mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-4-515-522mimmun-1559Research ArticleОБЗОРЫREVIEWSРОЛЬ МЕЗЕНХИМАЛЬНЫХ МУЛЬТИПОТЕНТНЫХ СТРОМАЛЬНЫХ КЛЕТОК В РЕМОДЕЛИРОВАНИИ КОСТНОЙ ТКАНИROLE OF MESENCHYMAL MULTIPOTENT STROMAL CELLS IN REMODELING OF BONE DEFECTSКиселевскийМ. В.KiselevskyM. V.

д.м.н., профессор, заведующий лабораторией клеточного иммунитета,

115478, Москва, Каширское шоссе, 24

PhD, MD (Medicine), Professor, Head, Laboratory of Cellular Immunity,

115478, Moscow, Kashirskoe highway, 24

kisele@inbox.ruАнисимоваН. Ю.AnisimovaN. Yu.

д.б.н., ведущий научный сотрудник лаборатории клеточного иммунитета;

научный сотрудник центра композиционных материалов,

Москва

PhD, MD (Biology), Leading Research Associate, Laboratory of Cellular Immunity;

Research Associate, Center for Composite Materials,

Moscow

ДолжиковаЮ. И.DolzhikovaYu. I.

инженер центра композиционных материалов,

Москва

Engineer, Center for Composite Materials,

Moscow

ВласенкоР. Я.VlasenkoR. Ya.

к.м.н., старший научный сотрудник лаборатории клеточного иммунитета,

Москва

PhD (Medicine), Senior Research Associate, Laboratory of Cellular Immunity,

Moscow

СенатовФ. С.SenatovF. S.

к.ф-м.н., научный сотрудник центра композиционных материалов,

Москва

PhD (Physics and Mathematics), Research Associate, Center for Composite Materials,

Moscow

КарауловА. В.KaraulovA. V.

д.м.н., профессор, академик РАН, заведующий кафедрой клинической иммунологии и аллергологии,

Москва

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Head, Department of Clinical Immunology and Allergology,

Moscow

ФГБНУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения РФРоссияN.N. Blokhin National Medical Center of OncologyRussian FederationФГБНУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения РФ; Национальный технический университет «МИСиС»РоссияN.N. Blokhin National Medical Center of Oncology; National University of Science and Technology MISiSRussian FederationНациональный технический университет «МИСиС»РоссияNational University of Science and Technology MISiSRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation201825062018204515522Copyright © Киселевский М.В., Анисимова Н.Ю., Должикова Ю.И., Власенко Р.Я., Сенатов Ф.С., Караулов А.В., 20182018Киселевский М.В., Анисимова Н.Ю., Должикова Ю.И., Власенко Р.Я., Сенатов Ф.С., Караулов А.В.Kiselevsky M.V., Anisimova N.Y., Dolzhikova Y.I., Vlasenko R.Y., Senatov F.S., Karaulov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1559

Способность мезенхимальных мультипотентных стромальных клеток (МСК) дифференцироваться в несколько видов мезенхимальных тканей делает эти клетки основными кандидатами для создания тканеинженерных конструкций для регенеративной медицины. МСК способствуют интеграции биоимплантата с нативной костью и стимулируют процесс остеогенеза, но также обладают иммуномодулирующими свойствами, контролируя воспалительные реакции и модифицируя иммунные клетки. МСК влияют не только на иммунный ответ организма, препятствуя реакции иммунологического отторжения имплантированных тканеинженерных конструкций, но могут также оказывать воздействие на иммунные реакции костной ткани. MСК играют важную роль в регенерации кости, регулируя образования остеобластов и подавляя активность эффекторов воспаления и остекластогенез. Доклинические и первые клинические испытания биоимплантатов кости, заселенных МСК, свидетельствуют о перспективности данной стратегии получения тканеинженерных конструкций для регенерации костей.

Ability of mesenchymal multipotent stromal cells (MSCs) to differentiate into several types of mesenchymal tissues allows to consider these cells the main candidates for creating tissue engineering constructions for regenerative medicine. MSCs promote integration of bio-implants into the native bone and stimulate osteogenesis. MSCs are characterized by immunomodulatory properties, due to inflammation control and modification of immune cells. MSCs affect not only the in vivo immune response by preventing immunological rejection of implanted tissue engineering designs, but it can also influence the bone tissue immunity. MSCs play an important role in bone regeneration, by regulating the osteoblastic generation, and suppressing activity of inflammation effectors and osteoclastogenesis. Some pre-clinical and first clinical trials of bone bio-implants colonized with MSC, demonstrate promising outlooks for this strategy in order to obtain tissue engineering constructions for bone regeneration.

мезенхимальные мультипотентные стромальные клеткииммуномодулирующая активностьбиоимплантаты костейостеоиммунологиятканеинженерные конструкцииmesenchymal multipotent stromal cellsimmunomodulating activitybone bioimplantsosteoimmunologytissue engineering constructionsReferencesКиселевский М.В., Анисимова Н.Ю., Корнюшенков Е.А., Шепелев А.Д., Чвалун С.Н., Полоцкий Б.Е., Давыдов М.И. Биосовместимые синтетические матриксы трахеи на основе полимерных ультраволокнистых материалов, колонизированные мезенхимальными мультипотентными клетками // Современные технологии в медицине, 2016. Т. 8, № 1. C. 7-13. [Kiselevsky M.V., Anisimova N.Yu., Kornushenkov E.A., Shepelev A.D., Chvalun S.N., Polotsky B.E., Davydov M.I. Biocompatible synthetic tracheal matrices based on polymer. Sovremennye tekhnologii v meditsine = Modern Technologies in Medicine, 2016, Vol. 8, no. 1, pp. 7-13. (In Russ.)]Киселевский М.В., Анисимова Н.Ю., Корнюшенков Е.А., Шепелев А.Д., Чвалун С.Н., Полоцкий Б.Е., Давыдов М.И. Биосовместимые синтетические матриксы трахеи на основе полимерных ультраволокнистых материалов, колонизированные мезенхимальными мультипотентными клетками // Современные технологии в медицине, 2016. Т. 8, № 1. C. 7-13. [Kiselevsky M.V., Anisimova N.Yu., Kornushenkov E.A., Shepelev A.D., Chvalun S.N., Polotsky B.E., Davydov M.I. Biocompatible synthetic tracheal matrices based on polymer. Sovremennye tekhnologii v meditsine = Modern Technologies in Medicine, 2016, Vol. 8, no. 1, pp. 7-13. (In Russ.)]Климович В.Б. Иммуномодулирующая активность мезенхимальных стромальных (стволовых) клеток // Медицинская иммунология, 2014. T. 16, № 2. С. 107-126. [Klimovich V.B. Immunomodulatory activity of mesenchimal stromal (stem) cells. Meditsinskaya immunologiya = Medical Immunology (Russia), 2014, Vol. 16, no. 2, pp. 107-126. (In Russ.)] doi: 10.15789/1563-0625-2014-2-107-12.Климович В.Б. Иммуномодулирующая активность мезенхимальных стромальных (стволовых) клеток // Медицинская иммунология, 2014. T. 16, № 2. С. 107-126. [Klimovich V.B. Immunomodulatory activity of mesenchimal stromal (stem) cells. Meditsinskaya immunologiya = Medical Immunology (Russia), 2014, Vol. 16, no. 2, pp. 107-126. (In Russ.)] doi: 10.15789/1563-0625-2014-2-107-12.Alcayaga-Miranda F., Cuenca. J,. Martin A., Contreras L., Figueroa F.E., Khour M. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Stem Cell Res. Ther., 2015, Vol. 6, no. 6, p. 199.Alcayaga-Miranda F., Cuenca. J,. Martin A., Contreras L., Figueroa F.E., Khour M. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Stem Cell Res. Ther., 2015, Vol. 6, no. 6, p. 199.Arck P.C., Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring’s health. Nat. Med., 2013, Vol. 19, no. 5, pp. 548-556.Arck P.C., Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring’s health. Nat. Med., 2013, Vol. 19, no. 5, pp. 548-556.Aubin J. Regulation of osteoblast formation and function. Rev. Endocrinol. Metab. Disord., 2001, Vol. 2, no. 1, pp. 81-94.Aubin J. Regulation of osteoblast formation and function. Rev. Endocrinol. Metab. Disord., 2001, Vol. 2, no. 1, pp. 81-94.Bianco P., Cao X., Frenette P.S., Mao J.J., Robey, P.G., Simmons P.J., Wang C.Y. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat. Med., 2013, Vol. 19, no. 1, pp. 35-42.Bianco P., Cao X., Frenette P.S., Mao J.J., Robey, P.G., Simmons P.J., Wang C.Y. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat. Med., 2013, Vol. 19, no. 1, pp. 35-42.Brandau S., Jakob M., Bruderek K., Bootz F., Giebel B., Radtke S., Mauel K., Jäger M., Flohé S.B., Lang S. Mesenchymal stem cells augment the anti-bacterial activity of neutrophil granulocytes. PLoS ONE, 2014, Vol. 9, e106903. doi: 10.1371/journal.pone.0106903.Brandau S., Jakob M., Bruderek K., Bootz F., Giebel B., Radtke S., Mauel K., Jäger M., Flohé S.B., Lang S. Mesenchymal stem cells augment the anti-bacterial activity of neutrophil granulocytes. PLoS ONE, 2014, Vol. 9, e106903. doi: 10.1371/journal.pone.0106903.Bunpetch V., Wu H., Zhang S., Ouyang H.W. From “bench to bedside”: current advancement on large-scale production of mesenchymal stem cells. Stem Cells Dev., 2017, Vol. 26, no. 9, pp. 1662-1673.Bunpetch V., Wu H., Zhang S., Ouyang H.W. From “bench to bedside”: current advancement on large-scale production of mesenchymal stem cells. Stem Cells Dev., 2017, Vol. 26, no. 9, pp. 1662-1673.Carty F., Mahon B.P., English K. The influence of macrophages on mesenchymal stromal cell therapy: Passive or aggressive agents? Clin. Exp. Immunol., 2012, Vol. 188, no. 1, pp. 1-11.Carty F., Mahon B.P., English K. The influence of macrophages on mesenchymal stromal cell therapy: Passive or aggressive agents? Clin. Exp. Immunol., 2012, Vol. 188, no. 1, pp. 1-11.Cerdeira A.S., Rajakumar A., Royle C.M., Lo A., Husain Z., Thadhani R.I., Sukhatme V.P., Karumanchi S.A., Kopcow H.D. Conversion of peripheral blood NK cells to a decidual NK-like phenotype by a cocktail of defined factors. J. Immunol., 2013, Vol. 190, no. 8, pp. 3939-3948.Cerdeira A.S., Rajakumar A., Royle C.M., Lo A., Husain Z., Thadhani R.I., Sukhatme V.P., Karumanchi S.A., Kopcow H.D. Conversion of peripheral blood NK cells to a decidual NK-like phenotype by a cocktail of defined factors. J. Immunol., 2013, Vol. 190, no. 8, pp. 3939-3948.Chena F-M., Liu X. Advancing biomaterials of human origin for tissue engineering. Prog. Polym. Sci., 2016. Vol. 53, no. 1, pp. 86-168.Chena F-M., Liu X. Advancing biomaterials of human origin for tissue engineering. Prog. Polym. Sci., 2016. Vol. 53, no. 1, pp. 86-168.Cheng J., Liu J., Shi Z., Jules J., Xu D., Luo S., Wei S., Feng X. Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis. J. Interferon Cytokine Res., 2012, Vol. 32, no. 1, pp. 34-45.Cheng J., Liu J., Shi Z., Jules J., Xu D., Luo S., Wei S., Feng X. Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis. J. Interferon Cytokine Res., 2012, Vol. 32, no. 1, pp. 34-45.Croes M., Oner F.C., Kruyt M.C., Blokhuis T.J., Bastian O., Dhert W.J., Alblas J. Proinflammatory mediators enhance the osteogenesis of human mesenchymal stem cells after lineage commitment. PloS ONE, 2015, Vol. 10, no. 7, e0132781. doi: 10.1371/journal.pone.0132781.Croes M., Oner F.C., Kruyt M.C., Blokhuis T.J., Bastian O., Dhert W.J., Alblas J. Proinflammatory mediators enhance the osteogenesis of human mesenchymal stem cells after lineage commitment. PloS ONE, 2015, Vol. 10, no. 7, e0132781. doi: 10.1371/journal.pone.0132781.Сornish J., Gillespi M.T., Callon K.E., Horwood N.J., Moseley J.M., Reid I.R. Interleukin-18 is a novel mitogen of osteogenic and chondrogenic cells. Endocrinology, 2005, Vol. 144, no. 4, pp. 1194-1201.Сornish J., Gillespi M.T., Callon K.E., Horwood N.J., Moseley J.M., Reid I.R. Interleukin-18 is a novel mitogen of osteogenic and chondrogenic cells. Endocrinology, 2005, Vol. 144, no. 4, pp. 1194-1201.Dawson J.I., Oreffo R.O. Bridging the regeneration gap: stem cells, biomaterials and clinical translation in bone tissue engineering. Arch. Biochem. Biophys., 2008, Vol. 473, no. 2, pp. 124-131.Dawson J.I., Oreffo R.O. Bridging the regeneration gap: stem cells, biomaterials and clinical translation in bone tissue engineering. Arch. Biochem. Biophys., 2008, Vol. 473, no. 2, pp. 124-131.Dayan V., Yannarelli G., Billia F., Filomeno P., Wang X.H., Davies J.E., Keating A. Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction. Basic Res. Cardiol., 2011, Vol. 106, no. 6, pp. 1299-1310.Dayan V., Yannarelli G., Billia F., Filomeno P., Wang X.H., Davies J.E., Keating A. Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction. Basic Res. Cardiol., 2011, Vol. 106, no. 6, pp. 1299-1310.Discher D.E., Mooney D.J., Zandstra P.W. Growth factors, matrices, and forces combine and control stem cells. Science, 2009, Vol. 324, no. 5935, pp. 1673-1677.Discher D.E., Mooney D.J., Zandstra P.W. Growth factors, matrices, and forces combine and control stem cells. Science, 2009, Vol. 324, no. 5935, pp. 1673-1677.Eggenhofer E., Hoogduijn M.J. Mesenchymal stem cell-educated macrophages. Transplant. Res., 2012, Vol. 1, no. 1, pp. 1-12.Eggenhofer E., Hoogduijn M.J. Mesenchymal stem cell-educated macrophages. Transplant. Res., 2012, Vol. 1, no. 1, pp. 1-12.Feinberg A.W. Engineered tissue grafts: opportunities and challenges in regenerative medicine. Wiley Interdiscip. Rev. Syst. Biol. Med., 2012, Vol. 4, no. 2, pp. 207-220.Feinberg A.W. Engineered tissue grafts: opportunities and challenges in regenerative medicine. Wiley Interdiscip. Rev. Syst. Biol. Med., 2012, Vol. 4, no. 2, pp. 207-220.Fisher M.B., Mauck R.L. Tissue engineering and regenerative medicine: recent innovations and the transition to translation. Tissue Eng. Part B Rev., 2013, Vol. 19, no. 1, pp. 1-13.Fisher M.B., Mauck R.L. Tissue engineering and regenerative medicine: recent innovations and the transition to translation. Tissue Eng. Part B Rev., 2013, Vol. 19, no. 1, pp. 1-13.Galland S., Vuille J., Martin P., Letovanec I. Tumor-derived mesenchymal stem cells use distinct mechanisms to block the activity of natural killer cell subsets. Cell Rep., 2017, Vol. 20, no. 12, pp. 2891-2905.Galland S., Vuille J., Martin P., Letovanec I. Tumor-derived mesenchymal stem cells use distinct mechanisms to block the activity of natural killer cell subsets. Cell Rep., 2017, Vol. 20, no. 12, pp. 2891-2905.Gao F., Chiu S.M., Motan D.A., Zhang Z., Chen L., Ji H.L., Zhang Z., Chen L., Ji H.L., Tse H.F., Fu Q.L., Lian Q. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis., 2016, Vol. 21, no. 7, e2062. doi: 10.1038/cddis.2015.327.Gao F., Chiu S.M., Motan D.A., Zhang Z., Chen L., Ji H.L., Zhang Z., Chen L., Ji H.L., Tse H.F., Fu Q.L., Lian Q. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis., 2016, Vol. 21, no. 7, e2062. doi: 10.1038/cddis.2015.327.Griffith L.G., Naughton G. Tissue engineering – current challenges and expanding opportunities. Science, 2002, Vol. 295, no. 5556, pp. 1009-1014.Griffith L.G., Naughton G. Tissue engineering – current challenges and expanding opportunities. Science, 2002, Vol. 295, no. 5556, pp. 1009-1014.Guarino V., Causa F., Ambrosio L. Bioactive scaffolds for bone and ligament tissue. Expert. Rev. Med. Devices, 2007, Vol. 4, no. 3, pp. 405-418.Guarino V., Causa F., Ambrosio L. Bioactive scaffolds for bone and ligament tissue. Expert. Rev. Med. Devices, 2007, Vol. 4, no. 3, pp. 405-418.Hanker J.S., Giammara B.L. Biomaterials and biomedical devices. Science, 1988, Vol. 242, no. 4880, pp. 885-892.Hanker J.S., Giammara B.L. Biomaterials and biomedical devices. Science, 1988, Vol. 242, no. 4880, pp. 885-892.Hanson S., D’Souza R.N., Hematti P. Biomaterial-mesenchymal stem cell constructs for immunomodulation in composite tissue engineering. Tissue Eng. Part A, 2014, Vol. 20, no. 15-16, pp. 2162-2168.Hanson S., D’Souza R.N., Hematti P. Biomaterial-mesenchymal stem cell constructs for immunomodulation in composite tissue engineering. Tissue Eng. Part A, 2014, Vol. 20, no. 15-16, pp. 2162-2168.Hardy J.G., Villancio-Wolter M.K., Sukhavasi R.C., Mouser D.J., Aguilar D. Jr, Geissler S.A., Kaplan D.L., Schmidt C.E. Electrical stimulation of human mesenchymal stem cells on conductive nanofibers enhances their differentiation toward osteogenic outcomes. Macromolecular Rapid Communications, 2015, Vol. 36, no. 1, pp. 1884-1890.Hardy J.G., Villancio-Wolter M.K., Sukhavasi R.C., Mouser D.J., Aguilar D. Jr, Geissler S.A., Kaplan D.L., Schmidt C.E. Electrical stimulation of human mesenchymal stem cells on conductive nanofibers enhances their differentiation toward osteogenic outcomes. Macromolecular Rapid Communications, 2015, Vol. 36, no. 1, pp. 1884-1890.Harrison R.H., St-Pierre J.P., Stevens M.M. Tissue engineering and regenerative medicine: a year in review. Tissue Eng. Part B Rev., 2014, Vol. 20, no. 1, pp. 1-16.Harrison R.H., St-Pierre J.P., Stevens M.M. Tissue engineering and regenerative medicine: a year in review. Tissue Eng. Part B Rev., 2014, Vol. 20, no. 1, pp. 1-16.Liu D., Yi C., Fong C.C., Jin Q., Wang Z., Yu W.K., Sun D., Zhao J., Yang M. Activation of multiple signaling pathways during the differentiation of mesenchymal stem cells cultured in a silicon nanowire microenvironment. Nanomed, 2014, Vol. 10, no. 6, pp. 1153-1163.Liu D., Yi C., Fong C.C., Jin Q., Wang Z., Yu W.K., Sun D., Zhao J., Yang M. Activation of multiple signaling pathways during the differentiation of mesenchymal stem cells cultured in a silicon nanowire microenvironment. Nanomed, 2014, Vol. 10, no. 6, pp. 1153-1163.Johnson V., Webb T., Norman A., Coy J., Kurihara J., Regan D., Dow S. Activated mesenchymal stem cells interact with antibiotics and host innate immune responses to control chronic bacterial infections. Sci. Rep., 2017, Vol. 7, no. 1, p. 9575.Johnson V., Webb T., Norman A., Coy J., Kurihara J., Regan D., Dow S. Activated mesenchymal stem cells interact with antibiotics and host innate immune responses to control chronic bacterial infections. Sci. Rep., 2017, Vol. 7, no. 1, p. 9575.Katagiri W., Osugi M., Kawai T., Hibi H. First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head Face Med., 2016, Vol. 12, no. 5, pp. 1-10.Katagiri W., Osugi M., Kawai T., Hibi H. First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head Face Med., 2016, Vol. 12, no. 5, pp. 1-10.Kiernan C.H., Wolvius E.B., Brama P.A.J., Farrell E. The immune response to allogeneic differentiated mesenchymal stem cells in the context of bone tissue engineering. Tissue Eng. Part B Rev., 2018, Vol. 24, no. 1, pp. 75-83.Kiernan C.H., Wolvius E.B., Brama P.A.J., Farrell E. The immune response to allogeneic differentiated mesenchymal stem cells in the context of bone tissue engineering. Tissue Eng. Part B Rev., 2018, Vol. 24, no. 1, pp. 75-83.Krasnodembskaya A., Song Y., Fang X., Gupta N., Serikov V., Lee J.W., Matthay M.A. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells, 2010, Vol. 28, no. 25, pp. 2229-2238.Krasnodembskaya A., Song Y., Fang X., Gupta N., Serikov V., Lee J.W., Matthay M.A. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells, 2010, Vol. 28, no. 25, pp. 2229-2238.Lee K., Silva E.A., Mooney D.J. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J. R. Soc. Interface, 2011, Vol. 8, no. 55, pp. 153-170.Lee K., Silva E.A., Mooney D.J. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J. R. Soc. Interface, 2011, Vol. 8, no. 55, pp. 153-170.Li M., Hasegawa T., Hogo H., Tatsumi S., Liu Z., Guo Y., Sasaki M., Tabata C., Yamamoto T., Ikeda K., Amizuka N. Histological examination on osteoblastic activities in the alveolar bone of transgenic mice with induced ablation of osteocytes. Histol. Histopathol., 2013, Vol. 28, no. 3, pp. 327-335.Li M., Hasegawa T., Hogo H., Tatsumi S., Liu Z., Guo Y., Sasaki M., Tabata C., Yamamoto T., Ikeda K., Amizuka N. Histological examination on osteoblastic activities in the alveolar bone of transgenic mice with induced ablation of osteocytes. Histol. Histopathol., 2013, Vol. 28, no. 3, pp. 327-335.Lin G.L., Hankenson K.D. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell Biochem., 2011, Vol. 112, no. 12, pp. 3491-3501.Lin G.L., Hankenson K.D. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell Biochem., 2011, Vol. 112, no. 12, pp. 3491-3501.Liu H., Kemeny, D.M., Heng B.C., Ouyang H.W., Melendez A.J., Cao T. The immunogenicity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells. J. Immunol., 2006, Vol. 176, no. 5, pp. 2864-2871.Liu H., Kemeny, D.M., Heng B.C., Ouyang H.W., Melendez A.J., Cao T. The immunogenicity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells. J. Immunol., 2006, Vol. 176, no. 5, pp. 2864-2871.Liu W.H., Liu J.J., Wu J., Zhang L.L., Liu F., Yin L., Zhang M.M., Yu B. Novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem cells via interleukin 10 and the JAK1/STAT3 signaling pathway. PLoS ONE, 2013, Vol. 38, no. 1, e55487. doi: 10.1371/journal.pone.0055487.Liu W.H., Liu J.J., Wu J., Zhang L.L., Liu F., Yin L., Zhang M.M., Yu B. Novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem cells via interleukin 10 and the JAK1/STAT3 signaling pathway. PLoS ONE, 2013, Vol. 38, no. 1, e55487. doi: 10.1371/journal.pone.0055487.Lu W., Fu C., Song L., Yao Y., Zhang X., Chen Z., Li Y., Ma G., Shen C. Exposure to supernatants of macrophages that phagocytized dead mesenchymal stem cells improves hypoxic cardiomyocytes survival. Int. J. Cardiol., 2012, Vol. 165, no. 2, pp. 333-340.Lu W., Fu C., Song L., Yao Y., Zhang X., Chen Z., Li Y., Ma G., Shen C. Exposure to supernatants of macrophages that phagocytized dead mesenchymal stem cells improves hypoxic cardiomyocytes survival. Int. J. Cardiol., 2012, Vol. 165, no. 2, pp. 333-340.Luk F., Carreras-Planella L., Korevaar S.S. Inflammatory conditions dictate the effect of mesenchymal stem or stromal cells on b cell function. Front. Immunol., 2017, Vol. 8, 1042. doi: 10.3389/ mmu.2017.01042.Luk F., Carreras-Planella L., Korevaar S.S. Inflammatory conditions dictate the effect of mesenchymal stem or stromal cells on b cell function. Front. Immunol., 2017, Vol. 8, 1042. doi: 10.3389/ mmu.2017.01042.Mukonoweshuro B., Brown C.J., Fisher J., Ingham E. Immunogenicity of undifferentiated and differentiated allogeneic mouse mesenchymal stem cells. J. Tissue Eng., 2014, Vol. 5, no. 1, pp. 1-15.Mukonoweshuro B., Brown C.J., Fisher J., Ingham E. Immunogenicity of undifferentiated and differentiated allogeneic mouse mesenchymal stem cells. J. Tissue Eng., 2014, Vol. 5, no. 1, pp. 1-15.Neuss S., Denecke B., Gan L., Lin Q. Transcriptome analysis of MSC and MSC-derived osteoblasts on resomer® Lt706 and Pcl: impact of biomaterial substrate on osteogenic differentiation. PLoS ONE, 2011, Vol. 6, no. 9, e23195. doi: 10.1371/journal.pone.0023195.Neuss S., Denecke B., Gan L., Lin Q. Transcriptome analysis of MSC and MSC-derived osteoblasts on resomer® Lt706 and Pcl: impact of biomaterial substrate on osteogenic differentiation. PLoS ONE, 2011, Vol. 6, no. 9, e23195. doi: 10.1371/journal.pone.0023195.New S.E., Ibrahim A., Guasti L. Towards reconstruction of epithelialized cartilages from autologous adipose tissue-derived stem cells. J. Tissue Eng. Regen. Med., 2016, Vol. 11, no. 11, pp. 3078-3089.New S.E., Ibrahim A., Guasti L. Towards reconstruction of epithelialized cartilages from autologous adipose tissue-derived stem cells. J. Tissue Eng. Regen. Med., 2016, Vol. 11, no. 11, pp. 3078-3089.Niaza K., Senatov F., Anisimova N., Kiselevskiy M., Kaloshkin S. Effect of co-incubation with mesenchymal stromal cells in cultural medium on structure and mechanical properties of polylactide-based scaffolds. BioNano Science, 2017, Vol. 7, no. 4, pp. 712-717.Niaza K., Senatov F., Anisimova N., Kiselevskiy M., Kaloshkin S. Effect of co-incubation with mesenchymal stromal cells in cultural medium on structure and mechanical properties of polylactide-based scaffolds. BioNano Science, 2017, Vol. 7, no. 4, pp. 712-717.Nich C., Takakubo Y., Pajarinen J., Ainola M., Salem A., Sillat T., Rao A.J., Raska M., Tamaki Y., Takagi M., Konttinen Y.T., Goodman S.B., Gallo J. Macrophages-key cells in the response to wear debris from joint replacements. J. Biomed. Mater. Res. A, 2013, Vol. 101, no. 10, pp. 3033-3045.Nich C., Takakubo Y., Pajarinen J., Ainola M., Salem A., Sillat T., Rao A.J., Raska M., Tamaki Y., Takagi M., Konttinen Y.T., Goodman S.B., Gallo J. Macrophages-key cells in the response to wear debris from joint replacements. J. Biomed. Mater. Res. A, 2013, Vol. 101, no. 10, pp. 3033-3045.Petri R.M., Hackel A., Hahnel K., Dumitru C.A., Bruderek K., Flohe S.B., Paschen A., Lang S., Brandau S. Activated tissue-resident mesenchymal stromal cells regulate natural killer cell immune and tissue-regenerative function. Stem Cell Reports, 2017, Vol. 9, pp. 985-998.Petri R.M., Hackel A., Hahnel K., Dumitru C.A., Bruderek K., Flohe S.B., Paschen A., Lang S., Brandau S. Activated tissue-resident mesenchymal stromal cells regulate natural killer cell immune and tissue-regenerative function. Stem Cell Reports, 2017, Vol. 9, pp. 985-998.Raggatt L.J., Partridge N.C. Cellular and molecular mechanisms of bone remodeling. J. Biol. Chem., 2010, Vol. 285, no. 33, pp. 25103-25108.Raggatt L.J., Partridge N.C. Cellular and molecular mechanisms of bone remodeling. J. Biol. Chem., 2010, Vol. 285, no. 33, pp. 25103-25108.Raicevic G., Najar M., Najimi M., El Taghdouini A., van Grunsven L.A., Sokal E., Toungouz M. Influence of inflammation on the immunological profile of adult-derived human liver mesenchymal stromal cells and stellate cells. Cytotherapy, 2015, Vol. 17, no. 2, pp. 174-185.Raicevic G., Najar M., Najimi M., El Taghdouini A., van Grunsven L.A., Sokal E., Toungouz M. Influence of inflammation on the immunological profile of adult-derived human liver mesenchymal stromal cells and stellate cells. Cytotherapy, 2015, Vol. 17, no. 2, pp. 174-185.Rauner M., Sipos W., Pietschmann P. Osteoimmunology. Int. Arch. Allergy Immunol., 2007, Vol. 143, no. 1, pp. 31-48.Rauner M., Sipos W., Pietschmann P. Osteoimmunology. Int. Arch. Allergy Immunol., 2007, Vol. 143, no. 1, pp. 31-48.Roszer T. Understanding the Mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm., 2015, Vol. 2015, no. 1, pp. 1-16.Roszer T. Understanding the Mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm., 2015, Vol. 2015, no. 1, pp. 1-16.Santo V.E., Gomes M.E., Mano J.F., Reis R.L. Controlled release strategies for bone, cartilage, and osteochondral engineering – Part I: recapitulation of native tissue healing and variables for the design of delivery systems. Tissue Eng. Part B Rev., 2013, Vol. 19, no. 4, pp. 308-326.Santo V.E., Gomes M.E., Mano J.F., Reis R.L. Controlled release strategies for bone, cartilage, and osteochondral engineering – Part I: recapitulation of native tissue healing and variables for the design of delivery systems. Tissue Eng. Part B Rev., 2013, Vol. 19, no. 4, pp. 308-326.Senatov F.S., Zadorozhnyy M.Yu., Niaza K.V., Medvedev V.V., Kaloshkin S.D., Anisimova N.Yu., Kiselevskiy M.V., Yang K-C. Shape memory effect in 3D-printed scaffolds for self-fitting implants. Eur. Polymer J., 2017, Vol. 93, no. 1, pp. 222-231.Senatov F.S., Zadorozhnyy M.Yu., Niaza K.V., Medvedev V.V., Kaloshkin S.D., Anisimova N.Yu., Kiselevskiy M.V., Yang K-C. Shape memory effect in 3D-printed scaffolds for self-fitting implants. Eur. Polymer J., 2017, Vol. 93, no. 1, pp. 222-231.Soto-Gutierrez A., Wertheim J.A., Ott H.C., Gilbert T.W. Perspectives on whole-organ assembly: moving toward transplantation on demand. J. Clin. Invest., 2012, Vol. 122, no. 11, pp. 3817-3823.Soto-Gutierrez A., Wertheim J.A., Ott H.C., Gilbert T.W. Perspectives on whole-organ assembly: moving toward transplantation on demand. J. Clin. Invest., 2012, Vol. 122, no. 11, pp. 3817-3823.Sutton M.T., Fletcher D., Ghosh S.K., Weinberg A., van Heeckeren R., Kaur S., Sadeghi Z., Hijaz A., Reese J., Lazarus H.M., Lennon D.P., Caplan A.I., Bonfield T.L. Antimicrobial properties of mesenchymal stem cells: therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int., 2016, Vol. 2016, no. 1, pp. 1-12.Sutton M.T., Fletcher D., Ghosh S.K., Weinberg A., van Heeckeren R., Kaur S., Sadeghi Z., Hijaz A., Reese J., Lazarus H.M., Lennon D.P., Caplan A.I., Bonfield T.L. Antimicrobial properties of mesenchymal stem cells: therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int., 2016, Vol. 2016, no. 1, pp. 1-12.Wang M.L., Nesti L.J., Tuli R., Lazatin J., Danielson K.G., Sharkey P.F., Tuan R.S. Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells. J. Orthop. Res., 2002, Vol. 20, no. 6, pp. 1175-1184.Wang M.L., Nesti L.J., Tuli R., Lazatin J., Danielson K.G., Sharkey P.F., Tuan R.S. Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells. J. Orthop. Res., 2002, Vol. 20, no. 6, pp. 1175-1184.Xue R., Qian Y., Li L., Yao G., Yang L., Sun Y. Polycaprolactone nanofiber scaffold enhances the osteogenic differentiation potency of various human tissue-derived mesenchymal stem cells. Stem Cell Res. Ther., 2017, Vol. 8, no. 1, p. 148.Xue R., Qian Y., Li L., Yao G., Yang L., Sun Y. Polycaprolactone nanofiber scaffold enhances the osteogenic differentiation potency of various human tissue-derived mesenchymal stem cells. Stem Cell Res. Ther., 2017, Vol. 8, no. 1, p. 148.Yagi H., Soto-Gutierrez A. Parekkadan B., Kitagawa Y, Tompkins R.G., Kobayashi N., Yarmush M.L. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant., 2010, Vol. 19, no. 6, pp. 667-679.Yagi H., Soto-Gutierrez A. Parekkadan B., Kitagawa Y, Tompkins R.G., Kobayashi N., Yarmush M.L. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant., 2010, Vol. 19, no. 6, pp. 667-679.Zhang S., Chen X., Hu Y., Wu J., Cao Q. Chen S., Gao Y. All-trans retinoic acid modulates Wnt3A-induced osteogenic differentiation of mesenchymal stem cells via activating the PI3K/AKT/GSK3beta signalling pathway. Mol. Cell. Endocrinol., 2016, Vol. 42, no. 422, pp. 243-253.Zhang S., Chen X., Hu Y., Wu J., Cao Q. Chen S., Gao Y. All-trans retinoic acid modulates Wnt3A-induced osteogenic differentiation of mesenchymal stem cells via activating the PI3K/AKT/GSK3beta signalling pathway. Mol. Cell. Endocrinol., 2016, Vol. 42, no. 422, pp. 243-253.Zhou Y., Tsai T.L., Li W.J. Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo. Ann. N. Y. Acad. Sci., 2017, Vol. 1409, no. 1, pp. 3-17.Zhou Y., Tsai T.L., Li W.J. Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo. Ann. N. Y. Acad. Sci., 2017, Vol. 1409, no. 1, pp. 3-17.Zimmermann J.A., Hettiaratchi M.H., McDevitt T.C. Enhanced Immunosuppression of T cells by sustained presentation of bioactive interferon-γ within three-dimensional mesenchymal stem cell constructs. Stem Cells Transl. Med., 2017, Vol. 6, no. 1, pp. 223-237.Zimmermann J.A., Hettiaratchi M.H., McDevitt T.C. Enhanced Immunosuppression of T cells by sustained presentation of bioactive interferon-γ within three-dimensional mesenchymal stem cell constructs. Stem Cells Transl. Med., 2017, Vol. 6, no. 1, pp. 223-237.

The authors declare that there are no conflicts of interest present.