URINARY BLADDER SUBSTITUTION USING COMBINED MEMBRANE BASED ON SECRETIONS OF HUMAN MESENCHYMAL STEM CELLS AND TYPE I COLLAGEN


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Aim. Despite the widespread use of intestinal cystoplasty, urinary bladder substitution remains a challenging problem due to the complexity of operations and the potentially high risk of complications. A promising alternative may be bio-engineered collagen-based matrices containing stem cells or their secretions. Material and methods. To evaluate the effectiveness of this bladder substitution modality, an experiment was conducted on 14 male rabbits. The animals underwent resection of urinary bladder, and the formed defect was substituted with a membrane of type I collagen (series 1, 5 rabbits) or a membrane of the same composition containing a conditioned medium with secretion of mesenchymal stem/stromal cells derived from human adipose tissue (series 2, 5 rabbits). In the comparison group (4 rabbits) resection of the bladder and the closure of the defect was carried out without bladder substitution (series 3). Results. At 1 month after surgery, there was a complete epithelization of the inner surface of the implant, and body tissues replaced the collagen matrix. In series 1, the collagen implant was replaced mainly by connective tissue ingrown with occasional solitary smooth muscle cells. In series 2, the newly formed bladder wall contained numerous smooth muscle cells, growing into the collagen matrix and forming the muscular coat. In series 3, the muscular layer regeneration at the scar site was also noted, but it was less intense, which was confirmed by morphometry. In series 2, more active vascularization of the collagen implant occurred due to neo-angiogenesis, which was more intense than that in series 3, and especially in series 1. Functional studies revealed a reduced bladder functional capacity in series 1 and 3, while in series 2 it was close to normal. During filling cystometry, changes in intra-vesical pressure profile in series 2 were close to normal, while in series 1 and 3 infusion of a small volume of saline resulted in a marked increase in intravesical pressure, showing a reduced compliance of the reconstructed bladder. Discussion The study findings show that implants based on type I collagen can be effectively used to substitute a part of the urinary bladder wall, but bio-engineered collagen matrix grafts containing cell regeneration stimulants secreted by stem cells in their culture medium seem to be more promising.

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作者简介

V. Kirpatovckii

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University; N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology - branch of P. A. Herzen Federal Medical Research Center of Minzdrav of Russia

Email: vladkirp@yandex.ru

D. Kamalov

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University

Email: davidffm@mail.ru

A. Efimenko

Institute for Regenerative Medicine, Medical Scientific Educational Center of M.V. Lomonosov Moscow State University

Email: efimenkoan@gmail.com
PhD, Senior Research Fellow

P. Makarevich

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University

Email: pavel.makarevich@gmail.com

G. Sagaradze

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University; LLC «Gene and Cell Therapy»

Email: georgysagaradze@gmail.com

O. Makarevich

LLC «Gene and Cell Therapy»

Email: go.grigorievaolga@gmail.com

P. Nimiritskii

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University; LLC «Gene and Cell Therapy»

Email: nimiritsky@gmail.com

E. Osidak

LLC «IMTEK»

Email: egorosidak@gmail.com

S. Domogatskii

Russian Cardiology Scientific Industrial Complex of Minzdrav of Russia

Email: spdomo@yandex.ru

V. Karpov

Lomonosov Moscow State University

Email: karpov@fbm.msu.ru
Faculty of Fundamental Medicine

Zh. Akopyan

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University

Email: zhanna.fbm@gmail.com
Faculty of Fundamental Medicine

V. Tkachuk

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University

Email: tkachuk@fbm.msu.ru
Faculty of Fundamental Medicine

A. Kamalov

Medical Scientific Educational Center of M.V. Lomonosov Moscow State University

Email: armais.kamalov@rambler.ru
Faculty of Fundamental Medicine

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