<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<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="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Traumatology and Orthopedics of Russia</journal-id><journal-title-group><journal-title xml:lang="en">Traumatology and Orthopedics of Russia</journal-title><trans-title-group xml:lang="ru"><trans-title>Травматология и ортопедия России</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2311-2905</issn><issn publication-format="electronic">2542-0933</issn><publisher><publisher-name xml:lang="en">Vreden National Medical Research Center of Traumatology and Orthopedics</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">17519</article-id><article-id pub-id-type="doi">10.17816/2311-2905-17519</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Theoretical and experimental studies</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Теоретические и экспериментальные исследования</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="zh"><subject>Theoretical and experimental studies</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Risk of thromboembolism after intraosseous implantation of metallic devices with extracellular vesicles derived from multipotent stromal cells: preliminary results</article-title><trans-title-group xml:lang="ru"><trans-title>Риск тромбоэмболии после внутрикостной имплантации металлических изделий с экстрацеллюлярными везикулами мультипотентных стромальных клеток: предварительные результаты</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title/></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8182-5084</contrib-id><name-alternatives><name xml:lang="en"><surname>Maiborodin</surname><given-names>Igor V.</given-names></name><name xml:lang="ru"><surname>Майбородин</surname><given-names>Игорь Валентинович</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci (Med.), Professor</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор</p></bio><email>imai@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5279-3650</contrib-id><name-alternatives><name xml:lang="en"><surname>Ryaguzov</surname><given-names>Maksim E.</given-names></name><name xml:lang="ru"><surname>Рягузов</surname><given-names>Максим Евгеньевич</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci (Med.)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>rymax@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9046-0099</contrib-id><name-alternatives><name xml:lang="en"><surname>Kuzkin</surname><given-names>Sergey A.</given-names></name><name xml:lang="ru"><surname>Кузькин</surname><given-names>Сергей Александрович</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci (Med.)</p></bio><bio xml:lang="ru"><p>канд. мед. наук, Институт молекулярной патологии и патоморфологии</p></bio><email>acutus@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9235-9384</contrib-id><name-alternatives><name xml:lang="en"><surname>Shevela</surname><given-names>Aleksandr A.</given-names></name><name xml:lang="ru"><surname>Шевела</surname><given-names>Александр Андреевич</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci (Med.)</p></bio><bio xml:lang="ru"><p>д-р мед. наук</p></bio><email>mdshevela@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-4140-3531</contrib-id><name-alternatives><name xml:lang="en"><surname>Sheplev</surname><given-names>Boris V.</given-names></name><name xml:lang="ru"><surname>Шеплев</surname><given-names>Борис Валентинович</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci (Med.)</p></bio><bio xml:lang="ru"><p>д-р мед. наук</p></bio><email>shepa@icloud.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9409-4823</contrib-id><name-alternatives><name xml:lang="en"><surname>Marinkin</surname><given-names>Igor O.</given-names></name><name xml:lang="ru"><surname>Маринкин</surname><given-names>Игорь Олегович</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci (Med.), Professor</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор</p></bio><email>rector@ngmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5169-6373</contrib-id><name-alternatives><name xml:lang="en"><surname>Maiborodina</surname><given-names>Vitalina I.</given-names></name><name xml:lang="ru"><surname>Майбородина</surname><given-names>Виталина Игоревна</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci (Med.)</p></bio><bio xml:lang="ru"><p>д-р мед. наук</p></bio><email>mai_@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3269-2465</contrib-id><name-alternatives><name xml:lang="en"><surname>Lushnikova</surname><given-names>Elena L.</given-names></name><name xml:lang="ru"><surname>Лушникова</surname><given-names>Елена Леонидовна</given-names></name><name xml:lang="zh"><surname></surname><given-names></given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci (Biol.), Professor</p></bio><bio xml:lang="ru"><p>д-р биол. наук, профессор, Институт молекулярной патологии и патоморфологии</p></bio><email>pathol@inbox.ru</email><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences</institution></aff><aff><institution xml:lang="ru">ФГБУН «Институт химической биологии и фундаментальной медицины Сибирского отделения РАН»</institution></aff><aff><institution xml:lang="zh"></institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Federal Research Center for Fundamental and Translational Medicine</institution></aff><aff><institution xml:lang="ru">ФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины» Минобрнауки России РФ</institution></aff><aff><institution xml:lang="zh"></institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2024-07-04" publication-format="electronic"><day>04</day><month>07</month><year>2024</year></pub-date><volume>30</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><issue-title xml:lang="zh"/><fpage>131</fpage><lpage>142</lpage><history><date date-type="received" iso-8601-date="2024-04-03"><day>03</day><month>04</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-06-07"><day>07</day><month>06</month><year>2024</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2024,</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</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-nc-nd/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://journal.rniito.org/jour/article/view/17519">https://journal.rniito.org/jour/article/view/17519</self-uri><abstract xml:lang="en"><p><bold>Background.</bold> New implantation methods are of great importance due to the development of endoprostheses in traumatology and orthopedics, restorative medicine and dentistry. Equally important is the early detection and description of the implant-associated complications.</p> <p><bold>The aim of the study</bold> is to find and describe thrombi and emboli in the heart and lungs formed after experimental implantation of metallic devices in the peripheral part of limb using extracellular vesicles of mesenchymal stromal cells.</p> <p><bold>Methods.</bold> Outbred rabbits of both genders at the age from 4 to 6 months and of weight from 3 to 4 kg underwent experimental implantation. The study enrolled 57 species in total. They were divided into two groups: 30 animals underwent implantation of metallic devices using extracellular vesicles of mesenchymal stromal cells (EV MSCs), 27 — without their use. The rabbits’ hearts and lungs were studied by light microscopy methods at different stages after integration of screw titanium implants into the proximal condyle of the tibia using EV MSCs.</p> <p><bold>Results. </bold>After implantation of metallic devices into the proximal condyle of the tibia, we detected fibrin, detritus and even the red bone marrow structures (various blast forms of hematopoietic cells: megakaryocytes, cells of the erythroid and myeloid lineages) in the right cavities of the heart. In the pulmonary arteries, we also found thrombi and emboli, which either led to the obliteration of the involved vessel or to gradual lysis, not disappearing completely within 10 days of follow-up.</p> <p><bold>Conclusions.</bold> After intraosseous implantation of the metallic devices, there is an embolism risk in the right atria and ventricle of the heart and the pulmonary arteries and veins due to the debris migration with the bloodstream from the surgery site. At the same time, one cannot exclude a thrombotic risk in the heart and pulmonary arteries as a reaction to the presence of detritus. It is advisable to take measures aimed at preventing both debris releasing into the bloodstream and pulmonary embolism during any implantations into the bone tissues, even of relatively small devices. Using EV MSCs to affect the implant engraftment processes has no significant effect on the severity and frequency of thromboembolic complications.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Актуальность.</bold> Новые методы имплантации имеют большое значение в связи с созданием эндопротезов в травматологии и ортопедии, восстановительной медицине и стоматологии. Не менее важно своевременное выявление и описание осложнений применения различных имплантационных процедур.</p> <p><bold>Цель исследования </bold>— найти и описать тромбы и эмболы в сердце и легких после экспериментальной имплантации металлических изделий в периферический отдел конечности с применением экстрацеллюлярных везикул мезенхимных стромальных клеток.</p> <p><bold>Материал и методы.</bold> Экспериментальная имплантация была проведена беспородным кроликам обоего пола в возрасте 4–6 мес. массой 3–4 кг. Общее количество животных, включенных в исследование, составило 57 особей. Они были разделены на группы: 30 животным металлические изделия имплантировали с применением экстрацеллюлярных везикул мезенхимных стромальных клеток (ЭВ МСК), 27 — без их применения. Методами световой микроскопии изучали сердца и легкие кроликов в различные сроки после имплантации винтовых титановых имплантатов в проксимальный мыщелок большеберцовой кости (ПМБК) с использованием ЭВ МСК.</p> <p><bold>Результаты.</bold> После внедрения металлического изделия в ПМБК в правых полостях сердца были обнаружены фибрин, детрит и даже структуры красного костного мозга (различные бластные формы гемопоэтических клеточных элементов: мегакариоциты, клетки эритроидного и миелоидного ростков). В артериях легких также были найдены тромбы и эмболы, которые или приводили к облитерации задействованного сосуда, или постепенно лизировались, но полностью не исчезали в течение 10 сут. наблюдения.</p> <p><bold>Заключение.</bold> После внутрикостной имплантации существует вероятность эмболии правых предсердия и желудочка сердца и сосудов легких вследствие миграции дебриса с током крови из места операции. Вместе с этим не исключено тромбообразование в сердце и артериях легких как реакция на присутствие детрита. Является целесообразным принятие мер, направленных как на недопущение попадания дебриса в кровоток, так и на профилактику тромбоэмболии легочной артерии при любых имплантациях в костные ткани, даже относительно небольших изделий. Применение экстрацеллюлярных везикул мезенхимных стромальных клеток для воздействия на процессы приживления имплантатов в значительной степени не влияет на выраженность и частоту тромбоэмболических осложнений.</p></trans-abstract><trans-abstract xml:lang="zh"><p/></trans-abstract><kwd-group xml:lang="en"><kwd>intraosseous implantation metallic devices</kwd><kwd>extracellular vesicles derived from mesenchymal stromal cells</kwd><kwd>thrombosis</kwd><kwd>cardiac thromboembolism</kwd><kwd>pulmonary thromboembolism</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>внутрикостная имплантация</kwd><kwd>экстрацеллюлярные везикулы мезенхимных стромальных клеток</kwd><kwd>тромбоз</kwd><kwd>тромбоэмболия сердца</kwd><kwd>тромбоэмболия легочных артерий</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">ИХБФМ СО РАН</institution></institution-wrap><institution-wrap><institution xml:lang="en">ICBFM SB RAS</institution></institution-wrap></funding-source><award-id>121031300045-2</award-id></award-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">ПФНИ ГАН</institution></institution-wrap><institution-wrap><institution xml:lang="en">PFNI GAN</institution></institution-wrap></funding-source><award-id>122032300164-6</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Li T., Wang Q., Wang W., Yang J., Dong S. One filter may be enough for duplicate inferior vena cava filter implantation in patients with deep venous thrombosis: Two cases report. Medicine (Baltimore). 2022;101(52): e32480. doi: 10.1097/MD.0000000000032480.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Shah K.J., Roy T.L. Catheter-Directed Interventions for the Treatment of Lower Extremity Deep Vein Thrombosis. Life (Basel). 2022;12(12):1984. doi: 10.3390/life12121984.