Skip to main content
SpringerLink
Log in

Cellular Therapy for Ischemic Heart Disease: An Update

  • Chapter
  • First Online:
Stem Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1201))

Abstract

Ischemic heart disease (IHD), which includes heart failure (HF) induced by heart attack (myocardial infarction, MI), is a significant cause of morbidity and mortality worldwide (Benjamin, et al. Circulation 139:e56–e66, 2019). MI occurs at an alarmingly high rate in the United States (approx. One case every 40 seconds), and the failure to repair damaged myocardium is the leading cause of recurrent heart attacks, heart failure (HF), and death within 5 years of MI (Benjamin, et al. Circulation 139:e56–e66, 2019). At present, HF represents an unmet need with no approved clinical therapies to replace the damaged myocardium. As the population ages, the number of heart failure patients is projected to increase, doubling the annual cost by 2030 (Benjamin, et al. Circulation 139:e56–e66, 2019). In the past decades, stem cell therapy has become a promising strategy for cardiac regeneration. However, stem cell-based therapy yielded modest success in human clinical trials. This chapter examines the types of cells examined in cardiac therapy in the setting of IHD, with a brief introduction to ongoing research aiming at enhancing the therapeutic potential of transplanted cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Benjamin EJ et al (2019) Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 139:e56–e66. https://doi.org/10.1161/CIR.0000000000000659

    Article  PubMed  Google Scholar 

  2. Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856. https://doi.org/10.1038/nbt1117

    Article  CAS  PubMed  Google Scholar 

  3. Leong YY, Ng WH, Ellison-Hughes GM, Tan JJ (2017) Cardiac stem cells for myocardial regeneration: they are not alone. Front Cardiovasc Med 4:47. https://doi.org/10.3389/fcvm.2017.00047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813. https://doi.org/10.1038/385810a0

    Article  CAS  PubMed  Google Scholar 

  5. Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  6. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. https://doi.org/10.1016/j.cell.2006.07.024

    Article  CAS  PubMed  Google Scholar 

  7. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317. https://doi.org/10.1038/nature05934

    Article  CAS  PubMed  Google Scholar 

  8. Takahashi K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. https://doi.org/10.1016/j.cell.2007.11.019

    Article  CAS  PubMed  Google Scholar 

  9. Kattman SJ et al (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8:228–240. https://doi.org/10.1016/j.stem.2010.12.008

    Article  CAS  PubMed  Google Scholar 

  10. Cao N et al (2012) Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Res 22:219–236. https://doi.org/10.1038/cr.2011.195

    Article  CAS  PubMed  Google Scholar 

  11. Mohamed TM et al (2017) Chemical enhancement of in vitro and in vivo direct cardiac reprogramming. Circulation 135:978–995. https://doi.org/10.1161/CIRCULATIONAHA.116.024692

    Article  CAS  PubMed  Google Scholar 

  12. Mohamed TMA et al (2018) Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell 173:104–116.e112. https://doi.org/10.1016/j.cell.2018.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ieda M et al (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–386. https://doi.org/10.1016/j.cell.2010.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fu JD et al (2013) Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Rep 1:235–247. https://doi.org/10.1016/j.stemcr.2013.07.005

    Article  CAS  Google Scholar 

  15. Qian L, Berry EC, Fu JD, Ieda M, Srivastava D (2013) Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro. Nat Protoc 8:1204–1215. https://doi.org/10.1038/nprot.2013.067

    Article  CAS  PubMed  Google Scholar 

  16. Menasche P (2008) Skeletal myoblasts and cardiac repair. J Mol Cell Cardiol 45:545–553. https://doi.org/10.1016/j.yjmcc.2007.11.009

    Article  CAS  PubMed  Google Scholar 

  17. Roell W et al (2007) Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450:819–824. https://doi.org/10.1038/nature06321

    Article  CAS  PubMed  Google Scholar 

  18. Ghostine S et al (2002) Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation 106:I131–I136

    PubMed  Google Scholar 

  19. Cambria E et al (2017) Translational cardiac stem cell therapy: advancing from first-generation to next-generation cell types. NPJ Regen Med 2:17. https://doi.org/10.1038/s41536-017-0024-1

