Cardiac Stem Cells for Myocardial Regeneration: They Are Not Alone

Frontiers in Cardiovascular Medicine

Volumn 4, Issue , 2017, Pages

  Leong, Yin Yee ^a   Ng, Wai Hoe ^a   Ellison Hughes, Georgina M ^b,c   Tan, Jun Jie ^a,b,c  

^a ADVANCED MEDICAL AND DENTAL INSTITUTE   (Malaysia)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

cardiac stem and progenitor cells; cardiac tissue engineering; cell therapy; interactions; myocardial regeneration; synergy

Indexed keywords

EID: 85038870432     PISSN: None     EISSN: 2297055X     Source Type: Journal    
DOI: 10.3389/fcvm.2017.00047     Document Type: Review

References (114)

1. World Health Organisation. Global Status Report on Noncommunicable Disease. WHO Press (2014).
2. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Circulation (2007) 116:2634–53.10.1161/CIRCULATIONAHA.107.187397
3. Minicucci MF, Azevedo PS, Polegato BF, Paiva SAR, Zornoff LAM. Heart failure after myocardial infarction: clinical implications and treatment. Clin Cardiol (2011) 34(7):410–4.10.1002/clc.2092221688276
4. Sutton MGSJ, Sharpe N. Left ventricular remodeling after myocardial infarction pathophysiology and therapy. Circulation (2000) 101:2981–8.10.1161/01.CIR.101.25.2981
5. Deb A, Wang S, Skelding KA, Miller D, Simper D, Caplice NM. Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation (2003) 107(9):1247–9.10.1161/01.CIR.0000061910.39145.F012628942
6. Laflamme MA, Myerson D, Saffitz JE, Murry CE. Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ Res (2002) 90(6):634–40.10.1161/01.RES.0000014822.62629.EB11934829
7. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, et al. Chimerism of the transplanted heart. N Engl J Med (2002) 346(1):5–15.10.1056/NEJMoa012081
8. Behfar A, Crespo-Diaz R, Terzic A, Gersh BJ. Cell therapy for cardiac repair-lessons from clinical trials. Nat Rev Cardiol (2014) 11(4):232–46.10.1038/nrcardio.2014.9
9. Fujii H, Tomita S, Nakatani T, Fukuhara S, Hanatani A, Ohtsu Y, et al. A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model. J Am Coll Cardiol (2004) 43(7):1299–305.10.1016/j.jacc.2003.09.06115063445
10. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res (1999) 85(3):221–8.10.1161/01.RES.85.3.22110436164
11. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone marrow cells regenerate infarcted myocardium. Nature (2001) 410(6829):701–5.10.1038/3507058711287958
12. Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature (2004) 428(6983):664–8.10.1038/nature0244615034593
13. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature (2004) 428(6983):668–73.10.1038/nature0246015034594
14. Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation (2002) 206:3009–17.10.1161/01.CIR.0000043246.74879.CD
15. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI trial. J Am Coll Cardiol (2004) 44(8):1690–9.10.1016/j.jacc.2004.08.01415489105
16. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet (2004) 364:141–8.10.1016/S0140-6736(04)16626-9
17. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, et al. Intracoronary bone marrow cell transfer after myocardial infarction. Circulation (2006) 113:1287–94.10.1161/CIRCULATIONAHA.105.575118
18. Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med (2006) 355:1210–21.10.1056/NEJMoa060186
19. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet (2006) 367:113–21.10.1016/S0140-6736(05)67861-016413875
20. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med (2006) 355(12):1199–209.10.1056/NEJMoa05570616990383
21. Ge J, Li Y, Qian J, Shi J, Wang Q, Niu Y, et al. Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart (2006) 92:1764–7.10.1136/hrt.2005.085431
22. Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, et al. Transcoronary transplantation of functionally competent BMCS is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure. Circ Res (2007) 100:1234–41.10.1161/01.RES.0000264508.47717.6b
23. Gowdak LH, Schettert IT, Baptista E, Lopes NL, Rochitte CE, Vieira ML, et al. Intramyocardial injection of autologous bone marrow cells as an adjunctive therapy to incomplete myocardial revascularization – safety issues. Clinics (2008) 63(2):207–14.10.1590/S1807-59322008000200009
