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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Annals of Clinical and Experimental Neurology</journal-id><journal-title-group><journal-title xml:lang="en">Annals of Clinical and Experimental Neurology</journal-title><trans-title-group xml:lang="ru"><trans-title>Анналы клинической и экспериментальной неврологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2075-5473</issn><issn publication-format="electronic">2409-2533</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">557</article-id><article-id pub-id-type="doi">10.25692/ACEN.2018.5.2</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Neurotransplantation: the time has come?</article-title><trans-title-group xml:lang="ru"><trans-title>Нейротрансплантация: настало ли время?</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Illarioshkin</surname><given-names>Sergey N.</given-names></name><name xml:lang="ru"><surname>Иллариошкин</surname><given-names>Сергей Николаевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>snillario@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Research Center of Neurology</institution></aff><aff><institution xml:lang="ru">ФГБНУ «Научный центр неврологии»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2018-12-26" publication-format="electronic"><day>26</day><month>12</month><year>2018</year></pub-date><volume>12</volume><issue>5S</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>16</fpage><lpage>24</lpage><history><date date-type="received" iso-8601-date="2018-12-26"><day>26</day><month>12</month><year>2018</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2018, Illarioshkin S.N.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2018, Illarioshkin S.N.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="en">Illarioshkin S.N.</copyright-holder><copyright-holder xml:lang="ru">Illarioshkin S.N.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://annaly-nevrologii.com/pathID/article/view/557">https://annaly-nevrologii.com/pathID/article/view/557</self-uri><abstract xml:lang="en"><p>Problems in curing disorders of the brain are caused by several characteristic features of the nervous tissue, such as postmitotic nature of neurons, their limited reparative potential, significant energy dependence, etc. Because of special vulnerability and extremely high specialization, neurons are very sensitive to the action of any pathological factors, while existing possibilities of their trophic and metabolic support are scanty. Therefore, the creation of new reparative strategies, including substitutive cell technologies, is immediate task in neurology. Neurodegenerative disorders, Parkinson’s disease (PD), Huntington’s disease and others, are an “ideal” model for elaborating such strategies. As main motor symptoms of PD are related to degeneration of the dopaminergic nigrostriatal pathway, treatment of these patients, theoretically, may be based on transplantation of dopamine-producing neurons into the striatum. In the paper, analyzed are the results of many-year experimental (on models of parkinsonism) and preliminary clinical trials of neurotransplantation with the use of fetal tissues (dopaminergic cells of the ventral midbrain) and dopaminergic neurons differentiated from embryonal stem cells and induced pluripotent. Newest scientific achievements in this field, improvement of cell protocols and successful resolving of a number of technical and medical problems allow saying that neurotransplantation becomes clinical reality just before our eyes.</p></abstract><trans-abstract xml:lang="ru"><p>Сложности лечения заболеваний мозга обусловлены рядом характерных особенностей нервной ткани, таких как постмитотическая природа нейронов, их ограниченный репаративный потенциал, значительная энергозависимость и т.д. В связи с особой ранимостью и высочайшей специализацией нейроны очень чувствительны к действию любых патологических факторов, а существующие возможности их трофической и метаболической поддержки весьма ограничены. Поэтому в неврологии неотложной является разработка новых репаративных стратегий, в том числе заместительных клеточных технологий. ≪Идеальной≫ моделью для разработки таких стратегий являются нейродегенеративные заболевания – болезнь Паркинсона (БП), болезнь</p> <p>Гентингтона и др. В связи с тем, что основные двигательные симптомы БП связаны с дегенерацией дофаминергического нигростриатного пути, лечение таких пациентов, теоретически, может базироваться на трансплантации дофамин-продуцирующих нейронов в область полосатого тела.