    Article  PubMed  PubMed Central  Google Scholar 

  20. Stock RA, Sindt MH, Parrott JC, Goedeken FK (1990) Effects of grain type, roughage level and monensin level on finishing cattle performance. J Anim Sci 68:3441–3455

    Article  CAS  PubMed  Google Scholar 

  21. Reinecke H, Poppa V, Murry CE (2002) Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. J Mol Cell Cardiol 34:241–249. https://doi.org/10.1006/jmcc.2001.1507

    Article  CAS  PubMed  Google Scholar 

  22. Gavira JJ et al (2010) Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. Eur Heart J 31:1013–1021. https://doi.org/10.1093/eurheartj/ehp342

    Article  PubMed  Google Scholar 

  23. Menasche P et al (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41:1078–1083

    Article  PubMed  Google Scholar 

  24. Menasche P et al (2008) The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117:1189–1200. https://doi.org/10.1161/CIRCULATIONAHA.107.734103

    Article  PubMed  Google Scholar 

  25. Hruban RH et al (1993) Fluorescence in situ hybridization for the Y-chromosome can be used to detect cells of recipient origin in allografted hearts following cardiac transplantation. Am J Pathol 142:975–980

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Laflamme MA, Myerson D, Saffitz JE, Murry CE (2002) Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ Res 90:634–640

    Article  CAS  PubMed  Google Scholar 

  27. Muller P et al (2002) Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation 106:31–35

    Article  PubMed  Google Scholar 

  28. Jackson KA et al (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107:1395–1402. https://doi.org/10.1172/JCI12150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Deb A et al (2003) Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation 107:1247–1249

    Article  PubMed  Google Scholar 

  30. Sanganalmath SK, Bolli R (2013) Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res 113:810–834. https://doi.org/10.1161/CIRCRESAHA.113.300219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vrtovec B, Bolli R (2019) Potential strategies for clinical translation of repeated cell therapy. Circ Res 124:690–692. https://doi.org/10.1161/CIRCRESAHA.118.314653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen CH, Sereti KI, Wu BM, Ardehali R (2015) Translational aspects of cardiac cell therapy. J Cell Mol Med 19:1757–1772. https://doi.org/10.1111/jcmm.12632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bel A et al (2003) Transplantation of autologous fresh bone marrow into infarcted myocardium: a word of caution. Circulation 108(Suppl 1):II247–II252. https://doi.org/10.1161/01.cir.0000089040.11131.d4

    Article  PubMed  Google Scholar 

  34. de Silva R et al (2008) Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction. Eur Heart J 29:1772–1782. https://doi.org/10.1093/eurheartj/ehn216

    Article  CAS  PubMed  Google Scholar 

  35. Moelker AD et al (2006) Reduction in infarct size, but no functional improvement after bone marrow cell administration in a porcine model of reperfused myocardial infarction. Eur Heart J 27:3057–3064. https://doi.org/10.1093/eurheartj/ehl401

    Article  PubMed  Google Scholar 

  36. Graham JJ et al (2010) Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI. Am J Physiol Heart Circ Physiol 299:H125–H133. https://doi.org/10.1152/ajpheart.01260.2008

    Article  CAS  PubMed  Google Scholar 

  37. Orlic D et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705. https://doi.org/10.1038/35070587

    Article  CAS  PubMed  Google Scholar 

  38. Meyer GP et al (2006) Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 113:1287–1294. https://doi.org/10.1161/CIRCULATIONAHA.105.575118

    Article  PubMed  Google Scholar 

  39. Schachinger V et al (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221. https://doi.org/10.1056/NEJMoa060186

    Article  CAS  PubMed  Google Scholar 

  40. Traverse JH et al (2012) Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA 308:2380–2389. https://doi.org/10.1001/jama.2012.28726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Surder D et al (2013) Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function. Circulation 127:1968–1979. https://doi.org/10.1161/CIRCULATIONAHA.112.001035