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Marques M.A., Fiorelli S.K.A., Barros B.C.S., Ribeiro A.J.A., Ristow A.V., Fiorelli R.K.A. Protocol for prophylaxis of venous thromboembolism in varicose vein surgery of the lower limbs. Rev Col Bras Cir. 2022;49:e20223326. doi: 10.1590/0100-6991e-20223326-en.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Bharti N., Mahajan S. Massive pulmonary embolism leading to cardiac arrest after tourniquet deflation following lower limb surgery. Anaesth Intensive Care. 2009;37(5):867-868.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Drouin L., Pistorius MA., Lafforgue A., N’Gohou C., Richard A., Connault J. et al. Upper-extremity venous thrombosis: A retrospective study about 160 cases. Rev Med Interne. 2019;40(1):9-15. (In French). doi: 10.1016/j.revmed.2018.07.012.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Khan O., Marmaro A., Cohen D.A. A review of upper extremity deep vein thrombosis. Postgrad Med. 2021;133(sup1):3-10. doi: 10.1080/00325481.2021.1892390.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Duan Y., Wang G.L., Guo X., Yang LL., Tian F.G. Acute pulmonary embolism originating from upper limb venous thrombosis following breast cancer surgery: Two case reports. World J Clin Cases. 2022;10(21):7445-7450. doi: 10.12998/wjcc.v10.i21.7445.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Major K.M., Bulic S., Rowe V.L., Patel K., Weaver F.A. Internal jugular, subclavian, and axillary deep venous thrombosis and the risk of pulmonary embolism. Vascular. 2008;16(2):73-79. doi: 10.2310/6670.2008.00019.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Kim S., Ahn H., Shin S.A., Park J.H., Won C.W. Trends of thromboprophylaxis and complications after major lower limb orthopaedic surgeries in Korea: National Health Insurance Claim Data. Thromb Res. 2017;155:48-52. doi: 10.1016/j.thromres.2017.04.023.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Heijboer R.R.O., Lubberts B., Guss D., Johnson A.H., DiGiovanni C.W. Incidence and Risk Factors Associated with Venous Thromboembolism After Orthopaedic Below-knee Surgery. J Am Acad Orthop Surg. 2019;27(10):e482-e490. doi: 10.5435/JAAOS-D-17-00787.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Gurunathan U., Barras M., McDougall C., Nandurkar H., Eley V. Obesity and the Risk of Venous Thromboembolism after Major Lower Limb Orthopaedic Surgery: A Literature Review. Thromb Haemost. 2022; 122(12):1969-1979. doi: 10.1055/s-0042-1757200.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Grandi G., Antonini E., Bianchi C. Pulmonary bone-marrow embolism. Analysis of 53 cases. Minerva Med. 1978;69(8):491-494. (In Italian).</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Orlowski J.P., Julius C.J., Petras R.E., Porembka D.T., Gallagher J.M. The safety of intraosseous infusions: risks of fat and bone marrow emboli to the lungs. Ann Emerg Med. 1989;18(10):1062-1067. doi: 10.1016/s0196-0644(89)80932-1.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Kemona A., Nowak H.F., Dziecioł J., Sulik M., Sulkowski S. Pulmonary bone marrow embolism in nonselected autopsy material. Patol Pol. 1989;40(2): 197-204. (In Polish).</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Koessler M.J., Pitto R.P. Fat and bone marrow embolism in total hip arthroplasty. Acta Orthop Belg. 2001;67(2):97-109.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Issack P.S., Lauerman M.H., Helfet D.L., Sculco T.P., Lane J.M. Fat embolism and respiratory distress associated with cemented femoral arthroplasty. Am J Orthop (Belle Mead NJ). 2009;38(2):72-76.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Sharma P., Gautam A., Kumar P., Malhotra P., Nada R., Ahluwalia J. Bone marrow emboli following bone marrow procedure: A possible complication. Indian J Pathol Microbiol. 2022;65(4):946-947. doi: 10.4103/ijpm.ijpm_442_21.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Maiborodin I., Shevela A., Matveeva V., Morozov V., Toder M., Krasil’nikov S. et al. First Experimental Study of the Influence of Extracellular Vesicles Derived from Multipotent Stromal Cells on Osseointegration of Dental Implants. Int J Mol Sci. 2021;22(16):8774. doi: 10.3390/ijms22168774.