</p> <p>В статье анализируются результаты многолетних экспериментальных (на моделях паркинсонизма) и предварительных клинических исследований нейротрансплантации с использованием фетальных тканей (дофаминергические клетки вентральной области среднего мозга), а также дофаминергических нейронов, дифференцированных из эмбриональных стволовых клеток и индуцируемых плюрипотентных стволовых клеток. Новейшие достижения науки в этой области, усовершенствование клеточных протоколов и успешное решение ряда технических и медицинских проблем позволяют говорить о том, что нейротрансплантация на наших глазах становится клинической реальностью.</p></trans-abstract><kwd-group xml:lang="en"><kwd>neurotransplantation</kwd><kwd>dopaminergic neurons</kwd><kwd>fetal cells</kwd><kwd>induced pluripotent stem cells</kwd><kwd>Parkinson’s disease</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>нейротрансплантация</kwd><kwd>дофаминергические нейроны</kwd><kwd>фетальные клетки</kwd><kwd>индуцированные плюрипотентные стволовые клетки</kwd><kwd>болезнь Паркинсона</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Viktorov I.V., Savchenko E.A., Ukhova O.V. et al. [Multipotent stem cells and progenitor cells of the olfactory epithelium]. Kletochnyye tekhnologii v biologii i meditsine 2006; 4: 185–193. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Викторов И.В., Савченко Е.А., Ухова О.В. и др. Мультипотентные стволовые и прогениторные клетки обонятельного эпителия. Клеточные технологии в биологии и медицине 2006; 4: 185–193.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">Illarioshkin S.N., Khaspekov L.G., Grivennikov I.A. Modelirovaniye bolezni Parkinsona s ispol’zovaniyem indutsirovannykh plyuripotentnykh stvolovykh kletok. [Modeling of Parkinson’s disease with the use of induced pluripotent stem cells] Moscow: Sovero-press, 2016. 183 p. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Иллариошкин С.Н., Хаспеков Л.Г., Гривенников И.А. Моделирование болезни Паркинсона и использованием индуцированных плюрипотентных стволовых клеток. М.: Соверо-пресс, 2016. 183 c.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">Lebedeva O.S., Lagar’kova M.A., Kiselev S.L. et al. [Morphofunctional properties of induced pluripotent stem cells derived from human skin fibroblasts and differentiated into dopaminergic neurons]. Neyrokhimiya 2013; 3: 233–241.(In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Лебедева О.С., Лагарькова М.А., Киселев С.Л. и др. Морфофункциональные свойства индуцированных плюрипотентных стволовых клеток, полученных из фибробластов кожи человека и дифференцированных в дофаминергические нейроны. Нейрохимия 2013; 3: 233–241.</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">Stavrovskaya A.V., Voronkov D.N., Yamshchikova N.G. et al. [Morphochemical evaluation of the results of neurotransplantation in experimental parkinsonism]. Annals of Clinical and Experimental Neurology 2015; 2: 28–32. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Ставровская А.В., Воронков Д.Н., Ямщикова Н.Г. и др. Морфохимическая оценка результатов нейротрансплантации при экспериментальном паркинсонизме. Анналы клинической и экспериментальной неврологии 2015; 2: 28–32.</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">Stavrovskaya A.V., Yamshchikova N.G., Ol’shansky А.S. et al. [Transplantation of neuronal precursors obtained from induced pluripotent stem cells in the striatum of rats with a toxic model of Huntington’s disease]. Annals of Clinical and Experimental Neurology 2016; 4: 39–44. (in Russ.)</mixed-citation><mixed-citation xml:lang="ru">Ставровская А.В., Ямщикова Н.Г., Ольшанский А.С. и др. Трансплантация нейрональных предшественников, полученных из индуцированных плюрипотентных стволовых клеток, в стриатум крыс с токсической моделью болезни Гентингтона. Анналы клинической и экспериментальной неврологии 2016; 4: 39–44.</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">Khaspekov L.G., Stavrovskaya A.V., Khudoyerkov R.M. et al. [Experimental aspects of the study of dopaminergic neurons obtained from human skin fibroblasts with the technology of induced pluripotent stem cells]. In: [S.N. Illarioshkin, O.S. Levin (Eds.) Parkinson’s Disease and Movement Disorders]. Moscow:Sovero-press, 2014: 49–55. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Хаспеков Л.Г., Ставровская А.В., Худоерков Р.М. и др. Экспериментальные аспекты изучения дофаминергических нейронов, полученных из фибробластов кожи человека на основе технологии индуцированных плюрипотентных стволовых клеток. В сб.: Болезнь Паркинсона и расстройства движений (под ред. С.Н. Иллариошкина, О.С. Левина). М.: Соверо-пресс, 2014: 49–55.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">Shtok V.N., Ugryumov M.V., Fedorova N.V. et al. [Neurotransplantation in the treatment of Parkinson’s disease (follow-up study)]. Zhurnal voprosy neyrokhirurgii im. N.N.Burdenko 2002; 2: 29–33. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Шток В.Н., Угрюмов М.В., Федорова Н.В. и др. Нейротрансплантация в лечении болезни Паркинсона (катамнез). Журнал Вопросы нейрохирургии им. Н.Н.Бурденко 2002; 2: 29–33.</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><mixed-citation>Avaliani N., Sørensen A.T., Ledri M. et al. Optogenetics reveal delayed afferent synaptogenesis on grafted human-induced pluripotent stem cell-derived neural progenitors. Stem Cells 2014; 32: 3088–3098. DOI: 10.1002/stem.1823. PMID: 25183299.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Bakay R.A., Fiandaca M.S., Barrow D.L. et al. Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced Parkinson-like syndrome in primates. Appl Neurophysiol 1985; 48: 358–361. PMID: 3879797.</mixed-citation></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">Barker R.A., Parmar M., Kirkeby A. et al. Are stem cell-based therapies for Parkinson’s disease ready for the clinic in 2016? J Parkinsons Dis 2016; 6: 57–63.</mixed-citation><mixed-citation xml:lang="ru">Barker R.A., Parmar M., Kirkeby A. et al. Are stem cell-based therapies for Parkinson’s disease ready for the clinic in 2016? J Parkinsons Dis 2016; 6: 57–63. DOI: 10.3233/JPD-160798. PMID: 27003785.</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">DOI: 10.3233/JPD-160798. PMID: 27003785.</mixed-citation><mixed-citation xml:lang="ru">Bjorklund A., Kordower J.H. Cell therapy for Parkinson’s disease: what next?Mov Disord 2013; 28: 110–115. DOI: 10.1002/mds.25343. PMID: 23390097.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">Bjorklund A., Kordower J.H. Cell therapy for Parkinson’s disease: what next? Mov Disord 2013; 28: 110–115. DOI: 10.1002/mds.25343. PMID: 23390097.</mixed-citation><mixed-citation xml:lang="ru">Bjorklund A., Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 1979; 177: 555–560. PMID:574053.</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">Bjorklund A., Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 1979; 177: 555–560. PMID:</mixed-citation><mixed-citation xml:lang="ru">Brundin P., Kordower J.H. Neuropathology in transplants in Parkinson’s disease: implications for disease pathogenesis and the future of cell therapy. Prog Brain Res 2012; 200: 221–241. DOI: 10.1016/B978-0-444-59575-1.00010-7.PMID: 23195421.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">574053.</mixed-citation><mixed-citation xml:lang="ru">Brundin P., Strecker R.E., Lindvall O. et al. Intracerebral grafting of dopamine neurons. Experimental basis for clinical trials in patients with Parkinson’s disease. Ann NY Acad Sci 1987; 495: 473–496. PMID: 3474955.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">Brundin P., Kordower J.H. Neuropathology in transplants in Parkinson’s disease:</mixed-citation><mixed-citation xml:lang="ru">Brundin P., Strecker R.E., Widner H. et al. Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp Brain Res 1988;70: 192–208. PMID: 3402564.</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">implications for disease pathogenesis and the future of cell therapy. Prog Brain Res 2012; 200: 221–241. DOI: 10.1016/B978-0-444-59575-1.00010-7. PMID: 23195421.</mixed-citation><mixed-citation xml:lang="ru">Cai J., Yang M., Poremsky E. et al. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats. Stem Cells Dev 2010;19: 1017–1023. DOI: 10.1089/scd.2009.0319. PMID:19824823.</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">Brundin P., Strecker R.E., Lindvall O. et al. Intracerebral grafting of dopamine neurons. Experimental basis for clinical trials in patients with Parkinson’s disease. Ann NY Acad Sci 1987; 495: 473–496. PMID: 3474955.