POSSIBILITIES OF APPLICATION OF ALLOGENIC TISSUE ENGINEERING PRODUCTS IN THE EXPERIMENTAL URINARY BLADDER RECONSTRUCTION

DOI: https://doi.org/10.29296/24999490-2022-06-07

N.V. Orlova(1), A.N. Muraviov(1, 2), A.А. Gorelova(1, 3), A.N. Remezova(1), T.I.
Vinogradova(1), N.M. Yudintceva(4), Y.A. Nashchekina(4), P.K. Yablonsky(1, 3)
1-Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation,
Ligovsky Ave., 2–4, Saint-Petersburg, 191036, Russian Federation;
2-Private University «Saint-Petersburg Medico-Social Institute», Kondratievsky Ave., 72, lit. A, 195272, Saint Petersburg, Russian Federation;
3-Saint-Petersburg University, Universitetskaya nab., 7–9, Saint-Petersburg, 199034, Russian Federation;
4-Institute of Cytology of the Russian Academy of sciences (RAS), Tikhoretsky Ave., 4, Saint-Petersburg, 194064, Russian Federation

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.
Keywords: 
allogeneic transplantation, bone marrow mesenchymal stromal cells, bladder, tissue engineering

Список литературы: 
  1. Муравьев А.Н., Орлова Н.В., Блинова М.И., Юдинцева Н.М. Тканевая инженерия в урологии, новые возможности для реконструкции мочевого пузыря. Цитология. 2015; 57 (1): 14–8. [Muravjev A.N., Orlova N.V., Blinova M.I., Yudintseva N.M. Tkanevaya inzheneriya v urologii, novye vozmozhnosti dlya rekonstrukcii mochevogo puzyrya. Citologiya. Tsitologiya. 2015; 57 (1): 14–8 (In Russian)].
  2. Rohrmann D., Albrecht D., Hannappel J., Gerlach R., Schwarzkopp G., Lutzeyer W. Alloplastic replacement of the urinary bladder. J. Urol. 1996; 156: 2094–7.
  3. Семенов С.А., Муравьев А.Н. Влияние хронической задержки мочеиспускания на качество жизни больных туберкулезом мочевого пузыря, перенесших аугментационную илеоцистопластику. Туберкулез и социально значимые заболевания. 2014; 3: 13–8. [Semenov S.A., Muravjev A.N. Vliyanie hronicheskoj zaderzhki mocheispuskaniya na kachestvo zhizni bol'nyh tuberkulezom mochevogo puzyrya, perenesshih augmentacionnuyu ileocistoplastiku. Tuberkulez i social'no znachimye zabolevaniya 2014; 3: 13–8 (In Russian)].
  4. Муравьев А.Н., Зубань О.Н. Роль суправезикального отведения мочи в комплексном лечении больных туберкулезом почек и мочеточников. Урология. 2012; 6: 16–20. [Muravjov A.N., Zuban O.N. Rol supravesikalnogo otvedenija mochi v kompleksnom lechenii bolnih tuberkuljosom pochek I mochetochnikov. Urologiia. 2012; 6: 16–20 (In Russian)].
  5. Горелова А.А., Муравьев А.Н., Виноградова Т.И., Горелов А.И., Юдинцева Н.М., Орлова Н.В., Нащекина Ю.А., Хотин М.Г., Лебедев А.А., Пешков Н.О., Яблонский П.К. Тканеинженерные технологии в реконструкции уретры. Медицинский альянс. 2018; 3: 75–82. [Gorelova A., Muraviov A., Vinogradova T., Gorelov A., Yudintceva N., Orlova N., Nashchekina Y., Khotin M., Lebedev A., Peshkov N., Yablonskiy P. Tissue-engineering technology in urethral reconstruction. Meditsinskii alians. 2018; 3: 75–82 (In Russian)].
  6. Ho M.H., Hou L.T., Tu C.Y, Hsieh H.-J., Lai J.-Y., Chen W.-J., Wang D.-M. Promotion of cell affinity of porous PLLA scaffolds by immobilization of RGD peptides via plasma treatment. Macromol. Biosci. 2006; 6 (1): 90–8. PMID: 16374775. DOI: 10.1002/mabi.200500130.
  7. Shao J., Chen C., Wang Y., Chen X., Du Ch. Early stage structural evolution of PLLA porous scaffolds in thermally induced phase separation process and the corresponding biodegradability and biological property. Polymer Degradation and Stability. 2012; 97: 955–63. DOI: 10.1016/j.polymdegradstab.2012.03.014.
  8. Галкин В.Б., Мушкин А.Ю., Муравьев А.Н., Сердобинцев М.С., Белиловский Е.М., Синицын М.В. Половозрастная структура заболеваемости туберкулезом различных локализаций в Российской Федерации: динамика в XXI в. Туберкулез и болезни легких. 2018; 96 (11): 17–27. [Galkin V.B., Mushkin A.Y., Muraviev A.N., Serdobintsev M.S., Belilovsky E.M., Sinitsyn M.V. The gender and age structure of the incidence of tuberculosis (various localizations) in the Russian Federation: changes over the XXIth century Tuberculosis and Lung Diseases. 2018; 96 (11): 17–26 (In Russian)].
  9. Муравьев А.Н. Суправезикальное отведение мочи в комплексном лечении больных туберкулезом почек и мочеточников: дисс. канд. мед. наук. СПб., 2008; 131. [Muravev A.N. Supravezikalnoe otvedenie mochi v kompleksnom lechenii bolnykh tuberkulezom pochek i mochetochnikov. Dissertation. SPb., 2008; 131 (In Russian)].
  10. Yudintceva N.M., Bogolubova I.O., Muraviov A.N., Sheykhov M.G., Vinogradova T.I., Sokolovich E.G., Samusenko I.A., Shevtsov M.A. Application of the allogenic mesenchymal stem cells in the therapy of the bladder tuberculosis Journal of Tissue Engineering and Regenerative Medicine. 2018; 12 (3): 1580–93.
  11. Yudintceva N.M., Nashchekina Y.A., Blinova M.I., Shevtsov M.A., Orlova N.V., Muraviov A.N., Vinogradova T.I., Sheykhov M.G., Shapkova E.Y., Emeljannikov D.V., Yablonskii P.K., Samusenko I.A., Mikhrina A.L., Pakhomov A.V. Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells. Int. J. Nanomedicine. 2016; 11: 4521–33. DOI: 10.2147/IJN.S111656
  12. Орлова Н.В., Муравьев А.Н., Виноградова Т.И., Блюм Н.М., Семенова Н.Ю., Юдинцева Н.М., Нащекина Ю.А., Блинова М.И., Шевцов М.А., Витовская М.Л., Заболотных Н.В., Шейхов М.Г. Экспериментальная реконструкция мочевого пузыря кролика с использованием аллогенных клеток различного тканевого происхождения. Медицинский альянс. 2016; 1: 49–51. [Orlova N.V., Murav'ev A.N., Vinogradova T.I. , Blyum N.M., Semenova N.Yu., Yudintseva N.M., Nashchekina Yu.A., Blinova M.I., Shevtsov M.A., Vitovskaya M.L.1, Zabolotnykh N.V., Sheikhov M.G. Experimental reconstruction of rabbit bladder using allogeneic cells of different tissue origin. Meditsinskii alians. 2016; 1: 49–51 (In Russian)].