24. Huikuri HV, Kervinen K, Niemela M, Ylitalo K, Säily M, Koistinen P, et al. Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. Eur Heart J (2008) 29(22):2723–32.10.1093/eurheartj/ehn436
25. Hirsch A, Nijveldt R, van der Vleuten PA, Tio RA, van der Giessen WJ, Marques KMJ, et al. Intracoronary infusion of autologous mononuclear bone marrow cells in patients with acute myocardial infarction treated with primary PCI: pilot study of the multicenter HEBE trial. Catheter Cardiovasc Interv (2008) 71:273–81.10.1002/ccd.2133718288734
26. Meyer GP, Wollert KC, Lotz J, Pirr J, Rager U, Lippolt P, et al. Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial. Eur Heart J (2009) 30(24):2978–84.10.1093/eurheartj/ehp37419773226
27. Beitnes JO, Hopp E, Lunde K, Solheim S, Arnesen H, Brinchmann JE, et al. Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study. Heart (2009) 95:1983–9.10.1136/hrt.2009.17891319833610
28. + cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre myocardial regeneration by intracoronary infusion of selected population of stem cells in acute myocardial infarction (REGENT) trial. Eur Heart J (2009) 30:1313–21.10.1093/eurheartj/ehp07319208649
29. 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(3):428–34.10.1016/j.ahj.2010.06.00920826249
30. Roncalli J, Mouquet F, Piot C, Trochu J-N, Corvoisier PL, Neuder Y, et al. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial. Eur Heart J (2011) 32:1748–57.10.1093/eurheartj/ehq45521127322
31. Assmus B, Rolf A, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, et al. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail (2010) 3(1):89–96.10.1161/circheartfailure.108.84324319996415
32. Perin EC, Silva GV, Henry TD, Cabreira-Hansen MG, Moore WH, Coulter SA, et al. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J (2011) 161(6):1078.e–87.e.10.1016/j.ahj.2011.01.02821641354
33. Hirsch A, Nijveldt R, van der Vleuten PA, Tijssen JGP, van der Giessen WJ, Tio RA, et al. Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial. Eur Heart J (2011) 32:1736–47.10.1093/eurheartj/ehq44921148540
34. Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DXM, et al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the late TIME randomized trial. JAMA (2011) 306(19):2110–9.10.1001/jama.2011.1670
35. Leistner DM, Fischer-Rasokat U, Honold J, Seeger FH, Schachinger V, Lehmann R, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy. Clin Res Cardiol (2011) 100(10):925–34.10.1007/s00392-011-0327-y21633921
36. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DXM, Ellis SG, et al. 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 (2012) 308(22):2380–9.10.1001/jama.2012.2872623129008
37. Antonitsis P, Anastasiadis K, Koliakos G, Vaitsopoulou C, Kouzi-Koliakou K, Doumas A, et al. Intramyocardial implantation of autologous bone marrow-derived stem cells combined with coronary artery bypass grafting in patients with ischemic cardiomyopathy: a pilot study. Hippokratia (2012) 16(4):366–70.23935319
38. Perin EC, Willerson JT, Pepine CJ, Henry TD, Ellisy SG, Zhao DXM, et al. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure. JAMA (2012) 307(16):1717–26.10.1001/jama.2012.418
39. Surder D, Manka R, Lo Cicero V, Moccetti T, Rufibach K, Soncin S, et al. Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function. Circulation (2013) 127(19):1968–79.10.1161/circulationaha.112.00103523596006
40. van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin S-CJ, et al. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature (2014) 509(7500):337–41.10.1038/nature1330924805242
41. Sultana N, Zhang L, Yan J, Chen J, Cai W, Razzaque S, et al. Resident c-kit(+) cells in the heart are not cardiac stem cells. Nat Commun (2015) 6:8701.10.1038/ncomms9701
42. Liu Q, Yang R, Huang X, Zhang H, He L, Zhang L, et al. Genetic lineage tracing identifies in situ kit-expressing cardiomyocytes. Cell Res (2016) 26(1):119–30.10.1038/cr.2015.14326634606
