72.PubMedCrossRefGoogle Scholar
  149. 149.
    Engelmayr Jr GC, Cheng M, Bettinger CJ, Borenstein JT, Langer R, Freed LE. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat Mater. 2008;7:1003–10.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Masoumi N, Johnson KL, Howell MC, Engelmayr Jr GC. Valvular interstitial cell seeded poly(glycerol sebacate) scaffolds: toward a biomimetic in vitro model for heart valve tissue engineering. Acta Biomater. 2013;9:5974–88.PubMedCrossRefGoogle Scholar
  151. 151.
    Berry MF, Engler AJ, Woo YJ, Pirolli TJ, Bish LT, Jayasankar V, et al. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol. 2006;290:10.CrossRefGoogle Scholar
  152. 152.
    Joanne P, Kitsara M, Boitard SE, Naemetalla H, Vanneaux V, Pernot M, et al. Nanofibrous clinical-grade collagen scaffolds seeded with human cardiomyocytes induces cardiac remodeling in dilated cardiomyopathy. Biomaterials. 2016;80:157–68.PubMedCrossRefGoogle Scholar
  153. 153.
    Janik H, Marzec M. A review: fabrication of porous polyurethane scaffolds. Mater Sci Eng C Mater Biol Appl. 2015;48:586–91.PubMedCrossRefGoogle Scholar
  154. 154.
    Khan M, Xu Y, Hua S, Johnson J, Belevych A, Janssen PM, et al. Evaluation of changes in morphology and function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) cultured on an aligned-nanofiber cardiac patch. PLoS One. 2015;10:e0126338.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Sill TJ, von Recum HA. Electrospinning: applications in drug delivery and tissue engineering. Biomaterials. 2008;29:1989–2006.PubMedCrossRefGoogle Scholar
  156. 156.
    Guan J, Wang F, Li Z, Chen J, Guo X, Liao J, et al. The stimulation of the cardiac differentiation of mesenchymal stem cells in tissue constructs that mimic myocardium structure and biomechanics. Biomaterials. 2011;32:5568–80.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Xu Y, Patnaik S, Guo X, Li Z, Lo W, Butler R, et al. Cardiac differentiation of cardiosphere-derived cells in scaffolds mimicking morphology of the cardiac extracellular matrix. Acta Biomater. 2014;10:3449–62.PubMedCrossRefGoogle Scholar
  158. 158.
    Nag AC. Study of non-muscle cells of the adult mammalian heart: a fine structural analysis and distribution. Cytobios. 1980;28:41–61.PubMedGoogle Scholar
  159. 159.
    Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286–92.PubMedCrossRefGoogle Scholar
  160. 160.
    Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122:103–11.PubMedCrossRefGoogle Scholar
  161. 161.
    Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 1997;100:768–76.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Roberts AB, Russo A, Felici A, Flanders KC. Smad3: a key player in pathogenetic mechanisms dependent on TGF-β. Ann N Y Acad Sci. 2003;995:1–10.PubMedCrossRefGoogle Scholar
  163. 163.
    Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577–84.PubMedCrossRefGoogle Scholar
  164. 164.
    Leask A. Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res. 2015;116:1269–76.PubMedCrossRefGoogle Scholar
  165. 165.
    Willems IE, Havenith MG, De Mey JG, Daemen MJ. The alpha-smooth muscle actin-positive cells in healing human myocardial scars. Am J Pathol. 1994;145:868–75.PubMedPubMedCentralGoogle Scholar
  166. 166.
    Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med. 1994;1:71–81.PubMedPubMedCentralGoogle Scholar
  167. 167.
    Chesney J, Bucala R. Peripheral blood fibrocytes: novel fibroblast-like cells that present antigen and mediate tissue repair. Biochem Soc Trans. 1997;25:520–4.PubMedCrossRefGoogle Scholar
  168. 168.
    Mori L, Bellini A, Stacey MA, Schmidt M, Mattoli S. Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow. Exp Cell Res. 2005;304:81–90.PubMedCrossRefGoogle Scholar
  169. 169.
    Aiba S, Tagami H. Inverse correlation between CD34 expression and proline-4-hydroxylase immunoreactivity on spindle cells noted in hypertrophic scars and keloids. J Cutan Pathol. 1997;24:65–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 2003;112:1776–84.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Jain R, Shaul PW, Borok Z, Willis BC. Endothelin-1 induces alveolar epithelial-mesenchymal transition through endothelin type A receptor-mediated production of TGF-beta1. Am J Respir Cell Mol Biol. 2007;37:38–47.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Doerner AM, Zuraw BL. TGF-beta1 induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1beta but not abrogated by corticosteroids. Respir Res. 2009;10:1465–9921.CrossRefGoogle Scholar
  173. 173.
    Yamauchi Y, Kohyama T, Takizawa H, Kamitani S, Desaki M, Takami K, et al. Tumor necrosis factor-alpha enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-beta1. Exp Lung Res. 2010;36:12–24.PubMedCrossRefGoogle Scholar
  174. 174.
    Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 2007;13:952–61.PubMedCrossRefGoogle Scholar
  175. 175.
    Engebretsen KVT, Skårdal K, Bjørnstad S, Marstein HS, Skrbic B, Sjaastad I, et al. Attenuated development of cardiac fibrosis in left ventricular pressure overload by SM16, an orally active inhibitor of ALK5. J Mol Cell Cardiol. 2014;76:148–57.PubMedCrossRefGoogle Scholar
  176. 176.
    Tan SM, Zhang Y, Connelly KA, Gilbert RE, Kelly DJ. Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction. Am J Physiol Heart Circ Physiol. 2010;298:H1415–25.PubMedCrossRefGoogle Scholar
  177. 177.
    Campbell SE, Katwa LC. Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts. J Mol Cell Cardiol. 1997;29:1947–58.PubMedCrossRefGoogle Scholar
  178. 178.
    De Mello WC, Specht P. Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart. J Renin Angiotensin Aldosterone Syst. 2006;7:201–5.PubMedCrossRefGoogle Scholar
  179. 179.
    Shibasaki Y, Nishiue T, Masaki H, Tamura K, Matsumoto N, Mori Y, et al. Impact of the angiotensin II receptor antagonist, losartan, on myocardial fibrosis in patients with end-stage renal disease: assessment by ultrasonic integrated backscatter and biochemical markers. Hypertens Res. 2005;28:787–95.PubMedCrossRefGoogle Scholar
  180. 180.
    Ortiz LA, Lasky J, Gozal E, Ruiz V, Lungarella G, Cavarra E, et al. Tumor necrosis factor receptor deficiency alters matrix metalloproteinase 13/tissue inhibitor of metalloproteinase 1 expression in murine silicosis. Am J Respir Crit Care Med. 2001;163:244–52.PubMedCrossRefGoogle Scholar
  181. 181.
    Westermann D, Rutschow S, Van Linthout S, Linderer A, Bucker-Gartner C, Sobirey M, et al. Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus. Diabetologia. 2006;49:2507–13.PubMedCrossRefGoogle Scholar
  182. 182.
    Shukla MN, Rose JL, Ray R, Lathrop KL, Ray A, Ray P. Hepatocyte growth factor inhibits epithelial to myofibroblast transition in lung cells via Smad7. Am J Respir Cell Mol Biol. 2009;40:643–53.PubMedCrossRefGoogle Scholar
  183. 183.
    Mizuno S, Matsumoto K, Li MY, Nakamura T. HGF reduces advancing lung fibrosis in mice: a potential role for MMP-dependent myofibroblast apoptosis. Faseb J. 2005;19:580–2.PubMedGoogle Scholar
  184. 184.
    Singh S, Saraiva L, Elkington PT, Friedland JS. Regulation of matrix metalloproteinase-1, -3, and -9 in Mycobacterium tuberculosis-dependent respiratory networks by the rapamycin-sensitive PI3K/p70(S6K) cascade. Faseb J. 2014;28:85–93.PubMedCrossRefGoogle Scholar
  185. 185.
    Nakamura T, Matsumoto K, Mizuno S, Sawa Y, Matsuda H. Hepatocyte growth factor prevents tissue fibrosis, remodeling, and dysfunction in cardiomyopathic hamster hearts. Am J Physiol Heart Circ Physiol. 2005;288:H2131–9.PubMedCrossRefGoogle Scholar
  186. 186.
    Taniyama Y, Morishita R, Aoki M, Hiraoka K, Yamasaki K, Hashiya N, et al. Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy. Hypertension. 2002;40:47–53.PubMedCrossRefGoogle Scholar
  187. 187.
    Nakamura T, Sakai K, Matsumoto K. Hepatocyte growth factor twenty years on: much more than a growth factor. J Gastroenterol Hepatol. 2011;1:188–202.CrossRefGoogle Scholar
  188. 188.
    Ueda H, Nakamura T, Matsumoto K, Sawa Y, Matsuda H. A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats. Cardiovasc Res. 2001;51:41–50.PubMedCrossRefGoogle Scholar
  189. 189.
    Sakaguchi G, Tambara K, Sakakibara Y, Ozeki M, Yamamoto M, Premaratne G, et al. Control-released hepatocyte growth factor prevents the progression of heart failure in stroke-prone spontaneously hypertensive rats. Ann Thorac Surg. 2005;79:1627–34.PubMedCrossRefGoogle Scholar
  190. 190.
    Nakano J, Marui A, Muranaka H, Masumoto H, Noma H, Tabata Y, et al. Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin. Interact Cardiovasc Thorac Surg. 2014;18:300–7.PubMedCrossRefGoogle Scholar
  191. 191.
    Ren J, Samson WK, Sowers JR. Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease. J Mol Cell Cardiol. 1999;31:2049–61.PubMedCrossRefGoogle Scholar
  192. 192.
    Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, et al. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest. 1997;100:1991–9.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Conti E, Carrozza C, Capoluongo E, Volpe M, Crea F, Zuppi C, et al. Insulin-like growth factor-1 as a vascular protective factor. Circulation. 2004;110:2260–5.PubMedCrossRefGoogle Scholar
  194. 194.
    Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, 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;97:663–73.PubMedCrossRefGoogle Scholar
  195. 195.
    Ruvinov E, Leor J, Cohen S. The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction. Biomaterials. 2011;32:565–78.PubMedCrossRefGoogle Scholar
  196. 196.
    Suleiman MS, Singh RJR, Stewart CEH. Apoptosis and the cardiac action of insulin-like growth factor I. Pharmacol Ther. 2007;114:278–94.PubMedCrossRefGoogle Scholar
  197. 197.
    Ozawa CR, Banfi A, Glazer NL, Thurston G, Springer ML, Kraft PE, et al. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest. 2004;113:516–27.PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Salimath AS, Phelps EA, Boopathy AV, Che P-l, Brown M, García AJ, et al. Dual delivery of hepatocyte and vascular endothelial growth factors via a protease-degradable hydrogel improves cardiac function in rats. PLoS One. 2012;7:e50980.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Schwarz ER, Speakman MT, Patterson M, Hale SS, Isner JM, Kedes LH, et al. Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat – angiogenesis and angioma formation. J Am Coll Cardiol. 2000;35:1323–30.PubMedCrossRefGoogle Scholar
  200. 200.
    Kloner RA, Dow J, Chung G, Kedes LH. Intramyocardial injection of DNA encoding vascular endothelial growth factor in a myocardial infarction model. J Thromb Thrombolysis. 2000;10:285–9.PubMedCrossRefGoogle Scholar
  201. 201.
    Fan Z, Guan J. Antifibrotic therapies to control cardiac fibrosis. Biomater Res. 2016;20:13.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  • Zhaobo Fan
    • 1
  • Xiaofei Li
    • 1
  • Hong Niu
    • 1
  • Jianjun Guan
    • 1
    Email author
  1. 1.Department of Materials Science and EngineeringThe Ohio State UniversityColumbusUSA

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