    Article  PubMed  Google Scholar 

  42. Perin EC et al (2012) Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA 307:1717–1726. https://doi.org/10.1001/jama.2012.418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Assmus B et al (2016) Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT. Eur Heart J 37:1659–1666. https://doi.org/10.1093/eurheartj/ehv559

    Article  PubMed  Google Scholar 

  44. Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of Guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    CAS  PubMed  Google Scholar 

  45. Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317. https://doi.org/10.1080/14653240600855905

    Article  CAS  PubMed  Google Scholar 

  46. Caplan AI (2009) Why are MSCs therapeutic? New data: new insight. J Pathol 217:318–324. https://doi.org/10.1002/path.2469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hass R, Kasper C, Bohm S, Jacobs R (2011) Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 9:12. https://doi.org/10.1186/1478-811X-9-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yin JQ, Zhu J, Ankrum JA (2019) Manufacturing of primed mesenchymal stromal cells for therapy. Nat Biomed Eng 3:90–104. https://doi.org/10.1038/s41551-018-0325-8

    Article  CAS  PubMed  Google Scholar 

  49. Murray IR et al (2014) Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci 71:1353–1374. https://doi.org/10.1007/s00018-013-1462-6

    Article  CAS  PubMed  Google Scholar 

  50. Crisan M et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313. https://doi.org/10.1016/j.stem.2008.07.003

    Article  CAS  PubMed  Google Scholar 

  51. Davies JE, Walker JT, Keating A (2017) Concise review: Wharton’s jelly: the rich, but enigmatic, source of Mesenchymal Stromal. Cells Stem Cells Transl Med 6:1620–1630. https://doi.org/10.1002/sctm.16-0492

    Article  PubMed  PubMed Central  Google Scholar 

  52. Zuk PA et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228. https://doi.org/10.1089/107632701300062859

    Article  CAS  PubMed  Google Scholar 

  53. Karantalis V, Hare JM (2015) Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res 116:1413–1430. https://doi.org/10.1161/CIRCRESAHA.116.303614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bartolucci J et al (2017) Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1/2 randomized controlled trial (RIMECARD trial [randomized clinical trial of intravenous infusion umbilical cord mesenchymal stem cells on cardiopathy]). Circ Res 121:1192–1204. https://doi.org/10.1161/CIRCRESAHA.117.310712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Wang HS et al (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337. https://doi.org/10.1634/stemcells.2004-0013

    Article  PubMed  Google Scholar 

  56. Musialek P et al (2015) Myocardial regeneration strategy using Wharton’s jelly mesenchymal stem cells as an off-the-shelf ‘unlimited’ therapeutic agent: results from the Acute Myocardial Infarction First-in-Man Study. Postepy Kardiol Interwencyjnej 11:100–107. https://doi.org/10.5114/pwki.2015.52282

    Article  PubMed  PubMed Central  Google Scholar 

  57. Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242

    Article  CAS  PubMed  Google Scholar 

  58. Gao LR et al (2015) Intracoronary infusion of Wharton’s jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial. BMC Med 13:162. https://doi.org/10.1186/s12916-015-0399-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lohan P et al (2014) Changes in immunological profile of allogeneic mesenchymal stem cells after differentiation: should we be concerned? Stem Cell Res Ther 5:99. https://doi.org/10.1186/scrt488

    Article  PubMed  PubMed Central  Google Scholar 

  60. Ankrum JA, Ong JF, Karp JM (2014) Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 32:252–260. https://doi.org/10.1038/nbt.2816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hashemi SM et al (2008) A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction. Eur Heart J 29:251–259. https://doi.org/10.1093/eurheartj/ehm559

    Article  PubMed  Google Scholar 

  62. Gyongyosi M et al (2008) Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging 1:94–103. https://doi.org/10.1161/CIRCIMAGING.108.797449

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dixon JA et al (2009) Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction. Circulation 120:S220–S229. https://doi.org/10.1161/CIRCULATIONAHA.108.842302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Quevedo HC et al (2009) Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci U S A 106:14022–14027. https://doi.org/10.1073/pnas.0903201106