43. Nadal-Ginard B, Ellison GM, Torella D. Absence of evidence is not evidence of absence: pitfalls of cre knock-ins in the c-kit locus. Circ Res (2014) 115(4):415–8.10.1161/circresaha.114.304676
44. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy (2006) 8(4):315–7.10.1080/1465324060085590516923606
45. Schu S, Nosov M, Flynn LO, Shaw G, Treacy O, Barry F, et al. Immunogenicity of allogeneic mesenchymal stem cells. J Cell Mol Med (2012) 16(9):2094–103.10.1111/j.1582-4934.2011.01509.x
46. Amado LC, Saliaris AP, Schuleri KH, St. John M, Xie J-S, Cattaneo S, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A (2005) 102(32):11474–9.10.1073/pnas.050438810216061805
47. Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res (2011) 109:923–40.10.1161/CIRCRESAHA.111.24314721960725
48. Ye N-S, Zhang R-L, Zhao Y-F, Feng X, Wang Y-M, Luo G-A. Effect of 5-azacytidine on the protein expression of porcine bone marrow mesenchymal stem cells in vitro. Geno Prot Bioinfo (2006) 4(1):18–25.10.1016/S1672-0229(06)60012-016689698
49. Antonitsis P, Ioannidou-Papagiannaki E, Kaidoglou A, Papakonstantinou C. In vitro cardiomyogenic differentiation of adult human bone marrow mesenchymal stem cells. The role of 5-azacytidine. Interact Cardiovasc Thorac Surg (2007) 6:593–7.10.1510/icvts.2007.15787517670726
50. Li X, Yu X, Lin Q, Deng C, Shan Z, Yang M, et al. Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment. J Mol Cell Cardiol (2007) 42:295–303.10.1016/j.yjmcc.2006.07.00216919679
51. Xu W, Zhang X, Qian H, Zhu W, Sun X, Hu J, et al. Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro. Exp Biol Med (2004) 229(7):623–31.10.1177/15353702042290070615229356
52. Martin-Rendon E, Sweeney D, Lu F, Girdlestone J, Navarrete C, Watt SM. 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 (2008) 95:137–48.10.1111/j.1423-0410.2008.01076.x18557828
53. Rose RA, Jiang H, Wang X, Helke S, Tsoporis JN, Gong N, et al. Bone marrow-derived mesenchymal stromal cells express cardiac-specific markers, retain the stromal phenotype, and do not become functional cardiomyocytes in vitro. Stem Cells (2008) 329:2884–92.10.1634/stemcells.2008-0329
54. Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, et al. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation: novelty and significance. Circ Res (2010) 107:913–22.10.1161/circresaha.110.222703
55. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signalling and therapy. Circ Res (2008) 103:1204–19.10.1161/circresaha.108.176826
56. Hare JM, Fishman JE, Gerstenblith G, Velazquez DLD, Zambrano JP, Suncion VY, et al. Comparison of allogeneic vs autologous bonemarrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA (2012) 308(22):2369–79.10.1001/jama.2012.25321
57. Mathiasen AB, Qayyum AA, Jørgensen E, Helqvist S, Fischer-Nielsen A, Kofoed KF, et al. 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 (2015) 36(27):1744–53.10.1093/eurheartj/ehv13625926562
58. Guijarro D, Lebrin M, Lairez O, Bourin P, Piriou N, Pozzo J, et al. Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: results of the MESAMI 1 pilot trial. Int J Cardiol (2016) 209:258–65.10.1016/j.ijcard.2016.02.01626901787
59. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol (2004) 94(1):92–5.10.1016/j.amjcard.2004.03.03415219514
60. 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(24):2277–86.10.1016/j.jacc.2009.06.05519958962
61. Karantalis V, DiFede DL, Gerstenblith G, Pham S, Symes J, Zambrano JP, et al. Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: the prospective randomized study of mesenchymal stem cell therapy in patients undergoing cardiac surgery (PROMETHEUS) trial. Circ Res (2014) 114:1302–10.10.1161/circresaha.114.30318024565698
62. Lee JW, Lee SH, Youn YJ, Ahn MS, Kim JY, Yoo BS, et al. A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction. J Korean Med Sci (2014) 29(1):23–31.10.3346/jkms.2014.29.1.2324431901
63. Heldman AW, DiFede DL, Fishman JE, Zambrano JP, Trachtenberg BH, Karantalis V, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA (2014) 311(1):62–73.10.1001/jama.2013.282909
64. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell (2003) 114:763–76.10.1016/S0092-8674(03)00687-1
65. Messina E, Angelis LD, Frati G, Morrone S, Chimenti S, Fiordaliso F, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res (2004) 95:911–21.10.1161/01.res.0000147315.71699.5115472116
66. Nadal-Ginard B, Ellison GM, Torella D. The cardiac stem cell compartment is indispensable for myocardial cell homeostasis, repair and regeneration in the adult. Stem Cell Res (2014) 13:615–30.10.1016/j.scr.2014.04.00824838077
67. Smith AJ, Lewis FC, Aquila I, Waring CD, Nocera A, Agosti V, et al. Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart. Nat Protoc (2014) 9(7):1662–81.10.1038/nprot.2014.11324945383
68. Miyamoto S, Kawaguchi N, Ellison GM, Matsuoka R, Shin’oka T, Kurosawa H. Characterization of long-term cultured c-kit+ cardiac stem cells derived from adult rat hearts. Stem Cells Dev (2010) 19(1):105–16.10.1089/scd.2009.004119580375
69. Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, et al. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell (2013) 154:827–42.10.1016/j.cell.2013.07.03923953114
70. Hong KU, Guo Y, Li Q-H, Cao P, Al-Maqtari T, Vajravelu BN, et al. C-kit+ cardiac stem cells alleviate post-myocardial infarction left ventricular dysfunction despite poor engraftment and negligible retention in the recipient heart. PLoS One (2014) 9(5):e96725.10.1371/journal.pone.0096725
71. Kawaguchi N, Smith AJ, Waring CD, Hasan MK, Miyamoto S, Matsuoka R, et al. C-kit(pos) GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survivial through IGF-I paracrine signalling. PLoS One (2010) 5(12):e14297.10.1371/journal.pone.0014297
72. Ellison GM, Torella D, Dellegrottaglie S, Perez-Martinez C, de Prado AP, Vicinanza C, et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol (2011) 58(9):977–86.10.1016/j.jacc.2011.05.01321723061
73. Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet (2011) 378:1847–57.10.1016/S0140-6736(11)61590-022088800
74. 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) 126:54–64.10.1161/circulationaha.112.09262722965994
75. Keith MCL, Tang X-L, Tokita Y, Li Q-H, Ghafghazi S, Moore J, IV et al. Safety of intracoronary infusion of 20 million c-kit positive human cardiac stem cells in pigs. PLoS One (2015) 10(4):e0124227.10.1371/journal.pone.012422725905721
76. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LEJ, Berman D, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet (2012) 379:895–904.10.1016/S0140-6736(12)60195-022336189
77. Malliaras K, Makkar RR, Smith RR, Cheng K, Wu E, Bonow RO, et al. 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 (2014) 63(2):110–22.10.1016/j.jacc.2013.08.72424036024
78. Tan J-J, Carr CA, Stuckey DJ, Ellison GM, Messina E, Giacomello A, et al. Isolation and expansion of cardiosphere-derived stem cells. Curr Protoc Stem Cell Biol (2011) 16:2C.3.1–2C.3.12.10.1002/9780470151808.sc02c03s16
79. Wang B, Borazjani A, Tahai M, Curry AL, Simionescu DT, Guan J, et al. Fabrication of cardiac patch with decellularized porcine myocardial scaffold and bone marrow mononuclear cells. J Biomed Mater Res A (2010) 94(4):1100–10.10.1002/jbm.a.3278120694977
80. 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(9):e7195.10.1371/journal.pone.000719519779618
81. 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) 115:896–908.10.1161/CIRCULATIONAHA.106.65520917283259
82. Carr CA, Stuckey DJ, Tan JJ, Tan SC, Gomes RSM, Camelliti P, et al. Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks – an MRI study. PLoS One (2011) 6(10):e25669.10.1371/journal.pone.0025669
83. Johnston PV, Sasano T, Mills K, Evers R, Lee S-T, Smith RR, et al. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation (2009) 120:1075–83.10.1161/CIRCULATIONAHA.108.81605819738142
84. Chimenti I, Smith RR, Li T-S, 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) 106:971–80.10.1161/CIRCRESAHA.109.21068220110532
85. Makkar R, Schatz R, Traverse J, Hamer A, Beattie K, Smith RR, et al., editors. Allogeneic heart stem cells to achieve myocardial regeneration (ALLSTAR): the one year phase I results. AHA Scientific Conference. Chicago, IL: Circulation (2014).
