FOR A RENAL DECELLULARIZATION PROTOCOL WITH SUBSEQUENT COMPREHENSIVE ASSESSMENT OF THE BIOLOGICAL SCAFFOLD


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Chronic renal failure (CRF) is one of the most challenging problems of contemporary medicine. Patients with chronic renal failure usually need renal replacement therapy as either hemodialysis, peritoneal dialysis or a kidney transplant. The latter is the most promising option for end-stage kidney disease. However, the shortage of donor organs, the complexity of their delivery, the difficulty in finding an immunologically compatible donor and the need for lifelong immunosuppression triggered advances in modern tissue engineering. In this field, the primary priority is focused on developing bioengineered scaffolds with subsequent recellularization with autologous cells. Using such constructs would allow for solving both ethical and immunological problems of transplantation. The aim of this pilot study was to develop a new method of renal decellularization using small laboratory animals. Materials and Methods. The study investigated the morphological structure of the obtained decellularized matrix and quantitatively tested DNA residues in the resulting scaffold. We proposed a new biophysical method for assessing the matrix quality using the EPR spectroscopy and conducted experiments on the matrix recellularization with mesenchymal multipotent stem cells to estimate cytotoxicity, cell viability and metabolic activity. Results. The obtained decellularized renal matrix retained the native tissue architecture after a complete removal of the cell material, had no cytotoxic properties and supported cell adhesion and proliferation. Conclusion. All the above suggests that the proposed decellularization protocol is a promising method to produce tissue-engineered kidney constructs with possible clinical application in the foreseeable future.

Full Text

Restricted Access

About the authors

P. V Glybochko

I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation

Email: rektorat@mma.ru
Academician of the RAS, Dr.Med.Sci., Prof., Rector Moscow, Russia

S. N Alekseenko

Kuban State Medical University of Minzdrav of Russia

Email: corpus@ksma.ru
Dr.Med.Sci., Prof., Rector Krasnodar, Russia

E. A Gubareva

Kuban State Medical University of Minzdrav of Russia

Email: g_lena82@list.ru
PhD, Head of the Laboratory of Basic Research in the Field of Regenerative Medicine Krasnodar, Russia

E. V Kuevda

Kuban State Medical University of Minzdrav of Russia

Email: elenakuevda@yandex.ru
PhD, Research Fellow at the Faboratory of Basic Research in the Field of Regenerative Medicine Krasnodar, Russia

A. A Basov

Kuban State Medical University of Minzdrav of Russia

Email: son_sunytch79@mail.ru
Dr.Med.Sci., Professor at the Department of Fundamental and CUnical Biochemistry Krasnodar, Russia

A. S Sotnichenko

Kuban State Medical University of Minzdrav of Russia

Email: alex24.88@mail.ru
PhD, Research Fellow at the Laboratory of Basic Research in the Field of Regenerative Medicine Krasnodar, Russia

S. S Dzhimak

Kuban State University

Email: jimack@mail.ru
PhD, Associate Professor at the Department of Radiophysics and Nanotechnology Krasnodar, Russia

I. S Gumenyuk

Kuban State Medical University of Minzdrav of Russia

Email: meklon@gmail.com
PhD, Research Fellow at the Faboratory of Basic Research in the Field of Regenerative Medicine Krasnodar, Russia

I. Kh Egiev

Kuban State Medical University of Minzdrav of Russia

Email: ivan.egiev@mail.ru
Fifth Year Student, Faculty of Pediatrics Krasnodar, Russia

V. N Chechelyan

Kuban State Medical University of Minzdrav of Russia

Email: valera.chechelian2013@yandex.ru
Fifth Year Student, Medical Faculty Krasnodar, Russia

R. Z Nakokhov

Kuban State Medical University of Minzdrav of Russia

Email: nrz00009@gmail.com
Junior Research Fellow at the Faboratory of Basic Research in the Field of Regenerative Medicine Krasnodar, Russia

O. M Lyasota

Kuban State University

Email: arcybasheva@mail.ru
PhD Student at the Department of Radiophysics and Nanotechnology Krasnodar, Russia

Yu. V Teterin

Kuban State Medical University of Minzdrav of Russia

Email: valera.chechelian2013@yandex.ru
Third Year Student, Medical Faculty Krasnodar, Russia

