Clinical Physiology of Circulation

ISSN 1814-6910 (Print)
ISSN 2410-9134 (Online)

 

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Issue's catalogue ➤ КФК. 2021; 18 (2): 93-180 ➤ Эволюция подходов к жизнеспособности и девитализации аллографтов и разработка нового метода децеллюляризации. Клеточная модификация аллографтов

Evolution of approaches to the viability and devitalization of allografts and development of a new method of decellularization. Cellular modification of allografts

Authors: Britikov D.V., Akatov V.S., Chashchin I.S., Zubko A.V., Muratov R.M.

Company:
1 Bakoulev National Medical Research Center for Cardiovascular Surgery, Moscow, 121552, Russian Federation
2 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2021-18-2-128-138

UDC: 577.1:616.126.3-089.28/29

Link: Clinical Physiology of Blood Circulaiton. 2021; 2 (18): 118-127

Quote as: Britikov D.V., Akatov V.S., Chashchin I.S., Zubko A.V., Muratov R.M. Evolution of approaches to the viability and devitalization of allografts and development of a new method of decellularization. Cellular modification of allografts. Clinical Physiology of Circulation. 2021; 18 (2): 128–38 (in Russ.). DOI: 10.24022/1814-6910-2021-18-2-128-138

Keywords:  allograft devitalization decellularization cryopreservation recellularization cardiovascular surgery bioprosthetics

Received / Accepted:  26.02.2021 / 01.03.2021

Full text:  

Abstract

The idea of using homologous heart valves and large vessels appeared about 70 years ago. Experimental studies of C.R. Lam were the basis for further research. To date, the interest of cardiac surgeons in the use of "substitutes" for damaged heart valves made of allogeneic tissue, created by nature and perfectly corresponding to anatomical and physiological parameters, has not faded, despite the abundance of various mechanical and biological structures. In the history of the development of allogeneic bioprosthetics in Bakoulev Center, there are 3 stages. The first stage is the reproduction of the technique of sampling, sterilization and cryopreservation of tissue valves, taking into account the available information from the Virginia Tissue Bank, the London Heart and Lung Institute and the European Tissue Bank. The second stage is associated with the maximum preservation of the donor's own cells in the tissue of the transplanted valve. For a long time, it was believed that the presence of living donor fibroblasts in the graft contributes to their dispersal and replacement of the tissue matrix damaged during wear. If more than 80% of the donor's viable cells are preserved in the graft, it can be argued that the tissue has virtually no damage significant for normal functioning. The third stage is associated with the devitalization of allografts. The process of death of donor fibroblasts and colonization of the valve with recipient fibroblasts is ongoing. Its rate is influenced by the immunological characteristics of the recipient, the hemodynamics of the allograft, and many other factors. Probably more important is the preservation of the cell-free structure of the allograft, the matrix that is then populated by the recipient's fibroblasts. Viable cells may be only an indirect indicator of the quality of the tissue condition. The aortic wall secretes the antigens of the main histocompatibility complex and stimulates the immune response, but it is much less pronounced than the response caused by the endothelium. Further efforts of the researchers were aimed at sparing the elimination of donor cells from the matrix. The third stage, which continues to the present time, is devoted not only to the elimination of donor cells, but also to the removal of their remnants from the implanted tissues. At the same time, the main attention is paid to the creation of "comfortable" conditions for the population of recipient cells in the allograft tissue, primarily – tissue-forming connective tissue cells capable of further self-renewal. As shown by the second stage studies, chemical devitalization leads to cell death, but their fragments remain in the interstitial matrix, causing calcification and preventing revitalization. The third stage of the study involves the development of a combined technique of physical and chemical devitalization, or rather, complete decellularization of the graft tissues and its colonization with the recipient's tissue-forming cells.

