Year 2021 Vol. 29 No 4

SCIENTIFIC PUBLICATIONS
EXPERIMENTAL SURGERY

I.V. MAIBORODIN 1, 2, A.A. SHEVELA 2, S.V. MARCHUKOV 2, V.V. MOROZOV 2, V.A. MATVEEVA 2, V.I. MAIBORODINA 1, A.M NOVIKOV 3, YU.V. TORNUEV 1, B.V. CHURIN 1, A.I. SHEVELA 2

PROLONGATION OF CLEANSING DAMAGED TISSUES FROM DETRITUS USING EXOSOMES OF MULTIPOTENT STROMAL CELLS

Federal Research Center of Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Institute of Molecular Pathology and Pathomorphology 1,
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch 2,
Research Institute of Clinical and Experimental Lymphology 3, Novosibirsk,
The Russian Federation

Objective. To study the effect of exosomes of multipotent mesenchymal stromal cells (EMSCs) on soft tissues damaged during implantation of a metal screw into the bone.
Methods. A defect (2 mm in diameter and 4 mm in depth) was created in the tibial proximal condyles of outbred rabbits. Metal screws were implanted into the defect by preliminary injection of saline (control, n=9 animals) or 19.2 μg of EMSCs per limb (experiment, n=10 rabbits). After 3, 7 and 10 days following the operation, the animals were taken out from the experiment; histological sections of soft tissues from the condyle surface, stained by hematoxylin and eosin were studied using light microscopy.
Results. The use of water cooling in the process of introducing the metal implant into the tibial proximal condyle does not lead to complete removal of small bone fragments, which are subsequently either eliminated outward with wound discharge, or are destroyed and are subjected to lysis by macrophages. As a result of the EMSC effect on soft tissues near the site of damage, the activity of the postoperative inflammation reduces, leads to a slowdown in the resorption of hemorrhages, the elimination of fibrin clots, detritus and small bone fragments. Even on the 10th day after using EMSCs in the postoperative wound a structureless detritus with a small number of infiltrating cells was present, as well as a significant number of multinucleated macrophages with fused cytoplasm, non-viable lysed striated muscle symplasts and bone fragments with a low degree of degradation.
Conclusion. Suppression of inflammation by EMSCs delays the clearance of the postoperative wound, promotes the prolongation of the repair process and the attachment of the granulomatous component to the inflammation. The using EMSCs in the process of intraosseous implantation may be recommended only to control the activity of the inflammatory process and only after maximum preliminary cleansing of the postoperative wound from detritus, including non-viable muscle tissue and bone fragments.

