I.V. Maiborodin(1), T.V. Mikheeva(1), S.A. Kuzkin(2), V.I. Maiborodina(2), A.I. Kadyrova(1), A.I. Shevela(1) 1-Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine, Akademika Lavrenteva pr., 8, Novosibirsk, 630090, Russian Federation; 2-Institute of Molecular Pathology and Pathomorphology of the Federal Research Center of Fundamental and Translational Medicine, Akademika Timakova str., 2, Novosibirsk, 630117, Russian Federation E-mail: [email protected]

Introduction. The widespread cellular technologies will sooner or later lead inevitably to the introduction of multipotent mesenchymal stromal cells (MMSC) or their exosomes to patients who have implanted artificial materials in their organism. The engraftment of foreign bodies is accompanied first by the acute and then chronic inflammation, very often acquiring a granulomatous character. A decrease in the activity of the inflammatory response can theoretically improve the results of implantation. Aim. To study the possibility of using autologous MMSC of bone marrow origin (AMMSCBMO) for the influence on the integration process of a silicone implant in the experiment. Methods. The condition of the capsule and tissues around the implanted silicone with adsorbed AMMSCBMO with a transfected GFP-gene and membranes stained by Vybrant® CM Dil was studied by methods of light microscopy with using luminescence. Results. When studying the thickness and vascularization of a capsule formed from dense fibrous connective tissue to delimiting the silicone implanted in the organism, no significant differences were found related to the adsorption of AMMSCBMO on the polymer. AMMSCBMO also do not affect the constriction processes of the capsule around the silicone and its fragmentation. The thickness of the loose fibrous connective tissue around the encapsulated silicone with adsorbed AMMSCBMO less; along with this the capsule contains more blood vessels, compared with the condition after the introduction of the same foreign body, but without the use of cellular technologies. Conclusion. A smaller volume of loose fibrous connective tissue around the implanted silicone with AMMSCBMO indicates a decrease in the activity of the inflammatory response as a result of the use of cellular technologies, more rapid cleansing of the postoperative wound from debris, the success of reparative processes and the creation of conditions for the integration of a foreign body into the organism. It is likely all found effects associated with the presence of AMMSCBMO on silicone after its implantation to be caused not by AMMSCBMO themselves, but by their detritus, which in some cases may have a similar immunomodulatory effect with AMMSCBMO themselves or even exceed it.
multipotent mesenchymal stromal cells, silicone, inflammation, foreign body integration

Список литературы: 
  1. Shree N., Venkategowda S., Venkatranganna M.V., Bhonde R.R. Treatment with adipose derived mesenchymal stem cells and their conditioned media reverse carrageenan induced paw oedema in db/db mice. Biomed. Pharmacother. 2017; 90: 350–3.
  2. Jackson M.V., Krasnodembskaya A.D. Analysis of mitochondrial transfer in direct co-cultures of human monocyte-derived macrophages (MDM) and mesenchymal stem cells (MSC). Bio Protoc. 2017; 7 (9): pii: e2255.
  3. Qiu G., Zheng G., Ge M., Huang L., Tong H., Chen P. et al. Adipose-derived mesenchymal stem cells modulate CD14(++)CD16(+) expression on monocytes from sepsis patients in vitro via prostaglandin E2. Stem Cell. Res. Ther. 2017; 8 (1): 97.
  4. Tang X.D., Shi L., Monsel A., Li X.Y., Zhu H.L., Zhu Y.G., Qu J.M. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang-1 mRNA. Stem Cells. 2017; 35 (7): 1849–59.
  5. Robinson A.M., Rahman A.A., Miller S., Stavely R., Sakkal S., Nurgali K. The neuroprotective effects of human bone marrow mesenchymal stem cells are dose-dependent in TNBS colitis. Stem Cell. Res. Ther. 2017; 8 (1): 87.
  6. Takeyama H., Mizushima T., Uemura M., Haraguchi N., Nishimura J., Hata T. et al. Adipose-derived stem cells ameliorate experimental murine colitis via tsp-1-dependent activation of latent TGF-β. Dig. Dis. Sci. 2017; 62 (8): 1963–74.
  7. Майбородин И.В., Морозов В.В., Аникеев А.А., Фигуренко Н.Ф., Маслов Р.В., Частикин Г.А., Матвеева В.А., Майбородина В.И. Макрофагальный ответ у крыс на введение мультипотентных мезенхимальных стромальных клеток в регион хирургической травмы. Новости хирургии. 2017; 25 (3): 233–41.
  8. [Maiborodin I.V., Morozov V.V., Anikeev A.A., Figurenko N.F., Maslov R.V., Chastikin G.A., Matveeva V.A., Maiborodina V.I. Macrophage reaction to multipotent mesenchymal stromal cells introduction into surgical trauma site in rats. Novosti Khirurgii. 2017; 25 (3): 233–41 (in Russian)]
  9. Майбородин И.В., Маслов Р.В., Михеева Т.В., Еловский А.А., Фигуренко Н.Ф., Майбородина В.И., Шевела А.И., Анищенко В.В. Макрофагальная адсорбция мультипотентных мезенхимальных стромальных клеток как доказательство их миграции по сосудам после тканевой инъекции. Молекулярная медицина. 2018; 16 (4): 56–61.
