Stimulation of the epicardium as a source of myocardial repair: from experiment to clinical practice

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Abstract

Mortality from myocardial infarction and its complications — heart rhythm disturbances, myocardial remodeling with subsequent development of congestive heart failure — occupies a leading place in the world. Activation of the epicardium is being actively studied as one of the ways to prevent cardiac remodeling. The method is based on the ability of embryonic epicardial cells to undergo epithelial-mesenchymal transformation, as a result of which the resulting epicardial-derived cells give rise to various cytological lines — cardiac fibroblasts, smooth muscle cells of the vascular wall, adipocytes and cardiomyocytes. In the postnatal period, this regenerative potential is absent. Currently, various methods have been developed to activate the reparative potential of the epicardium using options for genetic reprogramming of epicardial cells using viral vectors, exposure to paracrine factors involved in the formation of the heart and its structures — transcription factors GATA4, GATA6, thymosin-β4, introduction of embryonic stem cells or induced pluripotent stem cells in tissue-engineered constructs, activation of fibroblast growth factors ( FGF ), and platelet-derived growth factor ( PDGF ). These methods are being actively studied in experimental models of myocardial infarction and have shown their high efficiency in vitro. The results of transplantation of tissue-engineered structures during coronary artery bypass surgery in patients with severe post-infarction heart failure show promise in terms of slowing down myocardial remodeling.

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About the authors

Eugene V. Timofeev

Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: darrieux@mail.ru
ORCID iD: 0000-0001-9607-4028
SPIN-code: 1979-7713

MD, PhD, Dr. Sci. (Medicine), Professor, Department of Propaedeutics Internal Medicine