Keywords: damaged tissues, exosomes of multipotent mesenchymal stromal cells, regeneration, inflammation, macrophages
p. 401-411 of the original issue
References
  1. Zigdon-Giladi H, Bick T, Lewinson D, Machtei EE. Mesenchymal stem cells and endothelial progenitor cells stimulate bone regeneration and mineral density. J Periodontol. 2014 Jul;85(7):984-90. doi: 10.1902/jop.2013.130475
  2. Conklin LS, Hanley PJ, Galipeau J, Barrett J, Bollard CM. Intravenous mesenchymal stromal cell therapy for inflammatory bowel disease: Lessons from the acute graft versus host disease experience. Cytotherapy. 2017 Jun;19(6):655-667. doi: 10.1016/j.jcyt.2017.03.006
  3. Bahrami B, Hosseini A, Talei AR, Ghaderi A, Razmkhah M. Adipose derived stem cells exert immunomodulatory effects on natural killer cells in breast cancer. Cell J. 2017 Apr-Jun;19(1):137-45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241510
  4. Abdelhamid L, Hussein H, Ghanem M, Eissa N. Retinoic acid-mediated anti-inflammatory responses in equine immune cells stimulated by LPS and allogeneic mesenchymal stem cells. Res Vet Sci. 2017 Oct;114:225-32. doi: 10.1016/j.rvsc.2017.05.006
  5. Qu M, Yuan X, Liu D, Ma Y, Zhu J, Cui J, Yu M, Li C, Guo D. Bone Marrow-Derived Mesenchymal Stem Cells Attenuate Immune-Mediated Liver Injury and Compromise Virus Control During Acute Hepatitis B Virus Infection in Mice. Stem Cells Dev. 2017 Jun 1;26(11):818-27. doi: 10.1089/scd.2016.0348
  6. Grange C, Tapparo M, Bruno S, Chatterjee D, Quesenberry PJ, Tetta C, Camussi G. Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging. Int J Mol Med. 2014 May;33(5):1055-63. doi: 10.3892/ijmm.2014.1663
  7. Doeppner TR, Herz J, Görgens A, Schlechter J, Ludwig AK, Radtke S, de Miroschedji K, Horn PA, Giebel B, Hermann DM. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Transl Med. 2015 Oct;4(10):1131-43. doi: 10.5966/sctm.2015-0078
  8. Maiborodin IV, Shevela AA, Marchukov SV, Morozov VV, Matveeva VA, Maiborodina VI, Novikov AM, Shevela AI. Regeneration of the bone defect at experimental application of extracellular microvesicles from multipotent stromal cells. Novosti Khirurgii. 2020;28(4):366-69. doi: 10.18484/2305-0047.2020.4.359 (In Russ.)
  9. Blazquez R, Sanchez-Margallo FM, de la Rosa O, Dalemans W, Alvarez V, Tarazona R, Casado JG. Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol. 2014 Nov 4;5:556. doi: 10.3389/fimmu.2014.00556. eCollection 2014.
  10. Zhang S, Chu WC, Lai RC, Lim SK, Hui JH, Toh WS. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage. 2016 Dec;24(12):2135-40. doi: 10.1016/j.joca.2016.06.022
  11. Sun X, Xu M, Cao Q, Huang P, Zhu X, Dong X. A lysosomalK(+) channel regulates large particle phagocytosis by facilitating lysosome Ca(2+) release. Sci Rep. 2020;10(1):1038. doi: 10.1038/s41598-020-57874-2
  12. Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalén M, Jitschin R, Rodin S, Corbascio M, El Andaloussi S, Wiklander OP, Nordin JZ, Skog J, Romain C, Koestler T, Hellgren-Johansson L, Schiller P, Joachimsson PO, Hägglund H, Mattsson M, Lehtiö J, Faridani OR, Sandberg R, Korsgren O, Krampera M, Weiss DJ, Grinnemo KH, Le Blanc K. In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med. 2015 Oct;4(10):1199-213. doi: 10.5966/sctm.2015-0021
  13. Tan JL, Lau SN, Leaw B, Nguyen HPT, Salamonsen LA, Saad MI, Chan ST, Zhu D, Krause M, Kim C, Sievert W, Wallace EM, Lim R. Amnion epithelial cell-derived exosomes restrict lung injury and enhance endogenous lung repair. Stem Cells Transl Med. 2018 Feb;7(2):180-96. doi: 10.1002/sctm.17-0185
  14. Harrell CR, Miloradovic D, Sadikot R, Fellabaum C, Markovic BS, Miloradovic D, Acovic A, Djonov V, Arsenijevic N, Volarevic V. Molecular and cellular mechanisms responsible for beneficial effects of mesenchymal stem cell-derived product “Exo-d-MAPPS” in attenuation of chronic airway inflammation. Anal Cell Pathol (Amst). 2020 Mar 20;2020:3153891. doi: 10.1155/2020/3153891. eCollection 2020.
Address for correspondence:
630090, Russian Federation,
Novosibirsk, Ak. Lavrentyev Avenue, 8,
Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences,
Siberian Branch Center of New Medical Technologies
tel.: +7-913-753-0767
e-mail: imai@mail.ru
Maiborodin Igor V.
Information about the authors:
Maiborodin Igor V., MD, Professor, Chief Researcher of the Laboratory of Cell Biology and Cytology, Institute of Molecular Pathology and Pathomorphology, Federal Research Center for Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Chief Researcher of the Laboratory of Health Management Technologies, Institute of Chemical Biology and Fundamental Medicine of the Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
https://orcid.org/0000-0002-8182-5084
Shevela Aleksandr A., Ph.D, Doctoral Student, the Laboratory of Health Management Technologies, Institute of Chemical Biology and Fundamental Medicine of the Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0001-9235-9384
Marchukov Sergey V., Ph.D, Doctoral Student, the Laboratory of Health Management Technologies, Institute of Chemical Biology and Fundamental Medicine of the Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
https://orcid.org/0000-0002-7381-5820
Morozov Vitaly V., MD, Professor, Head of the Laboratory of Health Management Technologies, Institute of Chemical Biology and Fundamental Medicine of the Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
https://orcid.org/0000-0002-9810-5593
Matveeva Vera A., PhD, Senior Researcher of the Laboratory of Health Management Technologies, Institute of Chemical Biology and Fundamental Medicine of the Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
https://orcid.org/0000-0002-8706-4853
Maiborodina Vitalina I., MD, Leading Researcher, the Laboratory of Ultrastructural Basis of Pathology, Institute of Molecular Pathology and Pathomorphology, Federal ResearchCenter for Fundamental and Translational Medicine of the Ministry of Science and Higher Education of the Russian Federation, Novosibirsk, Russian Federation.
http://orcid.org/0000-0002-5169-6373
Novikov Alexey M., Junior Researcher, the Laboratory of Cell Technology, Institute of Clinical and Experimental Lymphology, the Branch of the Federal State Budgetary Scientific Institution «Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences», The Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0003-1371-7492
Tornuev Yury V., MD (Biol), Professor, Chief Researcher, the Laboratory of General Pathology and Pathomorphology, Institute of Molecular Pathology and Pathomorphology, Federal State Budgetary Scientific Institution «Federal Research Center for Fundamental and Translational Medicine» of the Ministry of Science and Higher Education of the Russian Federation, Novosibirsk, Russian Federation.
http://orcid.org/0000-0001-8629-8909
Churin Boris V., MD, Professor, Chief Researcher, the Laboratory of Cell Biology and Cytology, Institute of Molecular Pathology and Pathomorphology, Federal State Budgetary Scientific Institution «Federal Research Center for Fundamental and Translational Medicine» of the Ministry of Science and Higher Education of the Russian Federation, Novosibirsk, Russian Federation.
http://orcid.org/0000-0001-9742-6152
Shevela Andrey I., MD, Professor, Head of Department “Center of New Medical Technologies”, Institute of Chemical Biology and Fundamental Medicine, The Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0002-3164-9377
Contacts | ©Vitebsk State Medical University, 2007-2023