    Article  PubMed  PubMed Central  Google Scholar 

  65. Hatzistergos KE et al (2010) Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res 107:913–922. https://doi.org/10.1161/CIRCRESAHA.110.222703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Williams AR et al (2013) Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J Am Heart Assoc 2:e000140. https://doi.org/10.1161/JAHA.113.000140

    Article  PubMed  PubMed Central  Google Scholar 

  67. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93–98

    Article  PubMed  Google Scholar 

  68. Makino S et al (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:697–705. https://doi.org/10.1172/JCI5298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Szaraz P, Gratch YS, Iqbal F, Librach CL (2017) In vitro differentiation of human mesenchymal stem cells into functional cardiomyocyte-like cells. J Vis Exp. https://doi.org/10.3791/55757

  70. Martin-Rendon E et al (2008) 5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies. Vox Sang 95:137–148. https://doi.org/10.1111/j.1423-0410.2008.01076.x

    Article  CAS  PubMed  Google Scholar 

  71. Hamid T, Prabhu SD (2017) Immunomodulation is the key to cardiac repair. Circ Res 120:1530–1532. https://doi.org/10.1161/CIRCRESAHA.117.310954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ohnishi S et al (2007) Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J Mol Cell Cardiol 42:88–97. https://doi.org/10.1016/j.yjmcc.2006.10.003

    Article  CAS  PubMed  Google Scholar 

  73. Amado LC et al (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 102:11474–11479. https://doi.org/10.1073/pnas.0504388102

    Article  CAS  Google Scholar 

  74. Silva GV et al (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156. https://doi.org/10.1161/01.CIR.0000151812.86142.45

    Article  CAS  PubMed  Google Scholar 

  75. Mirotsou M et al (2007) 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 U S A 104:1643–1648. https://doi.org/10.1073/pnas.0610024104

    Article  CAS  Google Scholar 

  76. Lai RC et al (2010) Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 4:214–222. https://doi.org/10.1016/j.scr.2009.12.003

    Article  CAS  PubMed  Google Scholar 

  77. Schuleri KH et al (2009) Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J 30:2722–2732. https://doi.org/10.1093/eurheartj/ehp265

    Article  PubMed  PubMed Central  Google Scholar 

  78. Amado LC et al (2006) Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol 48:2116–2124. https://doi.org/10.1016/j.jacc.2006.06.073

    Article  PubMed  Google Scholar 

  79. Hare JM et al (2009) 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 54:2277–2286. https://doi.org/10.1016/j.jacc.2009.06.055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rodrigo SF et al (2013) Intramyocardial injection of autologous bone marrow-derived ex vivo expanded mesenchymal stem cells in acute myocardial infarction patients is feasible and safe up to 5 years of follow-up. J Cardiovasc Transl Res 6:816–825. https://doi.org/10.1007/s12265-013-9507-7

    Article  PubMed  PubMed Central  Google Scholar 

  81. Houtgraaf JH et al (2012) First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 59:539–540. https://doi.org/10.1016/j.jacc.2011.09.065

    Article  PubMed  Google Scholar 

  82. Hare JM et al (2012) Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308:2369–2379. https://doi.org/10.1001/jama.2012.25321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Heldman AW et al (2014) Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA 311:62–73. https://doi.org/10.1001/jama.2013.282909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Mathiasen AB et al (2015) Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial). Eur Heart J 36:1744–1753. https://doi.org/10.1093/eurheartj/ehv136

    Article  CAS  PubMed  Google Scholar 

  85. Bartunek J et al (2013) Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol 61:2329–2338. https://doi.org/10.1016/j.jacc.2013.02.071

    Article  PubMed  Google Scholar 

  86. Behfar A et al (2010) Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol 56:721–734. https://doi.org/10.1016/j.jacc.2010.03.066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Teerlink JR et al (2017) Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) study. Eur J Heart Fail 19:1520–1529. https://doi.org/10.1002/ejhf.898

    Article  PubMed  Google Scholar 

  88. Tompkins BA, Rieger AC, Florea V, Banerjee MN, Hare JM (2017) New insights into cell-based therapy for heart failure from the CHART-1 study. Eur J Heart Fail 19:1530–1533. https://doi.org/10.1002/ejhf.955