86. Loffredo FS, Steinhauser ML, Gannon J, Lee RT. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell (2011) 8:389–98.10.1016/j.stem.2011.02.00221474103
87. Hatzistergos KE, Saur D, Seidler B, Balkan W, Breton M, Valasaki K, et al. Stimulatory effects of MSCs on cKit+ cardiac stem cells are mediated by SDF1/CXCR4 and SCF/cKit signaling pathways. Circ Res (2016) 119:921–30.10.1161/circresaha.116.309281
88. Suzuki G, Iyer V, Lee T-C, Canty JM, Jr. Autologous mesenchymal stem cells mobilize cKit+ and CD133- bone marrow progenitor cells and improve regional function in hibernating myocardium. Circ Res (2011) 109:1044–54.10.1161/CIRCRESAHA.111.245969
89. 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) 127:213–23.10.1161/circulationaha.112.13111023224061
90. Karantalis V, Suncion-Loescher VY, Bagno L, Golpanian S, Wolf A, Sanina C, et al. Synergistic effects of combined cell therapy for chronic ischemic cardiomyopathy. J Am Coll Cardiol (2015) 66(18):1990–9.10.1016/j.jacc.2015.08.87926516002
91. Kostin S, Popescu LM. A distinct type of cell in myocardium: interstitial Cajal-like cells (ICLCs). J Cell Mol Med (2009) 13(2):295–308.10.1111/j.1582-4934.2008.00668.x19183408
92. Popescu LM, Manole CG, Gherghiceanu M, Ardelean A, Nicolescu MI, Hinescu ME, et al. Telocytes in human epicardium. J Cell Mol Med (2010) 14(8):2085–93.10.1111/j.1582-4934.2010.01129.x20629996
93. Gherghiceanu M, Manole CG, Popescu LM. Telocytes in endocardium: electron microscope evidence. J Cell Mol Med (2010) 14(9):2330–4.10.1111/j.1582-4934.2010.01133.x20716125
94. Zhou Q, Wei L, Zhong C, Fu S, Bei Y, Huica RI, et al. Cardiac telocytes are double positive for CD34/PDGFR-alpha. J Cell Mol Med (2015) 19(8):2036–42.10.1111/jcmm.12615
95. Bani D, Formigli L, Gherghiceanu M, Faussone-Pellegrini MS. Telocytes as supporting cells for myocardial tissue organization in developing and adult heart. J Cell Mol Med (2010) 14(10):2531–8.10.1111/j.1582-4934.2010.01119.x20977627
96. Zhao B, Chen S, Liu J, Yuan Z, Qi X, Qin J, et al. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat. J Cell Mol Med (2013) 17(1):123–33.10.1111/j.1582-4934.2012.01655.x23205601
97. Zhao B, Liao Z, Chen S, Yuan Z, Yilin C, Lee KK, et al. Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post-infarcted cardiac function in rats. J Cell Mol Med (2014) 18(5):780–9.10.1111/jcmm.1225924655344
98. Gherghiceanu M, Popescu LM. Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images. J Cell Mol Med (2010) 14(4):871–7.10.1111/j.1582-4934.2010.01060.x20367663
99. Brade T, Kumar S, Cunningham TJ, Chatzi C, Zhao X, Cavallero S, et al. Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development (2011) 138(1):139–48.10.1242/dev.05423921138976
100. Wang J, Cao J, Dickson AL, Poss KD. Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling. Nature (2015) 522(7555):226–30.10.1038/nature1432525938716
101. Winter EM, van Oorschot AAM, Hogers B, van der Graaf LM, Doevendans PA, Poelmann RE, et al. A new direction for cardiac regeneration therapy: application of synergistically acting epicardium-derived cells and cardiomyocyte progenitor cells. Circulation (2009) 2(6):643–53.10.1161/circheartfailure.108.84372219919990
102. Winter EM, Grauss RW, Hogers B, van Tuyn J, van der Geest R, Lie-Venema H, et al. Preservation of left ventricular function and attenuation of remodeling after transplantation of human epicardium-derived cells into the infarcted mouse heart. Circulation (2007) 116:917–27.10.1161/CIRCULATIONAHA.106.66817817684151
103. Latham N, Ye B, Jackson R, Lam B-K, Kuraitis D, Ruel M, et al. Human blood and cardiac stem cells synergize to enhance cardiac repair when cotransplated into ischemic myocardium. Circulation (2013) 128:105–12.10.1161/circulationaha.112.000374
104. Campagnolo P, Cesselli D, Al Haj Zen A, Beltrami AP, Krankel N, Katare R, et al. Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential. Circulation (2010) 121(15):1735–45.10.1161/CIRCULATIONAHA.109.89925220368523
105. Katare R, Riu F, Mitchell K, Gubernator M, Campagnolo P, Cui Y, et al. Transplantation of human pericyte progenitor cells improves the repair of infarcted heart through activation of an angiogenic program involving micro-RNA-132. Circ Res (2011) 109(8):894–906.10.1161/CIRCRESAHA.111.25154621868695
106. Avolio E, Meloni M, Spencer HL, Riu F, Katare R, Mangialardi G, et al. Combined intramyocardial delivery of human pericytes and cardiac stem cells additively improves the healing of mouse infarcted hearts through stimulation of vascular and muscular repair. Circ Res (2015) 116:e81–94.10.1161/CIRCRESAHA.115.30614625801898
107. Nowbar AN, Mielewczik M, Karavassilis M, Dehbi HM, Shun-Shin MJ, Jones S, et al. Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis. BMJ (2014) 348:g2688.10.1136/bmj.g268824778175
108. Fisher SA, Doree C, Mathur A, Martin-Rendon E. Meta-analysis of cell therapy trials for patients with heart failure. Circ Res (2015) 116(8):1361–77.10.1161/CIRCRESAHA.116.30438625632038
109. Afzal MR, Samanta A, Shah ZI, Jeevanantham V, Abdel-Latif A, Zuba-Surma EK, et al. Adult bone marrow cell therapy for ischemic heart disease: evidence and insights from randomized controlled trials. Circ Res (2015) 117:558–75.10.1161/CIRCRESAHA.114.30479226160853
110. Menasché P, Vanneaux V, Hagège A, Bel A, Cholley B, Cacciapuoti I, et al. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J (2015) 36(30):2011–7.10.1093/eurheartj/ehv18925990469
111. Madonna R, Van Laake LW, Davidson SM, Engel FB, Hausenloy DJ, Lecour S, et al. Position paper of the European Society of Cardiology Working Group cellular biology of the heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure. Eur Heart J (2016) 37(23):1789–98.10.1093/eurheartj/ehw11327055812
112. Ott HC, Matthiesen TS, Goh S-K, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med (2008) 14(2):213–21.10.1038/nm1684
113. Lu TY, Lin B, Kim J, Sullivan M, Tobita K, Salama G, et al. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun (2013) 4:2307.10.1038/ncomms330723942048
114. Guyette JP, Charest JM, Mills RW, Jank BJ, Moser PT, Gilpin SE, et al. Bioengineering human myocardium on native extracellular matrix. Circ Res (2016) 118:56–72.10.1161/CIRCRESAHA.115.30687426503464