  10. [Maiborodin I.V., Maslov R.V., Mikheeva T.V., Elovskiy A.A., Figurenko N.F., Maiborodina V.I., Shevela A.I., Anishchenko V.V. Macrophagal adsorption of multipotent mesenchymal stromal cells and their debris from vascular bed proves the migration of these cellular elements through the vessels after tissue injection. Molekulyarnaya meditsina. 2018; 16 (3): 56–61 (in Russian)]
  11. Крымский Л. Д., Нестайко Г. В., Рыбалов А. В. Растровая электронная микроскопия сосудов и крови. М.: Медицина, 1976; 168.
  12. [Krymskij L.D., Nestajko G.V., Rybalov A.V. Rastrovaja jelektronnaja mikroskopija sosudov i krovi [Raster electron microscopy of vessels and blood]. M.: Medicina, 1976; 168 (in Russian)].
  13. Волкова О. В., Шахламов В. А., Миронов А. А. Атлас сканирующей электронной микроскопии клеток, тканей и органов. М.: Медицина, 1987; 464.
  14. [Volkova O.V., Shahlamov V.A., Mironov A.A. Atlas skanirujushhej jelektronnoj mikroskopii kletok, tkanej i organov [Atlas of the scanning electron microscopy of cells, tissues and organs]. M.: Medicina, 1987; 464 (in Russian)]
  15. Head J.R., Seeling L.L. Jr. Lymphatic vessels in the uterine endometrium of virgin rats. J. Reprod. Immunol. 1984; 6 (3): 157–66.
  16. Шевела А.А., Тодер М.С., Матвеева В.А., Артемьева Л.В., Матвеев А.Л., Мейснер С.Н., Мейснер Л.Л., Шевела А.И., Аникеев А.А., Фигуренко Н.Ф., Маслов Р.В., Байбородин С.И., Майбородин И.В. Химически чистое кремниевое и танталовое покрытие не токсично для мезенхимальных стромальных клеток и усиливает цитосовместимость электрополированного сплава никелида титана. Вопросы реконструктивной и пластической хирургии. 2017; 20 (3(62)): 45–50.
  17. [Shevela A.A., Toder M.S., Matveeva V.A., Artemeva L.V., Matveev A.L., Meisner S.N., Meisner L.L., Shevela А.I., Anikeev A.A., Figurenko N.F., Maslov R.V., Bayborodin S.I., Maiborodin I.V. Chemically pure silicon and titanium coating is not toxic for mesenchymal stromal cells and improves cytological compatibility of electropolished TiNi alloy. Issues of Reconstructive and Plastic Surgery. 2017; 20 (3(62)): 45–50 (in Russian)]
  18. Lei L., Tzekov R., Tang S., Kaushal S. Accumulation and autofluorescence of phagocytized rod outer segment material in macrophages and microglial cells. Mol Vis. 2012; 18: 103–13.
  19. Potter K.A., Simon J.S., Velagapudi B., Capadona J.R. Reduction of autofluorescence at the microelectrode-cortical tissue interface improves antibody detection. J. Neurosci. Methods. 2012; 203 (1): 96–105.
  20. Liu S., Jiang L., Li H., Shi H., Luo H., Zhang Y., Yu C., Jin Y. Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis. J. Invest Dermatol. 2014; 134 (10): 2648–57.
  21. Yates C.C., Nuschke A., Rodrigues M., Whaley D., Dechant J.J., Taylor D.P., Wells A. Improved transplanted stem cell survival in a polymer gel supplemented with tenascin C accelerates healing and reduces scarring of murine skin wounds. Cell Transplant. 2017; 26 (1): 103–13.
  22. Conklin L.S., Hanley P.J., Galipeau J., Barrett J., Bollard C.M. Intravenous mesenchymal stromal cell therapy for inflammatory bowel disease: Lessons from the acute graft versus host disease experience. Cytotherapy. 2017; 19 (6): 655–67.
  23. Carty F., Mahon B.P., English K. The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents? Clin. Exp. Immunol. 2017; 188 (1): 1–11.
  24. Amouzegar A., Mittal S.K., Sahu A., Sahu S.K., Chauhan S.K. Mesenchymal stem cells modulate differentiation of myeloid progenitor cells during inflammation. Stem Cells. 2017; 35 (6): 1532–41.
  25. Xiao J., Yang R., Biswas S., Zhu Y., Qin X., Zhang M. et al. Neural stem cell-based regenerative approaches for the treatment of multiple sclerosis. Mol. Neurobiol. 2018; 55 (4): 3152–71.
  26. Cronce M.J., Faulknor R.A., Pomerantseva I., Liu X.H., Goldman S.M., Ekwueme E.C., Mwizerwa O., Neville C.M., Sundback C.A. In vivo response to decellularized mesothelium scaffolds. J. Biomed Mater Res B Appl Biomater. 2018; 106 (2): 716–25.
  27. Segreto F., Carotti S., Marangi G.F., Tosi D., Zingariello M., Pendolino A.L., Sancillo L., Morini S., Persichetti P. The role of angiogenesis, inflammation and estrogen receptors in breast implant capsules development and remodeling. J Plast Reconstr Aesthet Surg. 2018; 71 (5): 637–43.
  28. Truong T., Jones K.S. Capsaicin reduces PLGA-induced fibrosis by promoting M2 macrophages and suppressing overall inflammatory Response. J. Biomed Mater Res A. 2018; 106 (9): 2424–32.
  29. Майбородин И.В., Шевела А.И., Морозов В.В., Новикова Я.В., Матвеева В.А., Дровосеков М.Н., Баранник М.И. Реакция тканей крыс на имплантацию полигидроксиалканоата в состоянии пленок и ультратонких волокон. Бюллетень экспериментальной биологии и медицины. 2012; 154 (9): 365–70.
  30. [Maiborodin I.V., Shevela A.I., Morozov V.V., Novikova Ya.V., Matveeva V.A., Drovosekov M.N., Barannik M.I. Reaction of the rat tissues to implantation of polyhydroxyalkanoate films and ultrafine fibers. Bulletin of Experimental Biology and Medicine. 2013; 154 (3): 379–84 (in Russian)]
  31. Майбородин И.В., Кузнецова И.В., Береговой Е.А., Шевела А.И., Баранник М.И., Майбородина В.И., Манаев А.А. Реакция тканей крыс на имплантацию биодеградируемого полимера на основе молочной кислоты. Бюллетень экспериментальной биологии и медицины. 2013;156(12):848-853.
  32. [Maiborodin I.V., Kuznetsova I.V., Beregovoi E.A., Shevela A.I., Barannik M.I., Maiborodina V.I., Manaev A.A. Reaction of rat tissues to implantation of lactic acid-based biodegradable polymer. Bulletin of Experimental Biology and Medicine. 2014; 156 (6): 874–9. (in Russian)]
  33. Кузнецова И.В., Майбородин И.В., Шевела А.И., Баранник М.И., Манаев А.А., Бромбин А.И., Майбородина В.И. Реакция окружающих тканей на имплантацию абсорбируемых шовных материалов. Бюллетень экспериментальной биологии и медицины. 2014; 157 (3): 375–80.
  34. [Kuznetsova I.V., Maiborodin I.V., Shevela A.I., Barannik M.I., Manaev A.A., Brombin A.I., Maiborodina V.I. Local Tissue Reaction to Implantation of Biodegradable Suture Materials. Bulletin of Experimental Biology and Medicine. 2014; 157 (3): 390–4. (in Russian)]
  35. Майбородин И.В., Якимова Н.В., Матвеева В.А., Пекарев О.Г., Майбородина Е.И., Пекарева Е.О. Ангиогенез в рубце матки крыс после введения аутологичных мезенхимальных стволовых клеток костномозгового происхождения. Бюллетень экспериментальной биологии и медицины. 2010; 150 (12): 705–11.
  36. [Maiborodin I.V., Yakimova N.V., Matveyeva V.A., Pekarev O.G., Maiborodina E.I., Pekareva E.O. Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells. Bull Exp. Biol. Med. 2011; 150 (6): 756–61 (in Russian)].
  37. Майбородин И.В., Оноприенко Н.В., Частикин Г.А. Морфологические изменения тканей матки крыс и возможность самопроизвольных родов в результате введения мультипотентных мезенхимных стромальных клеток на фоне гидрометры. Бюллетень экспериментальной биологии и медицины. 2015; 159 (4): 511–6.
  38. [Maiborodin I.V., Onoprienko N.V., Chastikin G.A. Morphological changes in rat uterine tissues and possibility of spontaneous labor as a result of injection of multipotent mesenchymal stromal cells against the background of hydrometra. Bulletin of Experimental Biology and Medicine. 2015; 159 (4): 511–6. (in Russian)]
  39. Майбородин И.В., Шевела А.И., Матвеева В.А., Дровосеков М.Н., Баранник М.И., Кузнецова И.В. Ангиогенез в грануляционной ткани после имплантации полигидроксиалканоата с мезенхимальными стволовыми клетками. Новости хирургии. 2013; 21 (2): 29–36.
  40. [Maiborodin I.V., Shevela A.I., Matveeva V.A., Drovosekov M.N., Barannick M.I., Kuznetsova I.V. Angiogenesis in granulation tissue after implantation of polyhydroxyalkanoate with mesenchymal stem cells. Novosti Khirurgii. 2013; 21 (2): 29–36 (in Russian)].