actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problemsactabiomedica-901Research ArticleКЛИНИЧЕСКАЯ МЕДИЦИНАCLINICAL MEDICINEМ2-ПОДОБНЫЕ МАКРОФАГИ КАК ПОТЕНЦИАЛЬНЫЕ КАНДИДАТЫ В ЛЕЧЕНИИ ПОСЛЕДСТВИЙ ЦЕРЕБРАЛЬНОГО ИНСУЛЬТАM2-LIKE MACROPHAGES ARE POTENTIAL CANDIDATES FOR BRAIN STROKE OUTCOMES' TREATMENTМорозовС. А.MorozovS. A.El-gorra@rambler.ruТомашГ. В.TomashG. V.noemail@neicon.ruШевелаЕ. Я.ShevelaE. Ya.shevelak@mail.ruСахноЛ. В.SakhnoL. V.noemail@neicon.ruСмыкА. В.SmykA. V.anna-v-smyk@mail.ruСтаростинаН. М.StarostinaN. M.noemail@neicon.ruОстанинА. А.OstaninA. A.noemail@neicon.ruЧерныхЕ. Р.ChernykhE. R.bmt-novosibirsk@mail.ruНИИ клинической иммунологии СО РАМН; ГБОУ ВПО НГМУ РосздраваResearch Institute of Clinical Immunology SD RAMSГКБ № 1Research Institute of Clinical Immunology SD RAMSНИИ клинической иммунологии СО РАМНResearch Institute of Clinical Immunology SD RAMS20122805201203(2)125128Copyright © Морозов С.А., Томаш Г.В., Шевела Е.Я., Сахно Л.В., Смык А.В., Старостина Н.М., Останин А.А., Черных Е.Р., 20122012Морозов С.А., Томаш Г.В., Шевела Е.Я., Сахно Л.В., Смык А.В., Старостина Н.М., Останин А.А., Черных Е.Р.Morozov S.A., Tomash G.V., Shevela E.Y., Sakhno L.V., Smyk A.V., Starostina N.M., Ostanin A.A., Chernykh E.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/901

Целью настоящего исследования стала оценка безопасности и эффективности in vitro генерированных М2-подобных макрофагов в лечении больных с ишемическим и геморрагическим инсультом в восстановительном и резидуальном периоде. Однократное эндолюмбальное введение аутологичных макрофагов в средней дозе 17,9 х 106 клеток проведено 13 пациентам с ишемическим (n = 10) и геморрагическим (n = 3) инсультом. Через 6 месяцев после введения клеток у всех пациентов отмечалось клиническое улучшение. Отмечалось достоверное снижение балла NIHS с 8,6 ± 1,06 до 4,4 ± 0,55 (p = 0,0008), у части пациентов регрессировали нарушения чувствительности наблюдалось улучшение когнитивных функций и качество жизни. Таким образом, показана возможность генерации М2-подобных макрофагов у пациентов с инсультом, эндолюмбальное введение клеток безопасно и не вызывает выраженных побочных реакций и осложнений и, по предварительным данным, позволяет добиться улучшения двигательных и когнитивных функций.

The safety and effectiveness of in vitro generated M2-like macrophages for treatment of patients with ischemic and hemorrhagic brain stroke in reparative and residual periods has been evaluated. A single endolumbar administration of autologous M2-like macrophages in the mean dose of 17,9 х 106 cells was conducted in 13 patients with ischemic (n = 10) and hemorrhagic (n = 3) brain stroke. At 6 months after cells administration all the patients had clinical Improvement. NIHS score decreased from 8,6 ± 1,06 to 4,4 ± 0.55 (p = 0,0008), several patients showed the decrease of sensitiveness impairments, improvement of cognitive functions and enhanced quality of life. Thus, we demonstrated an ability of generation M2-like macrophages from patients with brain stroke. Endolumbar administration of these cells was safe andi didn't cause severe adverse effects and complications andi — in preliminary data — improvedi motional and cognitive functions.

инсультМ2-подобные макрофагиbrain strokeM2-like macrophagesReferencesAsher R.A., Morgenstern D.A., Moon L.D., Fawcett J.W. Chondroitin sulphate proteoglycans: inhibitory components of the glial scar // Prog Brain Res. - 2001. - Vol. 132. - P. 611-619.Asher R.A., Morgenstern D.A., Moon L.D., Fawcett J.W. Chondroitin sulphate proteoglycans: inhibitory components of the glial scar // Prog Brain Res. - 2001. - Vol. 132. - P. 611-619.Chernykh E.R., Kafanova M.Yu., Shevela E.Ya., Adonina E.I. et al. Autologous M2-like macrophage applications in children with cerebral palsy // Cell Ther. Transplant. - 2011. - Vol. 3. - P. 12-14.Chernykh E.R., Kafanova M.Yu., Shevela E.Ya., Adonina E.I. et al. Autologous M2-like macrophage applications in children with cerebral palsy // Cell Ther. Transplant. - 2011. - Vol. 3. - P. 12-14.Chernykh E.R., Shevela E.Y., Sakhno L.V., Tikhonova M.A. et al. The generation and properties of human M2-like macrophages: potential candidates for CNS repair? // Cellular Therapy and Transplantation. - 2010. - Vol. 2. - P. 20-23.Chernykh E.R., Shevela E.Y., Sakhno L.V., Tikhonova M.A. et al. The generation and properties of human M2-like macrophages: potential candidates for CNS repair? // Cellular Therapy and Transplantation. - 2010. - Vol. 2. - P. 20-23.Domeniconi M., Cao Z., Spencer T., Sivasankaran R. et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth // Neuron. - 2002. - Vol. 35. - P. 283-290.Domeniconi M., Cao Z., Spencer T., Sivasankaran R. et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth // Neuron. - 2002. - Vol. 35. - P. 283-290.Fitch M.T., Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injuryleads to increases in putative inhibitory molecules // Exp Neurol. - 1997. - Vol. 148. - P. 587-603.Fitch M.T., Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injuryleads to increases in putative inhibitory molecules // Exp Neurol. - 1997. - Vol. 148. - P. 587-603.Freire-de-Lima C.G., Xiao Y.Q., Gardai S.J., Bratton D.L. et al. Apoptotic cells, through transforming growth factor-ß, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages // J Biol Chem. - 2006. - Vol. 281. - P. 38376-38384.Freire-de-Lima C.G., Xiao Y.Q., Gardai S.J., Bratton D.L. et al. Apoptotic cells, through transforming growth factor-ß, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages // J Biol Chem. - 2006. - Vol. 281. - P. 38376-38384.Golpon H.A., Fadok V.A., Taraseviciene-Stewart L. Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth // The FASEB Journal. - 2004. - Vol. 18. -P. 1716-1718.Golpon H.A., Fadok V.A., Taraseviciene-Stewart L. Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth // The FASEB Journal. - 2004. - Vol. 18. -P. 1716-1718.Gordon S., Taylor P.R. Monocyte and macrophage heterogeneity // Nat. Rev. Immunol. - 2005. -Vol. 5. - P. 953-964.Gordon S., Taylor P.R. Monocyte and macrophage heterogeneity // Nat. Rev. Immunol. - 2005. -Vol. 5. - P. 953-964.Kigerl K.A., Gensel J.C., Ankeny D.P., Alexander J.K. et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord // J. Neurosci. - 2009. - Vol. 29. -P. 13435-13444.Kigerl K.A., Gensel J.C., Ankeny D.P., Alexander J.K. et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord // J. Neurosci. - 2009. - Vol. 29. -P. 13435-13444.Mantovani A., Sica A., Sozzani S., Allavena P. et al. The chemokine system in diverse forms of macrophage activation and polarization // Trends Immunol. - 2004. - Vol. 25. - P. 677-686.Mantovani A., Sica A., Sozzani S., Allavena P. et al. The chemokine system in diverse forms of macrophage activation and polarization // Trends Immunol. - 2004. - Vol. 25. - P. 677-686.McPhail L.T., Stirling D.P., Tetzlaff W., Kwiecien J.M. et al. The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury // Eur. J. Neurosci. - 2004. - Vol. 20. - P. 1984-1994.McPhail L.T., Stirling D.P., Tetzlaff W., Kwiecien J.M. et al. The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury // Eur. J. Neurosci. - 2004. - Vol. 20. - P. 1984-1994.Mosser D.M. The many faces of macrophage activation // J. Leukocyte Biol. - 2003. - Vol. 73. -P. 209-212.Mosser D.M. The many faces of macrophage activation // J. Leukocyte Biol. - 2003. - Vol. 73. -P. 209-212.Shechter R., London A., Varol C., Raposo C. et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice // PLoS Medicine. -2009. - Vol. 6. - P. 1-16.Shechter R., London A., Varol C., Raposo C. et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice // PLoS Medicine. -2009. - Vol. 6. - P. 1-16.Ziv Y., Avidan H., Pluchino S., Martino G. et al. Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury // Proc. Natl. Acad. Sci. USA. -2006. - Vol. 103. - P. 13174-13179.Ziv Y., Avidan H., Pluchino S., Martino G. et al. Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury // Proc. Natl. Acad. Sci. USA. -2006. - Vol. 103. - P. 13174-13179.

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