Russian Federation, 2 Litovskaya st., Saint Petersburg, 194100

Yana E. Bulavko

Saint Petersburg State Pediatric Medical University

Email: yana.bulavko@mail.ru
ORCID iD: 0000-0003-0879-846X
SPIN-code: 8159-2273

Assistant Professor, Department of Propaedeutics Internal Medicine

Russian Federation, 2 Litovskaya st., Saint Petersburg, 194100

References

  1. Dergilev K V, Komova AV, Tsokolaeva ZI, et al. Epicardium as a new target for regenerative technologies in cardiology. Genes and Cells. 2020;15(2):33–40. EDN: ZWNMPT doi: 10.23868/202004016
  2. Dergilev KV, Tsokolaeva ZI, Beloglazova IB, et al. Intramiocardial administration of resident c-kit + cardiac progenital cells activates epicardial progenitor cells and promotes myocardial vascularation after the infarction. Genes and Cells. 2018;13(1):75–81. EDN: YNQDYD doi: 10.23868/201805009
  3. Dergilev K V, Tsokolaeva ZI, Beloglazova IB, et al. Epicardial transplantation of adipose mesenchymal stromal cell sheets promotes epicardial activation and stimulates angiogenesis in myocardial infarction (experimental study). General Reanimatology. 2019;15(6): 38–49. EDN: YLCBGN doi: 10.15360/1813-9779-2019-6-38-49
  4. Sizov AV, Zotov DD. Myocardial infarction of the second type with severe aortic stenosis. University Therapeutic Journal. 2022;4(1): 32–36. doi : 10.56871/5991.2022.32.45.004
  5. Shloydo EA, Pyaterichenko IA, Zvereva VV, et al. Endovascular treatment in patients with combined pathology. Pediatrician (St. Petersburg). 2015;6( 3):123–128. EDN: VBUCZP doi: 10.17816/PED63123-128
  6. Bao X, Lian X, Hacker TA, et al. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat Biomed Eng. 2016;1:0003. doi: 10.1038/s41551-016-0003
  7. Cai C-L, Martin JC, Sun Y, et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454:104–108. doi: 10.1038/nature06969
  8. Cai W, Tan J, Yan J, et al. Limited regeneration potential with minimal epicardial progenitor conversions in the neonatal mouse heart after injury. Cell Rep. 2019;28(1):190–201.e3. doi: 10.1016/j.celrep.2019.06.003
  9. Cao J, Poss KD. The epicardium as a hub for heart regeneration. Nat Rev Cardiol. 2018;15:631–647. doi: 10.1038/s41569-018-0046-4
  10. Chiu LLY, Reis LA, Momen A, Radisic M. Controlled release of thymosin-β4 from injected collagen-chitosan hydrogels promotes angiogenesis and prevents tissue loss after myocardial infarction. Regen Med. 2012;7(4):523–533. doi: 10.2217/rme.12.35
  11. Christoffels VM, Grieskamp T, Norden J, et al. Tbx18 and the fate of epicardial progenitors. Nature. 2009;458(7240):E8–E9. doi: 10.1038/nature07916
  12. Davis ME, Motion JP, Narmoneva DA, et al. Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation. 2005;111(4):442–450. doi: 10.1161/01.CIR.0000153847.47301.80
  13. Gaetani R, Feyen DAM, Verhage V, et al. Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials. 2015;61:339–348. doi: 10.1016/j.biomaterials.2015.05.005
  14. Guadix JA, Orlova VV, Giacomelli E, et al. Human pluripotent stem cell differentiation into functional epicardial progenitor cells. Stem Cell Rep. 2017;9(6):1754–1764. doi: 10.1016/j.stemcr.2017.10.023
  15. Iyer D, Gambardella L, Bernard WG, et al. Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Development. 2015;142(8):1528–1541. doi: 10.1242/dev.119271
  16. Kobayashi H, Yu Y, Volk DE. Chapter 13 — Thymosins. In: Litwack G, editor. Hormonal signaling in biology and medicine. Academic Press; 2020. P. 311–326. doi: 10.1016/B978-0-12-8 13814-4.00013-4
  17. Mewhort HE, Turnbull JD, Meijndert HC, et al. Epicardial infarct repair with basic fibroblast growth factor-enhanced CorMatrix-ECM biomaterial attenuates postischemic cardiac remodeling. J Thorac Cardiovasc Surg. 2014;147(5):1650–1659. doi: 10.1016/j.jtcvs.2013.08.005
  18. Miyagawa S, Domae K, Yoshikawa Y, et al. Phase I clinical trial of autologous stem cell-sheet transplantation therapy for treating cardiomyopathy. J Am Heart Assoc. 2017;6(4):e003918. doi: 10.1161/JAHA.116.003918
  19. Moerkamp AT, Lodder K, van Herwaarden T, et al. Human fetal and adult epicardial-derived cells: A novel model to study their activation. Stem Cell Res Ther. 2016;7:174. doi: 10.1186/s13287-016-0434-9
  20. Olivey HE, Svensson EC. Epicardial-myocardial signaling directing coronary vasculogenesis. Circ Res. 2010;106(5):818–832. doi: 10.1161/CIRCRESAHA.109.209197
  21. Pascual-Gil S, Garbayo E, Díaz-Herráez P, et al. Heart regeneration after myocardial infarction using synthetic biomaterials. J Control Release. 2015;203:23–38. doi: 10.1016/j.jconrel.2015.02.009
  22. Paunovic AI, Drowley L, Nordqvist A, et al. Phenotypic screen for cardiac regeneration identifies molecules with differential activity in human epicardium-derived cells versus cardiac fibroblasts. ACS Chem Biol. 2017;12(1):132–141. doi: 10.1021/acschembio.6b00683