References

  1. Lam C.R., Aram H.H., Mennell E.R. An experimentel study of aortic valve homografts. Surg. Gynecol. Obstetr. 1952; 94: 129–35.
  2. Ross D. Technique of aortic valve replacement with a homograft: orthotopic replacement. Ann. Thorac. Surg. 1991; 52: 154–6. DOI: 10.1016/0003-4975(91)91449-6
  3. Акатов B.C., Фесенко Н.И., Соловьев В.В., Фадеева И.Е., Чеканов А.В., Муратов Р.М. и др. Подавление кальцификации трансплантатов клапанов сердца путем их девитализации. Клеточная трансплантология и тканевая инженерия. 2010; 5 (1): 41–6.
  4. Armiger L.C. Post-implantation patterns of leaflet cellularity in heart valve allografts: are persisting donor cells beneficial or detrimental? VII International Symposium "Cardiac Bioprostheses", Barcelona, Spain; 1997: 114.
  5. Armiger L.C. Postimplantation leaflet cellularity of valve allografts: are donor cells beneficial or detrimental? Ann. Thorac. Surg. (United States). 1998; 66 (Suppl. 6): pS233–5. DOI: 10.1016/s0003- 4975(98)00984-9
  6. Hazekamp M.G., Koolbergen D.R., Braun J., Sugihara H., Cornelisse C.J., Goffin Y.A. et al. In situ hybridisation: a new technique determine fibroblast origin in cryopre-served aortic homograft valve explants. J. Thorac. Cardiovasc. Surg. 1995; 110: 248–57. DOI: 10.1016/S0022-5223(05)80031-5
  7. Koolbergen P.R., Hazekamp M.G., Kurvers M., de Heer E., Comelisse C.J., Huysmans H.A. et al. Tissue chimerism in human cryopreserved homograft valve explants demonstrated by in situ hybridization. Ann. Thorac. Surg. (United States). 1998; 66 (Suppl. 6): S225–32.
  8. Yankah A.C., Wottge H.U. Allograft conduit wall calcification in a model of chronic arterial graft rejection. J. Card. Surg. (United States). 1997; 12 (2): 86–92. DOI: 10.1111/j.1540-8191.1997.tb00100.x
  9. Khatib H.E., Lupinetti F.M. Antigenicity of fresh and cryopreserved rat valve allografts. Transplantation. 1990; 49: 765–7. DOI: 10.1097/00007890-199004000-00022
  10. Moustapha A., Ross D.B., Bittira B., Van-Velzen D., McAlister V.C., Lannon C.L. et al. Aortic valve grafts in the rat: evidence for rejection. J. Thorac. Cardiovasc. Surg. 1997; 114 (6): 891–902. DOI: 10.1016/S0022- 5223(97)70002-3
  11. Hogan P., Duplock L., Green M., Smith S., Gall K.L., Frazer I.H. et al. Human aortic valve allografts elicit a donor-specific immune response. J. Thorac. Cardiovasc. Surg. 1996; 112 (5): 1260–7. DOI: 10.1016/S0022-5223(96)70139-3
  12. Barratt-Boyes B.G., Roche A.H., Subramanyan R., Pemberton J.R., Whitlock R.M. Long-term follow-up on patients with the antibiotic-sterilised aortic homograft valve inserted freehand in the aortic position. Circulation. 1987; 75: 768–77. DOI: 10.1161/01.cir.75.4.768
  13. Акатов В.С., Рындина Н.И., Муратов Р.М., Санталова И.М., Соловьев В.В., Бритиков Д.В. и др. Участие митохондрий в инициации кальциноза в трансплантатах клапанов сердца и сосудов. Доклады Академии наук. 2006; 406 (6): 832–4.
  14. Бритиков Д.В., Чащин И.С., Хугаев Г.А., Бакулева Н.П. Девитализация аллографтов сверхкритическим диоксидом углерода и детергентами. Экспериментальная оценка. Сердечно-сосудистые заболевания. Бюллетень НЦССХ им. А.Н. Бакулева РАМН. 2019; 20 (5): 402–9. DOI: 10.24022/1810-0694-2019-20-5-402-409
****
  1. Lam C.R., Aram H.H., Mennell E.R. An experimentel study of aortic valve homografts. Surg. Gynecol. Obstetr. 1952; 94: 129–35.
  2. Ross D. Technique of aortic valve replacement with a homograft: orthotopic replacement. Ann. Thorac. Surg. 1991; 52: 154–6. DOI: 10.1016/0003-4975(91)91449-6
  3. Akatov V.S., Fesenko N.I., Solov’ev V.V., Fadeeva I.E., Chekanov A.V., Muratov R.M. et al. Suppression of calcification of heart valve grafts by devitalizing them. Cell Transplantation and Tissue Engineering. 2010; 5 (1): 41–6 (in Russ.).
  4. Armiger L.C. Post-implantation patterns of leaflet cellularity in heart valve allografts: are persisting donor cells beneficial or detrimental? VII International Symposium "Cardiac Bioprostheses", Barcelona, Spain; 1997: 114.
  5. Armiger L.C. Postimplantation leaflet cellularity of valve allografts: are donor cells beneficial or detrimental? Ann. Thorac. Surg. (United States). 1998; 66 (Suppl. 6): pS233–5. DOI: 10.1016/s0003- 4975(98)00984-9
  6. Hazekamp M.G., Koolbergen D.R., Braun J., Sugihara H., Cornelisse C.J., Goffin Y.A. et al. In situ hybridisation: a new technique determine fibroblast origin in cryopre-served aortic homograft valve explants. J. Thorac. Cardiovasc. Surg. 1995; 110: 248–57. DOI: 10.1016/S0022-5223(05)80031-5
  7. Koolbergen P.R., Hazekamp M.G., Kurvers M., de Heer E., Comelisse C.J., Huysmans H.A. et al. Tissue chimerism in human cryopreserved homograft valve explants demonstrated by in situ hybridization. Ann. Thorac. Surg. (United States). 1998; 66 (Suppl. 6): S225–32.
  8. Yankah A.C., Wottge H.U. Allograft conduit wall calcification in a model of chronic arterial graft rejection. J. Card. Surg. (United States). 1997; 12 (2): 86–92. DOI: 10.1111/j.1540-8191.1997.tb00100.x
  9. Khatib H.E., Lupinetti F.M. Antigenicity of fresh and cryopreserved rat valve allografts. Transplantation. 1990; 49: 765–7. DOI: 10.1097/00007890-199004000-00022
  10. Moustapha A., Ross D.B., Bittira B., Van-Velzen D., McAlister V.C., Lannon C.L. et al. Aortic valve grafts in the rat: evidence for rejection. J. Thorac. Cardiovasc. Surg. 1997; 114 (6): 891–902. DOI: 10.1016/S0022- 5223(97)70002-3
  11. Hogan P., Duplock L., Green M., Smith S., Gall K.L., Frazer I.H. et al. Human aortic valve allografts elicit a donor-specific immune response. J. Thorac. Cardiovasc. Surg. 1996; 112 (5): 1260–7. DOI: 10.1016/S0022-5223(96)70139-3
  12. Barratt-Boyes B.G., Roche A.H., Subramanyan R., Pemberton J.R., Whitlock R.M. Long-term follow-up on patients with the antibiotic-sterilised aortic homograft valve inserted freehand in the aortic position. Circulation. 1987; 75: 768–77. DOI: 10.1161/01.cir.75.4.768
  13. Akatov V.S., Ryndina N.I., Muratov R.M., Santalova I.M., Soloviev V.V., Britikov D.V. et al. Participation of mitochondria in the initiation of calcification in heart valve grafts and vessels. Reports of the Academy of Sciences. 2006; 406 (6): 832–4 (in Russ.).
  14. Britikov D.V., Chashchin I.S., Khugaev G.A., Bakuleva N.P. The decellularization of allografts with supercritical carbon dioxide and detergents. Experimental data. The Bulletin of Bakoulev Center. Cardiovascular Diseases. 2019; 20 (5): 402–9 (in Russ.). DOI: 10.24022/1810-0694-2019-20-5-402- 409

About Authors

  • Dmitriy V. Britikov, Dr. Med. Sc., Head of Group of Experimental Development of Biological Materials for Cardiovascular Surgery; ORCID
  • Vladimir S. Akatov, Dr. Phys.-Math. Sc., Professor, Deputy Director for Research; ORCID
  • Ivan S. Chashchin, Cand. Phys.-Math. Sc., Lead Technologist; ORCID
  • Aleksandr V. Zubko, Cand. Med. Sc., Head of Cell Technologies and Molecular-Genetic Research Group; ORCID
  • Ravil’ M. Muratov, Dr. Med. Sc., Professor, Head of Department of Urgent Surgery for Acquired Heart Diseases; ORCID

 If you found mistakes, select text and press Alt+A