Possibilities of application of allogenic tissue engineering products in the experimental urinary bladder reconstruction

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Abstract

The article describes the results of an experimental study of tissue-engineering constructions based on lactic acid – poly-L,L-lactide, containing allogeneic cells of various tissue origin. Aim: to show experimentally the possibility of using an allogeneic tissue-engineered graft to replace a defect in the bladder wall.

Material and methods: the study was performed on male Chinchilla rabbits (n=15), which, after resection of the bladder, underwent augmentation cystoplasty with tissue-engineered constructions (TECs) consisting of a polylactide matrix reinforced with silk fibroin and populated with smooth muscle cells with urothelium, fibroblasts, and mesenchymal stem cells.

Results: in 100% of cases of partial bladder replacement with a cell-free matrix or scaffolds containing smooth myocytes with urothelium and fibroblasts, an implant was rejected with a different severity of the inflammatory reaction and a decrease in the capacity of the bladder. Only in the group with mesenchymal stem cells TEC, on the contrary, in 5 cases out of 6 lysis of the matrix occurred, the capacity of the bladders 2,5 months post-surgery was comparable to the preoperative one. At the implantation site, an area of the modified mucous membrane with signs of vascularization was determined. Histologically, the initial stages of reparation and angiogenesis were revealed. With confocal microscopy of cryosections at the implantation site, labeled cells are identified that are involved in the formation of a structure similar to the urothelium.

Conclusion: the effectiveness of mesenchymal stem cells applying as part of a tissue-engineering product for partial replacement of the bladder wall has been shown. There are a number of pathological conditions in urology that require bladder replacement, primarily of a tumor and infectious nature, in which autologous material cannot be used to create a tissue-engineered construction. Such situations dictate necessity for further development of implants using allogeneic cells.

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About the authors

Nadezhda V. Orlova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: nadinbat@gmail.com
ORCID iD: 0000-0002-6572-5956

PhD, senior researcher of the direction "Urology, gynecology and abdominal surgery", urologist

Russian Federation, Ligovsky Ave., 2–4, Saint-Petersburg, 191036

Alexandr N. Muraviov

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; Private University «Saint-Petersburg Medico-Social Institute»

Email: urolog5@gmail.com
ORCID iD: 0000-0002-6974-5305

PhD, Scientific Secretary, Leading Researcher of the direction "Urology, gynecology and abdominal surgery", urologist; Associate Professor of the Department of Surgical Diseases

Russian Federation, Ligovsky Ave., 2–4, Saint-Petersburg, 191036; Kondratievsky Ave., 72, lit. A, 195272, Saint Petersburg

Anna A. Gorelova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; Saint-Petersburg University

Email: gorelova_a@yahoo.com
ORCID iD: 0000-0002-7010-7562

PhD, senior researcher of the direction "Urology, gynecology and abdominal surgery", urologist; assistant performing medical work at the Department of Hospital Surgery

Russian Federation, Ligovsky Ave., 2–4, Saint-Petersburg, 191036; Universitetskaya nab., 7–9, Saint-Petersburg, 199034

Anna N. Remezova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: urolog-remezovaanna@yandex.ru
ORCID iD: 0000-0001-8145-4159

junior researcher of the direction "Urology, gynecology and abdominal surgery", urologist

Russian Federation, Ligovsky Ave., 2–4, Saint-Petersburg, 191036

Tatiana I. Vinogradova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: vinogradova@spbniif.ru
ORCID iD: 0000-0002-5234-349X

PhD, Professor, Chief Researcher

Russian Federation, Ligovsky Ave., 2–4, Saint-Petersburg, 191036

Natalia M. Yudintceva

Institute of Cytology of the Russian Academy of sciences (RAS)

Email: yudintceva@mail.ru
ORCID iD: 0000-0002-7357-1571

PhD, senior researcher

Russian Federation, Tikhoretsky Ave., 4, Saint-Petersburg, 194064

Yulia A. Nashchekina

Institute of Cytology of the Russian Academy of sciences (RAS)

Email: ulychka@mail.ru
ORCID iD: 0000-0002-4371-7445

PhD, researcher

Russian Federation, Tikhoretsky Ave., 4, Saint-Petersburg, 194064

Piotr K. Yablonsky

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; Saint-Petersburg University

Email: glhirurgb2@mail.ru
ORCID iD: 0000-0003-4385-9643

PhD, Professor, Honored Doctor of the Russian Federation, Director; Vice-Rector for Medical Activities

Russian Federation, Ligovsky Ave., 2–4, Saint-Petersburg, 191036; Universitetskaya nab., 7–9, Saint-Petersburg, 199034

References

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Anesthetic bladder capacity of rabbits before intervention and at the time of withdrawal from the experiment (ml)Note: * – the difference in parameters at the beginning and end of the experiment is significant, p<0.05.

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3. Fig. 2. Rabbit bladder on magnetic resonance imaging. Mode t2_tse_tra_320_p2. The suggestive artifact is indicated by an arrow

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4. Fig. 3. Appearance of the TEC implantation site during necropsy: a) The newly formed area of the mucosa is circled with an oval; b) Macropreparation (the inner surface of the bladder). Group 4 (MSK)

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5. Fig. 4. The bladder of a rabbit of the 4th group 2.5 months after the operation. Hematoxylin-eosin stain. ×100

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6. Fig. 5. Confocal microscopy of a cryosection of the bladder wall at the site of implantation: a) – Muscular layer, scale 50 µm; b) – Iron-containing marks in all layers of the MP wall, scale 100 µm; c) – Control. Intact MP wall, scale 100 µm. The lower figure shows an enlarged image of the bladder wall containing labeled cells in its structure, ×20

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