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Maiborodin I., Shevela A., Toder M., Marchukov S., Tursunova N., Klinnikova M. et al. Multipotent Stromal Cell Extracellular Vesicle Distribution in Distant Organs after Introduction into a Bone Tissue Defect of a Limb. Life (Basel). 2021;11(4):306. doi: 10.3390/life11040306.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Maiborodin I., Klinnikova M., Kuzkin S., Maiborodina V., Krasil’nikov S., Pichigina A. et al. Morphology of the Myocardium after Experimental Bone Tissue Trauma and the Use of Extracellular Vesicles Derived from Mesenchymal Multipotent Stromal Cells. J Pers Med. 2021;11(11):1206. doi: 10.3390/jpm11111206.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Coipeau P., Rosset P., Langonne A., Gaillard J., Delorme B., Rico A. et al. Impaired differentiation potential of human trabecular bone mesenchymal stromal cells from elderly patients. Cytotherapy. 2009;11(5):584-594. doi: 10.1080/14653240903079385.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Martins A.A., Paiva A., Morgado J.M., Gomes A., Pais M.L. Quantification and immunophenotypic characterization of bone marrow and umbilical cord blood mesenchymal stem cells by multicolor flow cytometry. Transplant Proc. 2009;41(3):943-946. doi: 10.1016/j.transproceed.2009.01.059.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Berner A., Siebenlist S., Reichert J.C., Hendrich C., Nöth U. Reconstruction of osteochondral defects with a stem cell-based cartilage-polymer construct in a small animal model. Z Orthop Unfall. 2010;148(1):31-38. (In German). doi: 10.1055/s-0029-1240753.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Zhao J., Xu J.J. Experimental study on application of polypropylene hernia of fat stem cells in rats. Eur Rev Med Pharmacol Sci. 2018;22(18):6156-6161. doi: 10.26355/eurrev_201809_15957.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Blazquez R., Sanchez-Margallo F.M., de la Rosa O., Dalemans W., Alvarez V., Tarazona R. et al. Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol. 2014;5:556. doi: 10.3389/fimmu.2014.00556.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Oshchepkova A., Neumestova A., Matveeva V., Artemyeva L., Morozova K., Kiseleva E. et al. Cytochalasin-B-inducible nanovesicle mimics of natural extracellular vesicles that are capable of nucleic acid transfer. Micromachines (Basel). 2019;10(11):750. doi: 10.3390/mi10110750.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Lin Y., Zhang F., Lian X.F., Peng W.Q., Yin C.Y. Mesenchymal stem cell-derived exosomes improve diabetes mellitus-induced myocardial injury and fibrosis via inhibition of TGF-β1/Smad2 signaling pathway. Cell Mol Biol (Noisy-le-grand). 2019;65(7):123-126.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Liang P., Ye F., Hou C.C., Pi L., Chen F. Mesenchymal stem cell therapy for patients with ischemic heart failure – past, present, and future. Curr Stem Cell Res Ther. 2021;16(5):608-621. doi: 10.2174/1574888X15666200309144906.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Sadallah S., Eken C., Schifferli J.A. Ectosomes as modulators of inflammation and immunity. Clin Exp Immunol. 2011;163(1):26-32. doi: 10.1111/j.1365-2249.2010.04271.x.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Silachev D.N., Goryunov K.V., Shpilyuk M.A., Beznoschenko O.S., Morozova N.Y., Kraevaya E.E. et al. Effect of MSCs and MSC-derived extracellular vesicles on human blood coagulation. Cells. 2019;8(3):258. doi: 10.3390/cells8030258.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Tang X.D., Shi L., Monsel A., Li X.Y., Zhu H.L., Zhu Y.G. et al. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang-1 mRNA. Stem Cells. 2017;35(7):1849-1859. doi: 10.1002/stem.2619.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Haga H., Yan I.K., Borrelli D.A., Matsuda A., Parasramka M., Shukla N. et al. Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury. Liver Transpl. 2017;23(6):791-803. doi: 10.1002/lt.24770.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Toh W.S., Lai R.C., Hui J.H.P., Lim S.K. MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. Semin. Cell Dev Biol. 2017;67:56-64. doi: 10.1016/j.semcdb.2016.11.008.</mixed-citation></ref></ref-list></back></article>