</mixed-citation><mixed-citation xml:lang="ru">Caiazzo M., Dell’Anno M.T., Dvoretskova E. et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 2011;476: 224–227. DOI: 10.1038/nature10284. PMID: 2172532.</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">Brundin P., Strecker R.E., Widner H. et al. Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp Brain Res 1988; 70: 192–208. PMID: 3402564.</mixed-citation><mixed-citation xml:lang="ru">Carta M., Carlsson T., Munoz A. et al. Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson’s disease. Mov Disord 2010; 25: S174 S179. DOI: 10.1002/mds.22792. PMID: 20187238.</mixed-citation></citation-alternatives></ref><ref id="B19"><label>19.</label><citation-alternatives><mixed-citation xml:lang="en">Cai J., Yang M., Poremsky E. et al. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats. Stem Cells Dev 2010; 19: 1017–1023. DOI: 10.1089/scd.2009.0319. PMID:19824823.</mixed-citation><mixed-citation xml:lang="ru">Chang Y.L., Chen S.J., Kao C.L. et al. Docosahexaenoic acid promotes dopaminergic differentiation in induced pluripotent stem cells and inhibits teratoma formation in rats with Parkinson-like pathology. Cell Transplant 2012; 21: 313–332. DOI:10.3727/096368911X580572. PMID: 21669041.</mixed-citation></citation-alternatives></ref><ref id="B20"><label>20.</label><citation-alternatives><mixed-citation xml:lang="en">Caiazzo M., Dell’Anno M.T., Dvoretskova E. et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 2011; 476: 224–227. DOI: 10.1038/nature10284. PMID: 2172532.</mixed-citation><mixed-citation xml:lang="ru">Clarke D.J., Brundin P., Strecker R.E. et al. Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry. Exp Brain Res 1988; 73: 115–126. PMID: 3145209.</mixed-citation></citation-alternatives></ref><ref id="B21"><label>21.</label><citation-alternatives><mixed-citation xml:lang="en">Carta M., Carlsson T., Munoz A. et al. Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson’s disease. Mov Disord 2010; 25: S174–S179. DOI: 10.1002/mds.22792. PMID: 20187238.</mixed-citation><mixed-citation xml:lang="ru">Dell’Anno M.T., Caiazzo M., Leo D. et al. Remote control of induced dopaminergic neurons in parkinsonian rats. J Clin Invest 2014; 124: 3215–3229. DOI:10.1172/JCI74664. PMID: 24937431.</mixed-citation></citation-alternatives></ref><ref id="B22"><label>22.</label><citation-alternatives><mixed-citation xml:lang="en">Chang Y.L., Chen S.J., Kao C.L. et al. Docosahexaenoic acid promotes dopaminergic differentiation in induced pluripotent stem cells and inhibits teratoma formation in rats with Parkinson-like pathology. Cell Transplant 2012; 21:313–332. DOI: 10.3727/096368911X580572. PMID: 21669041.</mixed-citation><mixed-citation xml:lang="ru">Demuth H.-U., Dijkhuizen R.M., Farr T.D. et al. Recent progress in translational research on neurovascular and neurodegenerative disorders. Restor Neurol Neurosci 2017; 35: 87–103. DOI: 10.3233/RNN-160690. PMID: 28059802.</mixed-citation></citation-alternatives></ref><ref id="B23"><label>23.</label><citation-alternatives><mixed-citation xml:lang="en">Clarke D.J., Brundin P., Strecker R.E. et al. Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry. Exp Brain Res 1988; 73: 115–126. PMID: 3145209.</mixed-citation><mixed-citation xml:lang="ru">Doi D., Samata B., Katsukawa M. et al. Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation. Stem Cell Reports 2014; 2: 337–350. DOI: 10.1016/j.stemcr.2014.01.013. PMID: 24672756.</mixed-citation></citation-alternatives></ref><ref id="B24"><label>24.</label><citation-alternatives><mixed-citation xml:lang="en">Dell’Anno M.T., Caiazzo M., Leo D. et al. Remote control of induced dopaminergic neurons in parkinsonian rats. J Clin Invest 2014; 124: 3215–3229. DOI: 10.1172/JCI74664. PMID: 24937431.</mixed-citation><mixed-citation xml:lang="ru">Freed C.R., Greene P.E., Breeze R.E. et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001; 344: 710–719. DOI: 10.1056/NEJM200103083441002. PMID: 11236774.</mixed-citation></citation-alternatives></ref><ref id="B25"><label>25.</label><citation-alternatives><mixed-citation xml:lang="en">Demuth H.-U., Dijkhuizen R.M., Farr T.D. et al. Recent progress in translational research on neurovascular and neurodegenerative disorders. Restor Neurol Neurosci 2017; 35: 87–103. DOI: 10.3233/RNN-160690. PMID: 28059802.</mixed-citation><mixed-citation xml:lang="ru">Fundamental neuroscience (eds. L. Squire, D. Berg, Bloom F. et al.). 3d ed. Academic Press, 2008.</mixed-citation></citation-alternatives></ref><ref id="B26"><label>26.</label><citation-alternatives><mixed-citation xml:lang="en">Doi D., Samata B., Katsukawa M. et al. Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation. Stem Cell Reports 2014; 2: 337–350. DOI: 10.1016/j.stemcr.2014.01.013. PMID: 24672756.</mixed-citation><mixed-citation xml:lang="ru">Goetz C.G., Stebbins G.T., Klawans H.L. et al. United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up. Neurology 1991; 41: 1719–1722. PMID: 1944898.</mixed-citation></citation-alternatives></ref><ref id="B27"><label>27.</label><citation-alternatives><mixed-citation xml:lang="en">Freed C.R., Greene P.E., Breeze R.E. et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001; 344: 710–719. DOI: 10.1056/NEJM200103083441002. PMID: 11236774.</mixed-citation><mixed-citation xml:lang="ru">Gross R.E., Watts R.L., Hauser R.A. et al. Intrastriatal transplantation of microcarrier-bound human retinal pigment epithelial cells versus sham surgery in patients with advanced Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 2011; 10: 509–519. DOI: 10.1016/S1474-4422(11)70097-7. PMID: 21565557.</mixed-citation></citation-alternatives></ref><ref id="B28"><label>28.</label><citation-alternatives><mixed-citation xml:lang="en">Fundamental neuroscience (eds. L. Squire, D. Berg, Bloom F. et al.). 3d ed. Academic Press, 2008.</mixed-citation><mixed-citation xml:lang="ru">Hagell P., Piccini P., Bjorklund A. et al. Dyskinesias following neural transplantation in Parkinson’s disease. Nature Neurosci 2002; 5: 627–628. DOI:10.1038/nn863. PMID: 12042822.</mixed-citation></citation-alternatives></ref><ref id="B29"><label>29.</label><citation-alternatives><mixed-citation xml:lang="en">Goetz C.G., Stebbins G.T., Klawans H.L. et al. United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up. Neurology 1991; 41: 1719–1722. PMID: 1944898.</mixed-citation><mixed-citation xml:lang="ru">Hallett P.J., Deleidi M., Astradsson A. et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson’s disease. Cell Stem Cell 2015; 16: 269–274. DOI:10.1016/j.stem.2015.01.018. PMID: 25732245.</mixed-citation></citation-alternatives></ref><ref id="B30"><label>30.</label><citation-alternatives><mixed-citation xml:lang="en">Gross R.E., Watts R.L., Hauser R.A. et al. Intrastriatal transplantation of microcarrier-bound human retinal pigment epithelial cells versus sham surgery in patients with advanced Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 2011; 10: 509–519. DOI: 10.1016/S1474-4422(11)70097-7. PMID: 21565557.</mixed-citation><mixed-citation xml:lang="ru">Hargus G., Cooper O., Deleidi M. et al. Differentiated Parkinson patient-derived induced pluripotent cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci USA 2010; 107: 15921–15926. DOI: 10.1073/pnas.1010209107. PMID: 20798034.</mixed-citation></citation-alternatives></ref><ref id="B31"><label>31.</label><citation-alternatives><mixed-citation xml:lang="en">Hagell P., Piccini P., Bjorklund A. et al. Dyskinesias following neural transplantation in Parkinson’s disease. Nature Neurosci 2002; 5: 627–628. DOI: 10.1038/nn863. PMID: 12042822.</mixed-citation><mixed-citation xml:lang="ru">Kauhausen J.A., Thompson L.H., Parish C.L. Chondroitinase improves midbrain pathway reconstruction by transplanted dopamine progenitors in Parkinsonian mice. Mol Cell Neurosci 2015; 69: 22–29. DOI: 10.1016/j.mcn.2015.10.002. PMID: 26463051.</mixed-citation></citation-alternatives></ref><ref id="B32"><label>32.</label><citation-alternatives><mixed-citation xml:lang="en">Hallett P.J., Deleidi M., Astradsson A. et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson’s disease. Cell Stem Cell 2015; 16: 269–274. DOI: 10.1016/j.stem.2015.01.018. PMID: 25732245.</mixed-citation><mixed-citation xml:lang="ru">Kefalopoulou Z., Politis M., Piccini P. et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol 2014; 71: 83–87. DOI:10.1001/jamaneurol.2013.4749. PMID: 24217017.</mixed-citation></citation-alternatives></ref><ref id="B33"><label>33.</label><citation-alternatives><mixed-citation xml:lang="en">Hargus G., Cooper O., Deleidi M. et al. Differentiated Parkinson patient-derived induced pluripotent cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci USA 2010; 107: 15921–15926. DOI: 10.1073/pnas.1010209107. PMID: 20798034.</mixed-citation><mixed-citation xml:lang="ru">Kikuchi T., Morizane A., Doi D. et al. Survival of human induced pluripotent stem cell derived midbrain dopaminergic neurons in the brain of a primate model of Parkinson’s disease. J Parkinsons Dis 2011; 1: 395–412. DOI: 10.3233/ JPD-2011-11070. PMID: 23933658.</mixed-citation></citation-alternatives></ref><ref id="B34"><label>34.</label><citation-alternatives><mixed-citation xml:lang="en">Kauhausen J.A., Thompson L.H., Parish C.L. Chondroitinase improves midbrain pathway reconstruction by transplanted dopamine progenitors in Parkinsonian mice. Mol Cell Neurosci 2015; 69: 22–29. DOI: 10.1016/j.mcn.2015.10.002. PMID: 26463051.</mixed-citation><mixed-citation xml:lang="ru">Kikuchi T., Morizane A., Doi D. et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 2017; 548:592–596. DOI:10.1038/nature23664. PMID: 28858313.</mixed-citation></citation-alternatives></ref><ref id="B35"><label>35.</label><citation-alternatives><mixed-citation xml:lang="en">Kefalopoulou Z., Politis M., Piccini P. et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol 2014; 71: 83–87. DOI: 10.1001/jamaneurol.2013.4749. PMID: 24217017.</mixed-citation><mixed-citation xml:lang="ru">Kim D., Kim C.H., Moon J.I. et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 2009;4: 472–476. DOI: 10.1016/j.stem.2009.05.005. PMID: 19481515.</mixed-citation></citation-alternatives></ref><ref id="B36"><label>36.</label><citation-alternatives><mixed-citation xml:lang="en">Kikuchi T., Morizane A., Doi D. et al. Survival of human induced pluripotent stem cell-derived midbrain dopaminergic neurons in the brain of a primate model of Parkinson’s disease. J Parkinsons Dis 2011; 1: 395–412. DOI: 10.3233/JPD-2011-11070. PMID: 23933658.</mixed-citation><mixed-citation xml:lang="ru">Kimmelman J., Heslop H.E., Sugarman J. et al. New ISSCR guidelines: clinical translation of stem cell research. Lancet 2016; 387: 1979–1981. DOI:10.1016/S0140-6736(16)30390-7. PMID: 27179752.</mixed-citation></citation-alternatives></ref><ref id="B37"><label>37.</label><citation-alternatives><mixed-citation xml:lang="en">Kikuchi T., Morizane A., Doi D. et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 2017; 548: 592–596. DOI: 10.1038/nature23664. PMID: 28858313.</mixed-citation><mixed-citation xml:lang="ru">Lane E.L., Vercammen L., Cenci M.A., Brundin P. Priming for L-DOPA-induced abnormal involuntary movements increases the severity of amphetamine-induced dyskinesia in grafted rats. Exp Neurol 2009; 219: 355–358. DOI: 10.1016/j.expneurol.2009.04.010. PMID: 19393238.</mixed-citation></citation-alternatives></ref><ref id="B38"><label>38.</label><citation-alternatives><mixed-citation xml:lang="en">Kim D., Kim C.H., Moon J.I. et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 2009;4: 472–476. DOI: 10.1016/j.stem.2009.05.005. PMID: 19481515.</mixed-citation><mixed-citation xml:lang="ru">Lindvall O. Treatment of Parkinson’s disease using cell transplantation. Philos Trans R Soc Lond B Biol Sci 2015; 370: 20140370. DOI: 10.1098/rstb.2014.0370. PMID: 26416681.</mixed-citation></citation-alternatives></ref><ref id="B39"><label>39.</label><citation-alternatives><mixed-citation xml:lang="en">Kimmelman J., Heslop H.E., Sugarman J. et al. New ISSCR guidelines: clinical translation of stem cell research. Lancet 2016; 387: 1979–1981. DOI: 10.1016/S0140-6736(16)30390-7. PMID: 27179752.</mixed-citation><mixed-citation xml:lang="ru">Lindvall O. Clinical translation of stem cell transplantation in Parkinson’s disease. J Intern Med 2016; 279: 30–40. DOI: 10.1111/joim.12415. PMID:26332959.</mixed-citation></citation-alternatives></ref><ref id="B40"><label>40.</label><citation-alternatives><mixed-citation xml:lang="en">Lane E.L., Vercammen L., Cenci M.A., Brundin P. Priming for L-DOPA- induced abnormal involuntary movements increases the severity of amphetamine-induced dyskinesia in grafted rats. Exp Neurol 2009; 219: 355–358. DOI:10.1016/j.expneurol.2009.04.010. PMID: 19393238.</mixed-citation><mixed-citation xml:lang="ru">Lindvall O., Sawle G., Widner H. et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol 1994; 35: 172–180. DOI: 10.1002/ana.410350208. PMID: 8109898.</mixed-citation></citation-alternatives></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">Lindvall O. Treatment of Parkinson’s disease using cell transplantation. Philos Trans R Soc Lond B Biol Sci 2015; 370: 20140370. DOI: 10.1098/rstb.2014.0370.PMID: 26416681.</mixed-citation><mixed-citation xml:lang="ru">Mínguez-Castellanos A., Escamilla-Sevilla F., Hotton G.R. et al. Carotid body autotransplantation in Parkinson disease: a clinical anSSCRd positron emission tomography study. J Neurol Neurosurg Psychiatry 2007; 78: 825–831. DOI: 10.1136/jnnp.2006.106021. PMID: 17220289.</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><citation-alternatives><mixed-citation xml:lang="en">Lindvall O. Clinical translation of stem cell transplantation in Parkinson’s disease. J Intern Med 2016; 279: 30–40. DOI: 10.1111/joim.12415. PMID:26332959.</mixed-citation><mixed-citation xml:lang="ru">Morizane A., Doi D., Kikuchi T. et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Reports 2013; 1: 283–292. DOI: 10.1016/j.stemcr. 2013.08.007. PMID: 24319664.</mixed-citation></citation-alternatives></ref><ref id="B43"><label>43.</label><citation-alternatives><mixed-citation xml:lang="en">Lindvall O., Sawle G., Widner H. et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol 1994; 35: 172–180. DOI: 10.1002/ana.410350208. PMID: 8109898.</mixed-citation><mixed-citation xml:lang="ru">Neal E.G., Liska M.G., Lippert T. et al. An update on intracerebral stem cell grafts. Expert Rev Neurother 2018; 18: 557–572. DOI:10.1080/14737175.2018.1491309. PMID: 29961357.</mixed-citation></citation-alternatives></ref><ref id="B44"><label>44.</label><citation-alternatives><mixed-citation xml:lang="en">Mínguez-Castellanos A., Escamilla-Sevilla F., Hotton G.R. et al. Carotid body autotransplantation in Parkinson disease: a clinical anSSCRd positron emission tomography study. J Neurol Neurosurg Psychiatry 2007; 78: 825–831. DOI: 10.1136/jnnp.2006.106021. PMID: 17220289.</mixed-citation><mixed-citation xml:lang="ru">Nishimura K., Murayama S., Takahashi J. Identification of neurexophilin 3 as a novel supportive factor for survival of induced pluripotent stem cell-derived dopaminergic progenitors. Stem Cells Transl Med 2015; 4: 932–944. DOI:10.5966/sctm.2014-0197. PMID: 26041738.</mixed-citation></citation-alternatives></ref><ref id="B45"><label>45.</label><citation-alternatives><mixed-citation xml:lang="en">Morizane A., Doi D., Kikuchi T. et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Reports 2013; 1: 283–292. DOI: 10.1016/j.stemcr. 2013.08.007. PMID: 24319664.</mixed-citation><mixed-citation xml:lang="ru">Okita K., Matsumura Y., Sato Y. et al. A more efficient method to generate integration-free human iPS cells. Nat Methods 2011; 8: 409–412. DOI: 10.1038/nmeth.1591. PMID: 21460823.</mixed-citation></citation-alternatives></ref><ref id="B46"><label>46.</label><citation-alternatives><mixed-citation xml:lang="en">Neal E.G., Liska M.G., Lippert T. et al. An update on intracerebral stem cell grafts. Expert Rev Neurother 2018; 18: 557–572. DOI: 10.1080/14737175.2018.1491309. PMID: 29961357.</mixed-citation><mixed-citation xml:lang="ru">Olanow C.W., Goetz C.G., Kordower J.H. et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 2003; 54: 403–414. DOI: 10.1002/ana.10720. PMID: 12953276.</mixed-citation></citation-alternatives></ref><ref id="B47"><label>47.</label><citation-alternatives><mixed-citation xml:lang="en">Nishimura K., Murayama S., Takahashi J. Identification of neurexophilin 3 as a novel supportive factor for survival of induced pluripotent stem cell-derived dopaminergic progenitors. Stem Cells Transl Med 2015; 4: 932–944. DOI: 10.5966/sctm.2014-0197. PMID: 26041738.</mixed-citation><mixed-citation xml:lang="ru">Olanow C.W., Isacson O. Stem cells for Parkinson’s disease: advancing science but protecting patients. Mov Disord 2012; 27: 1475–1477. DOI: 10.1002/mds.25170. PMID: 23032987.</mixed-citation></citation-alternatives></ref><ref id="B48"><label>48.</label><citation-alternatives><mixed-citation xml:lang="en">Okita K., Matsumura Y., Sato Y. et al. A more efficient method to generate integration-free human iPS cells. Nat Methods 2011; 8: 409–412. DOI: 10.1038/nmeth.1591. PMID: 21460823.</mixed-citation><mixed-citation xml:lang="ru">Olanow C.W., Schapira A.H. Therapeutic prospects for Parkinson disease. Ann Neurol 2013; 74: 337–347. DOI: 10.1002/ana.24011. PMID: 2403834.</mixed-citation></citation-alternatives></ref><ref id="B49"><label>49.</label><citation-alternatives><mixed-citation xml:lang="en">Olanow C.W., Goetz C.G., Kordower J.H. et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 2003; 54: 403–414. DOI: 10.1002/ana.10720. PMID: 12953276.</mixed-citation><mixed-citation xml:lang="ru">Park Y.S., Lee J.W., Kwon H.B., Kwak K.A. Current perspectives regarding stem cell-based therapy for ischemic stroke. Curr Pharm Des 2018. DOI: 10.2174/1381612824666180604111806. PMID: 29866000 [Epub ahead of print].</mixed-citation></citation-alternatives></ref><ref id="B50"><label>50.</label><citation-alternatives><mixed-citation xml:lang="en">Olanow C.W., Isacson O. Stem cells for Parkinson’s disease: advancing science but protecting patients. Mov Disord 2012; 27: 1475–1477. DOI: 10.1002/mds.25170. PMID: 23032987.</mixed-citation><mixed-citation xml:lang="ru">Petit G.H., Olsson T.T., Brundin P. The future of cell therapies and brain repair: Parkinson’s disease leads the way. Neuropathol Appl Neurobiol 2014; 40:60–70. DOI: 10.1111/nan.12110. PMID: 24372386.</mixed-citation></citation-alternatives></ref><ref id="B51"><label>51.</label><citation-alternatives><mixed-citation xml:lang="en">Olanow C.W., Schapira A.H. Therapeutic prospects for Parkinson disease. Ann Neurol 2013; 74: 337–347. DOI: 10.1002/ana.24011. PMID: 2403834.</mixed-citation><mixed-citation xml:lang="ru">Poewe W., Seppi K., Tanner C.M. et al. Parkinson’s disease. Nat Rev Dis Primers 2017; 3: 17013. DOI: 10.1038/nrdp.2017.13. PMID: 28332488.</mixed-citation></citation-alternatives></ref><ref id="B52"><label>52.</label><citation-alternatives><mixed-citation xml:lang="en">Park Y.S., Lee J.W., Kwon H.B., Kwak K.A. Current perspectives regarding stem cell-based therapy for ischemic stroke. Curr Pharm Des 2018. DOI: 10.2174/1381612824666180604111806. PMID: 29866000 [Epub ahead of print].</mixed-citation><mixed-citation xml:lang="ru">Rhee Y.H., Ko J.Y., Chang M.Y. et al. Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest 2011; 121: 2326–2335. DOI: 10.1172/JCI45794. PMID: 21576821.</mixed-citation></citation-alternatives></ref><ref id="B53"><label>53.</label><citation-alternatives><mixed-citation xml:lang="en">Petit G.H., Olsson T.T., Brundin P. The future of cell therapies and brainrepair: Parkinson’s disease leads the way. Neuropathol Appl Neurobiol 2014; 40: 60–70. DOI: 10.1111/nan.12110. PMID: 24372386.</mixed-citation><mixed-citation xml:lang="ru">Spencer D.D., Robbins R.J., Naftolin F. et al. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med 1992; 327: 1541–1548. DOI: 10.1056/NEJM199211263272201. PMID: 1435880.</mixed-citation></citation-alternatives></ref><ref id="B54"><label>54.</label><citation-alternatives><mixed-citation xml:lang="en">Poewe W., Seppi K., Tanner C.M. et al. Parkinson’s disease. Nat Rev Dis Primers 2017; 3: 17013. DOI: 10.1038/nrdp.2017.13. PMID: 28332488.</mixed-citation><mixed-citation xml:lang="ru">Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663–676. DOI: 10.1016/j.cell.2006.07.024. PMID: 16904174.</mixed-citation></citation-alternatives></ref><ref id="B55"><label>55.</label><citation-alternatives><mixed-citation xml:lang="en">Rhee Y.H., Ko J.Y., Chang M.Y. et al. Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest 2011; 121: 2326–2335. DOI: 10.1172/JCI45794. PMID: 21576821.</mixed-citation><mixed-citation xml:lang="ru">Wernig M., Zhao J.P., Pruszak J. et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 2008; 105: 5856–5861. DOI: 10.1073/pnas.0801677105. PMID: 18391196.</mixed-citation></citation-alternatives></ref><ref id="B56"><label>56.</label><mixed-citation>Spencer D.D., Robbins R.J., Naftolin F. et al. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med 1992; 327: 1541–1548. DOI: 10.1056/NEJM199211263272201. PMID: 1435880.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663–676. DOI: 10.1016/j.cell.2006.07.024. PMID: 16904174.</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Wernig M., Zhao J.P., Pruszak J. et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 2008; 105: 5856–5861.DOI: 10.1073/pnas.0801677105. PMID: 18391196.</mixed-citation></ref></ref-list></back></article>