    Article  PubMed  Google Scholar 

  89. Lunde K et al (2006) Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 355:1199–1209. https://doi.org/10.1056/NEJMoa055706

    Article  CAS  Google Scholar 

  90. Jeevanantham V et al (2012) Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation 126:551–568. https://doi.org/10.1161/CIRCULATIONAHA.111.086074

    Article  PubMed  PubMed Central  Google Scholar 

  91. Afzal MR et al (2015) Adult bone marrow cell therapy for ischemic heart disease: evidence and insights from randomized controlled trials. Circ Res 117:558–575. https://doi.org/10.1161/CIRCRESAHA.114.304792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Abdel-Latif A et al (2007) Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 167:989–997. https://doi.org/10.1001/archinte.167.10.989

    Article  PubMed  Google Scholar 

  93. Zampetaki A, Kirton JP, Xu Q (2008) Vascular repair by endothelial progenitor cells. Cardiovasc Res 78:413–421. https://doi.org/10.1093/cvr/cvn081

    Article  CAS  PubMed  Google Scholar 

  94. Asahara T et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  CAS  PubMed  Google Scholar 

  95. Medina RJ et al (2017) Endothelial progenitors: a consensus statement on nomenclature. Stem Cells Transl Med 6:1316–1320. https://doi.org/10.1002/sctm.16-0360

    Article  PubMed  PubMed Central  Google Scholar 

  96. Asahara T, Kawamoto A, Masuda H (2011) Concise review: circulating endothelial progenitor cells for vascular medicine. Stem Cells 29:1650–1655. https://doi.org/10.1002/stem.745

    Article  CAS  PubMed  Google Scholar 

  97. Ambasta RK, Kohli H, Kumar P (2017) Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder. J Transl Med 15:185. https://doi.org/10.1186/s12967-017-1280-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bianconi V et al (2018) Endothelial and cardiac progenitor cells for cardiovascular repair: a controversial paradigm in cell therapy. Pharmacol Ther 181:156–168. https://doi.org/10.1016/j.pharmthera.2017.08.004

    Article  CAS  Google Scholar 

  99. Kalka C et al (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 97:3422–3427. https://doi.org/10.1073/pnas.070046397

  100. Kawamoto A et al (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103:634–637

    Article  CAS  PubMed  Google Scholar 

  101. Losordo DW et al (2011) Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 109:428–436. https://doi.org/10.1161/CIRCRESAHA.111.245993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li R, Li XM, Chen JR (2016) Clinical efficacy and safety of autologous stem cell transplantation for patients with ST-segment elevation myocardial infarction. Ther Clin Risk Manag 12:1171–1189. https://doi.org/10.2147/TCRM.S107199

    Article  PubMed  Google Scholar 

  103. Velagapudi P et al (2019) Intramyocardial autologous CD34+ cell therapy for refractory angina: a meta-analysis of randomized controlled trials. Cardiovasc Revasc Med 20:215–219. https://doi.org/10.1016/j.carrev.2018.05.018

    Article  PubMed  Google Scholar 

  104. Schachinger V et al (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 44:1690–1699. https://doi.org/10.1016/j.jacc.2004.08.014

    Article  PubMed  Google Scholar 

  105. Hashimoto H, Olson EN, Bassel-Duby R (2018) Therapeutic approaches for cardiac regeneration and repair. Nat Rev Cardiol 15:585–600. https://doi.org/10.1038/s41569-018-0036-6

    Article  PubMed  PubMed Central  Google Scholar 

  106. Oh H et al (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 100:12313–12318. https://doi.org/10.1073/pnas.2132126100

    Article  CAS  Google Scholar 

  107. Laugwitz KL et al (2005) Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433:647–653. https://doi.org/10.1038/nature03215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Messina E et al (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921. https://doi.org/10.1161/01.RES.0000147315.71699.51

    Article  CAS  PubMed  Google Scholar 

  109. The Lancet, E. Expression of concern: the SCIPIO trial. Lancet 383:1279. https://doi.org/10.1016/S0140-6736(14)60608-5