  23. Porrello ER, Mahmoud AI, Simpson E, et al. Transient regenerative potential of the neonatal mouse heart. Science. 2011;331(6020):1078–1080. doi: 10.1126/science.1200708
  24. Rane AA, Chuang JS, Shah A, et al. Increased infarct wall thickness by a bio-inert material is insufficient to prevent negative left ventricular remodeling after myocardial infarction. PLoS One. 2011;6: e21571. doi: 10.1371/journal.pone.0021571
  25. Sanchez-Fernandez C, Rodriguez-Outeiriño L, Matias-Valiente L, et al. Regulation of epicardial cell fate during cardiac development and disease: An overview. Int J Mol Sci. 2022;23(6):3220. doi: 10.3390/ijms23063220
  26. Sasaki T, Hwang H, Nguyen C, et al. The small molecule Wnt signaling modulator ICG-001 improves contractile function in chronically infarcted rat myocardium. PLoS One. 2013;8:e75010. doi: 10.1371/journal.pone.0075010
  27. Serpooshan V, Zhao M, Metzler SA, et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials. 2013;34(36): 9048–9055. doi: 10.1016/j.biomaterials.2013.08.017
  28. Shrivastava S, Srivastava D, Olson EN, et al. Thymosin β4 and cardiac repair. Ann NY Acad Sci. 2010;1194(1):87–96. doi: 10.1111/j.1749-6632.2010.05468.x
  29. Smart N, Risebro CA, Melville AAD, et al. Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445:177–182. doi: 10.1038/nature05383
  30. Smits A, Riley P. Epicardium-derived heart repair. J Dev Biol. 2014;2(2):84–100. doi: 10.3390/jdb2020084
  31. Smits AM, Dronkers E, Goumans M-J. The epicardium as a source of multipotent adult cardiac progenitor cells: Their origin, role and fate. Pharmacol Res. 2018;127:129–140. doi: 10.1016/j.phrs.2017.07.020
  32. Tan SH, Loo SJ, Gao Y, et al. Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction. Theranostics. 2021;11(16):7879–7895. doi: 10.7150/thno.56757
  33. Tano N, Narita T, Kaneko M, et al. Epicardial placement of mesenchymal stromal cell-sheets for the treatment of ischemic cardiomyopathy; in vivo proof-of-concept study. Mol Ther. 2014;22(10): 1864–1871. doi: 10.1038/mt.2014.110
  34. Trembley MA, Velasquez LS, Bentley KLDM, Small EM. Myocardin-related transcription factors control the motility of epicardium-derived cells and the maturation of coronary vessels. Development. 2015;142(1):21–30. doi: 10.1242/dev.116418
  35. Van Tuyn J, Atsma DE, Winter EM, et al. Epicardial cells of human adults can undergo an epithelial-to-mesenchymal transition and obtain characteristics of smooth muscle cells in vitro. Stem Cells. 2007;25(2):271–278. doi: 10.1634/stemcells.2006-0366
  36. Van Wijk B, Gunst QD, Moorman AFM, Van Den Hoff MJB. Cardiac regeneration from activated epicardium. PLoS One. 2012;7:e44692. doi: 10.1371/journal.pone.0044692
  37. Vieira JM, Howard S, Villa Del Campo C, et al. BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease. Nat Commun. 2017;8:16034. doi: 10.1038/ncomms16034
  38. Von Gise A, Pu WT. Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease. Circ Res. 2012;110(12):1628–1645. doi: 10.1161/CIRCRESAHA.111.259960
  39. Wang QL, Wang H-J, Li Z-H, et al. Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium. J Cell Mol Med. 2017;21(9):1751–1766. doi: 10.1111/jcmm.13097
  40. Wang Y-L, Yu S-N, Shen H-R, et al. Thymosin β4 released from functionalized self-assembling peptide activates epicardium and enhances repair of infarcted myocardium. Theranostics. 2021;11(9):4262–4280. doi: 10.7150/thno.52309
  41. Wei K, Serpooshan V, Hurtado C, et al. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature. 2015;525:479–485. doi: 10.1038/nature15372
  42. Wessels A, Pérez-Pomares JM. The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec Part A Discov Mol Cell Evol Biol. 2004;276A(1):43–57. doi: 10.1002/ar.a.10129
  43. Winter EM, Grauss RW, Hogers B, 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(8):917–927. doi: 10.1161/CIRCULATIONAHA.106.668178
  44. Witty AD, Mihic A, Tam RY, et al. Generation of the epicardial lineage from human pluripotent stem cells. Nat Biotechnol. 2014;32:1026–1035. doi: 10.1038/nbt.3002
  45. Yamaguchi Y, Cavallero S, Patterson M, et al. Adipogenesis and epicardial adipose tissue: a novel fate of the epicardium induced by mesenchymal transformation and PPARgamma activation. PNAS USA. 2015;112(7):2070–2075. doi: 10.1073/pnas.1417232112
  46. Zhao J, Cao H, Tian L, et al. Efficient differentiation of TBX18 + /WT1 + epicardial-like cells from human pluripotent stem cells using small molecular compounds. Stem Cells Dev. 2017;26(7):528–540. doi: 10.1089/scd.2016.0208
  47. Zhou B, Ma Q, Rajagopal S, et al. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008;454(7200):109–913. doi: 10.1038/nature07060
  48. Zhou B, Mcgowan FX, Pu WT, et al. Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J Clin Investig. 2011;121(5):1894–1904. doi: 10.1172/JCI45529

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