vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2017-4-88-96vtio-832Research ArticleРегенеративная медицина и клеточные технологииRegenerative Medicine and Cell TechnologiesЭффекты ингаляционного и внутривенного введения аллогенных мезенхимальных стромальных клеток костного мозга в блеомицин-индуцированной модели легочного фиброза у кроликовEffects of inhalation and intravenous administration of allogeneic mesenchymal bone marrow stromal cells in a bleomycin-induced model of pulmonary fibrosis in rabbitsАверьяновА. В.AveryanovA. V.

Москва.

Moscow.

averyanovav@mail.ruКоноплянниковА. Г.KonoplyannikovA. G.

Обнинск.

Obninsk.

ЗабозлаевФ. Г.ZabozlaevF. G.

Москва.

Moscow.

ДанилевскаяО. В.DanilevskayaO. V.

Москва.

Moscow.

КоноплянниковМ. А.KonoplyannikovM. A.

Москва.

Moscow.

СорокинаА. В.SorokinaA. V.

Москва.

Moscow.

КоролеваИ. А.KorolevaI. A.

Москва.

Moscow.

АнтоновН. С.AntonovN. S.

Москва.

Moscow.

ОсиповаГ. Л.OsipovaG. L.

Москва.

Moscow.

ВасильеваО. С.VasilyevaO. S.

Москва.

Moscow.

СахароваГ. М.SakharovaG. M.

Москва.

Moscow.

ТатарскийА. Р.TatarskyA. R.

Москва.

Moscow.

КобылянскийВ. И.KobylianskiiV. I.

Москва.

Moscow.

РомановВ. В.RomanovV. V.

Москва.

Moscow.

СтепанянИ. Э.StepanyanI. E.

Москва.

Moscow.

БабакС. Л.BabakS. L.

Москва.

Moscow.

ТроицкийА. В.TroitskyA. V.

Москва.

Moscow.

ФГБУ «Научно-исследовательский институт пульмонологии» ФМБА России; ФГБУ «Федеральный научно-клинический центр» ФМБА России.РоссияPulmonology Research Institute under FMBA of Russia; Federal Research Clinical Center under FMBA of Russia.Russian FederationФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России.РоссияNational Medical Radiology Research Center, Ministry of Health of Russia.Russian FederationФГБУ «Федеральный научно-клинический центр» ФМБА России.РоссияFederal Research Clinical Center under FMBA of Russia.Russian FederationФГБУ «Научно-исследовательский институт пульмонологии» ФМБА России.РоссияPulmonology Research Institute under FMBA of Russia.Russian FederationФГБНУ «Центральный научно-исследовательский институт туберкулеза».РоссияCentral Tuberculosis Research Institute.Russian Federation2017310120181948896Copyright © Аверьянов А.В., Коноплянников А.Г., Забозлаев Ф.Г., Данилевская О.В., Коноплянников М.А., Сорокина А.В., Королева И.А., Антонов Н.С., Осипова Г.Л., Васильева О.С., Сахарова Г.М., Татарский А.Р., Кобылянский В.И., Романов В.В., Степанян И.Э., Бабак С.Л., Троицкий А.В., 20182018Аверьянов А.В., Коноплянников А.Г., Забозлаев Ф.Г., Данилевская О.В., Коноплянников М.А., Сорокина А.В., Королева И.А., Антонов Н.С., Осипова Г.Л., Васильева О.С., Сахарова Г.М., Татарский А.Р., Кобылянский В.И., Романов В.В., Степанян И.Э., Бабак С.Л., Троицкий А.В.Averyanov A.V., Konoplyannikov A.G., Zabozlaev F.G., Danilevskaya O.V., Konoplyannikov M.A., Sorokina A.V., Koroleva I.A., Antonov N.S., Osipova G.L., Vasilyeva O.S., Sakharova G.M., Tatarsky A.R., Kobylianskii V.I., Romanov V.V., Stepanyan I.E., Babak S.L., Troitsky 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://journal.transpl.ru/vtio/article/view/832

Проведен сравнительный анализ эффективности ингаляционного и внутривенного пути доставки эквивалентных доз мезенхимальных стромальных клеток костного мозга у кроликов на стандартной модели блеомицинового легочного фиброза. После бронхоскопической инсталляции блеомицина в заднюю правую долю 5 кроликов получили внутривенную трансплантацию 2 × 106 аллогенных МСК, 5 – 2 × 107 МСК ингаляционно через компрессорный небулайзер; по 5 животных использовались в качестве здорового и блеомицинового контроля без лечения.

Результаты

Результаты. Обе группы, получавшие лечение МСК, имели достоверно более низкий индекс фиброза по морфометрической шкале Эшкрофта, чем контрольная группа блеомицинового фиброза. Экспрессия коллагена в ткани легких была существенно выше во всех группах с блеомициновой травмой, но у животных, подвергшихся внутривенной трансплантации МСК, она составила 0,79 балла, а при ингаляционном введении – 0,51 балла, тогда как группа блеомицина без лечения – 2,1 балла. Уровни TNF-α и TGF-β1в жидкости БАЛ имели тенденцию к уменьшению в группах лечения, но достоверно не различались от контроля. Похожая картина имела место при цитологическом анализе БАЛ.

Выводы

Выводы. В целом оба метода доставки клеточного материала в легкие продемонстрировали сходные терапевтические эффекты в отношении сдерживания развития экспериментального фиброза, существенно не отличаясь между собой, что свидетельствует о возможности использования как внутривенного, так и ингаляционного пути введения для последующих клинических исследований. 

Aim

Aim: to perform a comparative analysis of the effi cacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fi brosis.

Materials and methods

Materials and methods. After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × 106 allogeneic BMMSCs, other 5 rabbits – 2 × 107 MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each.

Results

Results. Both groups treated with BMMSCs had a signifi cantly lower Ashcroft fi brosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Levels of TNF-α and TGF-β1 in BAL fl uids tended to decrease in treatment groups, but did not differ signifi cantly from control. A similar picture was observed in the cytological analysis of BAL.

Conclusion

Conclusion. In general, both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fi brosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies. 

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