    Article  CAS  Google Scholar 

  110. Davis DR et al (2009) Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue. PLoS One 4:e7195. https://doi.org/10.1371/journal.pone.0007195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Smith RR et al (2007) Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115:896–908. https://doi.org/10.1161/CIRCULATIONAHA.106.655209

    Article  PubMed  CAS  Google Scholar 

  112. Johnston PV et al (2009) Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation 120:1075–1083, 1077 p following 1083. https://doi.org/10.1161/CIRCULATIONAHA.108.816058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Chimenti I et al (2010) Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res 106:971–980. https://doi.org/10.1161/CIRCRESAHA.109.210682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Zwetsloot PP et al (2016) Cardiac stem cell treatment in myocardial infarction: a systematic review and meta-analysis of preclinical studies. Circ Res 118:1223–1232. https://doi.org/10.1161/CIRCRESAHA.115.307676

    Article  CAS  PubMed  Google Scholar 

  115. Makkar RR et al (2012) Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379:895–904. https://doi.org/10.1016/S0140-6736(12)60195-0

    Article  Google Scholar 

  116. Malliaras K et al (2014) Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol 63:110–122. doi:https://doi.org/10.1016/j.jacc.2013.08.724

    Article  PubMed  Google Scholar 

  117. Williams AR et al (2013) 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 127:213–223. https://doi.org/10.1161/CIRCULATIONAHA.112.131110

    Article  PubMed  Google Scholar 

  118. Karantalis V et al (2015) Synergistic effects of combined cell therapy for chronic ischemic cardiomyopathy. J Am Coll Cardiol 66:1990–1999. https://doi.org/10.1016/j.jacc.2015.08.879

    Article  PubMed  PubMed Central  Google Scholar 

  119. Qian L et al (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485:593–598. doi:https://doi.org/10.1038/nature11044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Li XH et al (2015) Generation of functional human cardiac progenitor cells by high-efficiency protein transduction. Stem Cells Transl Med 4:1415–1424. https://doi.org/10.5966/sctm.2015-0136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lee K et al (2015) Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells. Int J Nanomedicine 10:1841–1854. https://doi.org/10.2147/IJN.S75124

  122. Bergmann O et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324, 98–102, doi:https://doi.org/10.1126/science.1164680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Senyo SE et al (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493:433–436. https://doi.org/10.1038/nature11682

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Ali SR et al (2014) Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice. Proc Natl Acad Sci U S A 111:8850–8855. https://doi.org/10.1073/pnas.1408233111

    Article  CAS  Google Scholar 

  125. Walsh S, Ponten A, Fleischmann BK, Jovinge S (2010) Cardiomyocyte cell cycle control and growth estimation in vivo–an analysis based on cardiomyocyte nuclei. Cardiovasc Res 86:365–373. https://doi.org/10.1093/cvr/cvq005

    Article  CAS  PubMed  Google Scholar 

  126. Cai CL, Molkentin JD (2017) The elusive progenitor cell in cardiac regeneration: Slip Slidin’ away. Circ Res 120:400–406. https://doi.org/10.1161/CIRCRESAHA.116.309710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Mollova M et al (2013) Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U S A 110:1446–1451. https://doi.org/10.1073/pnas.1214608110

    Article  CAS  Google Scholar 

  128. Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190. https://doi.org/10.1126/science.1077857

    Article  CAS  PubMed  Google Scholar 

  129. Heallen T et al (2013) Hippo signaling impedes adult heart regeneration. Development 140:4683–4690. https://doi.org/10.1242/dev.102798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Xin M et al (2013) Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci U S A 110:13839–13844. https://doi.org/10.1073/pnas.1313192110

    Article  CAS  Google Scholar 

  131. Leach JP et al (2017) Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 550:260–264. https://doi.org/10.1038/nature24045

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Cheng RK et al (2007) Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents heart failure. Circ Res 100:1741–1748. https://doi.org/10.1161/CIRCRESAHA.107.153544

    Article  CAS  PubMed  Google Scholar 

  133. Shapiro SD et al (2014) Cyclin A2 induces cardiac regeneration after myocardial infarction through cytokinesis of adult cardiomyocytes. Sci Transl Med 6:224ra227. https://doi.org/10.1126/scitranslmed.3007668