References

  1. DeMattos A.M., Olyaei A.J., Prather J.C., Golconda M.S., Barry J.M., Norman D.J. Autosomal-dominant polycystic kidney disease as a risk factor for diabetes mellitus following renal transplantation. Kidney Int. 2005;67(2):714-720.
  2. Abecassis M., Bartlett S.T., Collins A.J., Davis C.L., Delmonico F.L., Friedewald J.J., Hays R., Howard A., Jones E., Leichtman A.B., Merion R.M., Metzger R.A., Pradel F., Schweitzer E.J., Velez R.L., Gaston R.S. Kidney transplantation as primary therapy for endstage renal disease: a National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am SocNephrol. American Society of Nephrology. 2008;3(2): 471-480.
  3. Delmonico F.L., Dew M.A. Living donor kidney transplantation in a global environment. Kidney Int. 2007;71(7):608-614.
  4. Manauis M.N., Pilar K.A., Lesaca R., de Belen Uriarte R., Danguilan R., Ona E. A National Program for Nondirected Kidney Donation From Living Unrelated Donors: The Philippine Experience. Transplant Proc. 2008;40(7):2100-2103.
  5. Fuchs J.R., Nasseri B.A., Vacanti J.P. Tissue engineering: a 21st century solution to surgical reconstruction. Ann Thorac Surg. 2001;72(2):577-591.
  6. Ross E.A., Williams M.J.,Hamazaki T., Terada N., Clapp W.L., Adin C., Ellison G.W., Jorgensen M., Batich C.D. Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. J Am SocNephrol. American Society of Nephrology. 2009;20(11): 2338-2347.
  7. Liu C., Liu S., Xu A., Kang Y., Zheng S., Li H. Preparation of whole-kidney acellular matrix in rats by perfusion. J South Med Univ. 2009;29(5):979-982.
  8. Baptista P.M., Orlando G., Mirmalek-Sani S.H., Siddiqui M., Atala A., Soker S. Whole organ decellularization - a tool for bioscaffold fabrication and organ bioengineering. In: 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE. 2009;6526-6529 p.
  9. Song J.J., Guyette J.P., Gilpin S.E., Gonzalez G., Vacanti J.P., OttH.C. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. Nature Research. 2013;19(5): 646-651.
  10. Fisher J.P., Mikos A.G., Bronzino J.D., Peterson D.R. Tissue engineering : principles and practices. CRC Press. 2013.
  11. Kuevda E.V., Gubareva E.A., Sotnichenko A.S., Gumenyuk I.S., Gilevich I.V., Polyakov I.S. et al. Experience of Perfusion Recellularization of Biological Lung Scaffold in Rats. Russ J Transplantology Artif Organs [Internet]. 2016;18(1):38-44. Available from: http://journal. transpl.ru/vtio/article/view/617.
  12. Gubareva E.A., Sjöqvist S., Gilevich I.V., Sotnichenko A.S., Kuevda E.V., Lim M.L., Feliu N., Lemon G., Danilenko K.A., Nakokhov R.Z., Gumenyuk I.S., Grigoriev T.E., Krasheninnikov S.V., Pokhotko A.G., Basov A.A., Dzhimak S.S., Gustafsson Y., Bautista G., Beltran Rodriguez A., Pokrovsky V.M., Jungebluth P., Chvalun S.N., Holterman M.J., Taylor D.A., Macchiarini P. Orthotopic transplantation of a tissue engineered diaphragm in rats. Biomaterials. Elsevier. 2016;77:320-335.
  13. Basov A.A., Bykov I.M., Baryshev M.G., Dzhimak S.S., Bykov M.I. Determination of deuterium concentration in foods and influence of water with modified isotopic composition on oxidation parameters and heavy hydrogen isotopes content in experimental animals, Vopr. VoprPitan. 2014;83(5):43-50.
  14. Bagaeva V.V., Popova V.M., Pashkova G.S., Isadzhanyan K.E., Nikitin V.V., Zhilenkov E.L. The study the efficacy and safety of antimicrobial agents. Res Pract Med J. 2015;2(3):35.
  15. Badylak S.F., Taylor D., Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. Annual Reviews. 2011;13:27-53.
  16. Wainwright J.M., Czajka C.A., Patel U.B., Freytes D.O., Tobita K., Gilbert T.W., Badylak S.F. Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng Part C Methods. 2010;16(3):525-532.
  17. Sellaro T.L., Ravindra A.K., Stolz D.B., Badylak S.F. Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. Tissue Eng. 2007;13(9): 2301-2310.
  18. Conrad C., Niess H., Huss R., Huber S., von Luettichau I., Nelson P.J., Ott H.C., Jauch K.W., Bruns C.J. Multipotentmesenchymal stem cells acquire a lymphendothelial phenotype and enhance lymphatic regeneration in vivo. Circulation. 2009;119(2):281-289.
  19. Finkel T., Holbrook N.J. Oxidants, oxidative stress and the biology of ageing.Nature. Nature Publishing Group. 2000;408(6809):239-247.
  20. Svistunenko D.A., Davies N., Brealey D., Singer M., Cooper C.E. Mitochondrial dysfunction in patients with severe sepsis: An EPR interrogation of individual respiratory chain components. BiochimBiophysActa - Bioenerg. 2006;1757(4):262-272.
  21. Gubareva E.A., Kuevda E.V., Dzhimak S.S., Basov A.A., Sotnichenko A.S., Bolotin S.N., Gilevich I.V., Gumenyuk I.S., Macchiarini P. EPR spectroscopy solutions for assessment of decellularization of intrathoracic organs and tissues. Dokl Biochem Biophys. 2016;467(1):113-116.
  22. Hulshof F., Schophuizen C., Mihajlovic M., van Blitterswijk C., Masereeuw R., de Boer J., Stamatialis D. New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells. J Tissue EngRegen Med. 2016. doi: 10.1002/ term.2206.
  23. Johnston K.A., Westover A.J., Rojas-Pena A., Buffington D.A., Pino C.J., Smith P.L., Humes H.D. Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS). J Tissue EngRegen Med. 2016. DOI: 10.1002/ term.2206.
  24. Buffington D.A., Pino C.J., Chen L., Westover A.J., Hageman G., Humes H.D. Bioartificial Renal Epithelial Cell System (BRECS): a compact, cryopreservable extracorporeal renal replacement device. Cell Med. 2012;4:33-43.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies