Morphological changes in fibrous tissue of rat myocardium after administration of dispersed allogeneic biomaterial

Document Type : Original Article

Authors

1 Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation, Ufa, Russia

2 Federal State Budgetary Educational Institution of Higher Education, Saint Petersburg State University of Veterinary Medicine, Saint Petersburg, Russia

Abstract
To improve the structure of the heart muscle after myocardial infarction, methods of regenerative medicine are used. One of the promising areas is the intra-myocardial administration of acellular allogeneic biomaterial (AB). The AB stimulates the regeneration of organs and tissues. But, the effect of AB on the myocardium after its fibrous ischemic degeneration has not been assessed. The aim of the study was to assess the morphological structure of the heart after cryodestruction in the late period and the use of AB. Chronic myocardial infarction was modeled in 80 male rats. To simulate chronic myocardial infarction and fibrosis formation, contact cryodestruction was performed. After 45 days, during repeated thoracotomy in the main group, AB suspension was injected into the area of the cryogenic myocardial scar. Six injections of 0.50 mg of dry substance were administered. In the control group, physiological solution was injected. After AB administration, following 7, 14, 30, and 45 days, the animals were withdrawn from the experiment, and the hearts were excised for histological and immunohistochemical studies. The AB underwent gradual phagocytosis by macrophages and gradually replaced by loose fibrous connective tissue with the presence of cardiac troponin I+ labeled muscle cells, which over time underwent hypertrophy. Cardiomyocytes were grouped in the AB implantation zone as separate clusters. The heart mass did not change in both experimental groups. The use of AB in the area of the formed cryogenic myocardial scar promoted the transformation of dense fibrous connective tissue into loose tissue and its replacement with cardiac muscle tissue.

Keywords

Subjects


  1. Baryshev VA, Popova OS, Ponamarev VS. New methods for detoxification of heavy metals and mycotoxins in dairy cows. OJAFR 2022; 12(2): 81-88.
  2. Kuznetsov YE, Lunegov AM, Ponomarev VS, et al. Correlation interaction of total bile acids with basic blood biochemical indicators in minks (Mustela vison Schreber, 1777). Agric Biol 2022; 57(6): 1217-1224.
  3. Alekhin YN, Popova OS, Ponomarev VS, et al. The effect of farnesoid X receptor agonist on postprandial lipemia in rats fed a supraphysiological fat dozes [Russian]. Drug Dev Regist 2023; 12(2): 174-184.
  4. Ponamarev V, Popova O, Kostrova A, et al. The concept of development of new ecologically based methods of diagnostics and pharmacocorrection in veterinary medicine (on the example of pathologies of the hepatobiliary system). AIP Conf Proc 2023; 3011: 020028. doi: 10.1063/5.0161092.
  5. Ponamarev V, Popova O, Kostrova A, et al. A new method for assessing the toxic properties of various medicinal substances on the hepatobiliary system functionality in the context of the ecopharmacology development. AIP Conf Proc 2023; 3011: 20027. doi: 10.1063/5.0161091.
  6. Prusakova AV, Zelenevskiy NV, Prusakov AV, et al. Ultrastructural organization of liver hepatocytes of the Anglo-Nubian goat. Veterinarski Glasnik 2023; 77(2): 176-187.
  7. Prusakova A, Zelenevskiy N, Prusakov A, et al. Organization of histo-hematic barriers of the liver in Anglo-Nubian goat. OJAFR 2023; 13(4): 242-245.
  8. Hare JM, Fishman JE, Gerstenblith G, et al. 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 2012; 308(22): 2369-2379.
  9. Parfenova EV. Heart stem cells: fact or fantasy [Russian]? Russ J Cardiol 2019; 11: 84-90.
  10. Borzenok SA, Gushchina MB, Afanasieva DS, et al. Orbital adipose tissue - a new resource for transplantation [Russian]. Bull Transplant Artif Organs. 2015; 17(4): 118-123.
  11. Bolli R, Mitrani RD, Hare JM, et al. A Phase II study of autologous mesenchymal stromal cells and c‐kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT‐HF trial. Eur J Heart Fail 2021; 23(4): 661-674.
  12. Nakamura K, Murry CE. Function follows form -a review of cardiac cell therapy. Circulation 2019; 83(12): 2399-2412.
  13. Grover GN, Rao N, Christman KL. Myocardial matrix-polyethylene glycol hybrid hydrogels for tissue Nanotechnol 2014; 25(1): 014011. doi: 10.1088/0957-4484/25/1/014011.
  14. Ghosh M, Halperin-Sternfeld M, Adler-Abramovich L. Bio mimicking of extracellular matrix. In: Perrett S, Buell A, Knowles T. (eds) Biological and bio-inspired nanomaterials. Advances in experimental medicine and biology, vol 1174. Singapore, Singapore: Springer 2019; 371-399.
  15. Di Franco S, Amarelli C, Montalto A, et al. Biomaterials and heart recovery: cardiac repair, regeneration and healing in the MCS era: a state of the "heart". J Thorac Dis 2018; 10(Suppl 20): S2346-S2362.
  16. Muldashev ER. Alloplant technologies as an innovative model of regenerative surgery [Russian]. Prac Med 2019; 17(1): 12-16.
  17. Lebedeva AI, Muslimov SA, Musina LA, et al. Effect of intramyocardial allogenic biomaterial injection on angiogenesis and postischemic scar remodeling in rats [Russian]. Russ J Transplantol Artif Organs 2020; 22(3): 156-166.
  18. Lebedeva AI, Muslimov SA, Gareev EM, et al. Allogeneic biomaterial as an inductor of regeneration in the myocardium injured by experimental ischemia [Russian]. Pathol Physiol Exp Ther 2021; 65(1): 60-69.
  19. Lebedeva AI, Muslimov SA, Gareev EM, et al. Stimulation of autologous progenitorial and committed cells in ischemically damaged myocardium [Russian]. Russ J Cardiol 2018; 23(11): 123-129.
  20. Bayat A, McGrouther DA, Ferguson MWJ. Skin scarring. BMJ 2003; 326: 88. doi: 10.1136/bmj.326.7380.88.
  21. Yao Q, Zheng YW, Lan QH, et al. Recent development and biomedical applications of decellularized extracellular matrix biomaterials. Mater Sci Eng C Mater Biol Appl 2019; 104: 109942. doi: 10.1016/j.msec.2019.109942.
  22. Bejleri D, Davis ME. Decellularized extracellular matrix materials for cardiac repair and regeneration. Adv Healthc Mater 2019; 8(5): e1801217. doi: 10.1002/adhm.201801217.
  23. Wang CC, Chen CH, Hwang SM, et al. Spherically symmetric mesenchymal stromal cell bodies inherent with endogenous extracellular matrices for cellular cardiomyoplasty. Stem Cells 2009; 27(3): 724-732
  24. Afanasiev SA, Rogovskaya YV, Falaleeva LP, et al. Comparative assessment of heart remodeling in rats after experimental coronary stenosis and cryodestruction [Russian]. Bull Exp Biol Med 2009; 147: 695-697.
  25. Karkishchenko VN, Pomytkin IA, Petrova NV, et al. Exhaustive physical exercise causes a multiple increase in the transcription of HMGB1 gene in mini pigs’ lymphocytes [Russian]. J Biomed 2022; 18(1): 22-31.
  26. Rebrova OY. Statistical analysis of medical data. Application software package STATISTICA [Russian]. Moscow, Russia: MediaSphere 2002: 21-312.
  27. Nepomnyashchikh LM, Lushnikova EL, Bakarev MA, et al. Immunohistochemical analysis of MMP-2 expression in the myocardium during the postinfarction period. Bull Exp Biol Med 2015; 159(4): 505-510.
  28. Lebedeva AI, Afanasiev SA, Kondratyeva DS, et al. Correction of cicatricial changes in subacute stage of myocardial infarction with using of dispersed allogenic biomaterial [Russian]. Russ J Cardiol 2019; 24(7): 68-74.
  29. Musina LA, Lebedeva AI, Shangina OR. Application of alloplant biomaterials for peripheral nerve regeneration (experimental morphological study) [Russian]. Bull Transplantol Artif Organs 2024; 26(S): 196. doi: 15825/1995-1191-2024-S-196.
  30. Bulysheva AA, Burcus N, Lundberg CG, et al. VEGF-B electrotransfer mediated gene therapy induces cardiomyogenesis in a rat model of cardiac ischemia. Bioelectrochemistry 2018; 124: 105-111.
Volume 16, Issue 7
July 2025
Pages 381-386

  • Receive Date 16 July 2024
  • Revise Date 12 September 2024
  • Accept Date 15 September 2024