    Article  PubMed  CAS  Google Scholar 

  134. Woo YJ et al (2006) Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure. Circulation 114:I206–213. https://doi.org/10.1161/CIRCULATIONAHA.105.000455

    Article  CAS  Google Scholar 

  135. Hastings CL et al (2015) Drug and cell delivery for cardiac regeneration. Adv Drug Deliv Rev 84:85–106. https://doi.org/10.1016/j.addr.2014.08.006

    Article  CAS  PubMed  Google Scholar 

  136. Weinberger F, Mannhardt I, Eschenhagen T (2017) Engineering cardiac muscle tissue: a maturating field of research. Circ Res 120:1487–1500. https://doi.org/10.1161/CIRCRESAHA.117.310738

    Article  CAS  PubMed  Google Scholar 

  137. Ogle BM et al (2016) Distilling complexity to advance cardiac tissue engineering. Sci Transl Med 8:342ps313. https://doi.org/10.1126/scitranslmed.aad2304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Emmert MY et al. (2013) Human stem cell-based three-dimensional microtissues for advanced cardiac cell therapies. Biomaterials 34:6339–6354. https://doi.org/10.1016/j.biomaterials.2013.04.034

    Article  CAS  PubMed  Google Scholar 

  139. Ovsianikov A, Khademhosseini A, Mironov V (2018) The synergy of scaffold-based and scaffold-free tissue engineering strategies. Trends Biotechnol 36:348–357. https://doi.org/10.1016/j.tibtech.2018.01.005

    Article  CAS  PubMed  Google Scholar 

  140. Zhao TC et al (2008) Targeting human CD34+ hematopoietic stem cells with anti-CD45 x anti-myosin light-chain bispecific antibody preserves cardiac function in myocardial infarction. J Appl Physiol (1985) 104:1793–1800. https://doi.org/10.1152/japplphysiol.01109.2007

    Article  PubMed  Google Scholar 

  141. Zahid M et al (2018) Cardiac targeting peptide, a novel cardiac vector: studies in bio-distribution, imaging application, and mechanism of transduction. Biomolecules 8. https://doi.org/10.3390/biom8040147

    Article  PubMed Central  CAS  Google Scholar 

  142. Kim H et al (2018) Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes. Biochem Biophys Res Commun 499:803–808. https://doi.org/10.1016/j.bbrc.2018.03.227

    Article  CAS  PubMed  Google Scholar 

  143. Shin M et al (2018) Targeting protein and peptide therapeutics to the heart via tannic acid modification. Nat Biomed Eng 2:304–317. https://doi.org/10.1038/s41551-018-0227-9

    Article  CAS  PubMed  Google Scholar 

  144. Tang YL et al (2009) Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res 104:1209–1216. https://doi.org/10.1161/CIRCRESAHA.109.197723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Bolli R Repeated cell therapy: a paradigm shift whose time has come. Circ Res 120:1072–1074. https://doi.org/10.1161/CIRCRESAHA.117.310710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Tokita Y et al (2016) Repeated administrations of cardiac progenitor cells are markedly more effective than a single administration: a new paradigm in cell therapy. Circ Res 119:635–651. https://doi.org/10.1161/CIRCRESAHA.116.308937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Saha Cardiovascular Research Center and Department of Pharmacology, University of Kentucky, Lexington, KY, USA

    Hsuan Peng

  2. Gill Heart and Vascular Institute and Division of Cardiovascular Medicine, University of Kentucky and the Lexington VA Medical Center, Lexington, KY, USA

    Ahmed Abdel-Latif

Authors
  1. Hsuan Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmed Abdel-Latif
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed Abdel-Latif .

Editor information

Editors and Affiliations

  1. Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    Mariusz Z. Ratajczak

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Peng, H., Abdel-Latif, A. (2019). Cellular Therapy for Ischemic Heart Disease: An Update. In: Ratajczak, M. (eds) Stem Cells. Advances in Experimental Medicine and Biology, vol 1201. Springer, Cham. https://doi.org/10.1007/978-3-030-31206-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation