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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="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Journal of Clinical Practice</journal-id><journal-title-group><journal-title xml:lang="en">Journal of Clinical Practice</journal-title><trans-title-group xml:lang="ru"><trans-title>Клиническая практика</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2220-3095</issn><issn publication-format="electronic">2618-8627</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">632973</article-id><article-id pub-id-type="doi">10.17816/clinpract632973</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Case reports</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Клинические случаи</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">Outpatient regenerative therapy of a chronic diabetic foot ulcer with exposed bone surface</article-title><trans-title-group xml:lang="ru"><trans-title>Амбулаторная регенеративная терапия хронической раны диабетической стопы с открытыми костными поверхностями</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9459-7391</contrib-id><name-alternatives><name xml:lang="en"><surname>Pavlova</surname><given-names>Olga V.</given-names></name><name xml:lang="ru"><surname>Павлова</surname><given-names>Ольга Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>vasa-vasorum@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2705-3578</contrib-id><contrib-id contrib-id-type="spin">1046-8801</contrib-id><name-alternatives><name xml:lang="en"><surname>Kalsin</surname><given-names>Vladimir A.</given-names></name><name xml:lang="ru"><surname>Кальсин</surname><given-names>Владимир Анатольевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>vkalsin@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1180-2343</contrib-id><contrib-id contrib-id-type="spin">9211-6391</contrib-id><name-alternatives><name xml:lang="en"><surname>Konoplyannikov</surname><given-names>Mikhail A.</given-names></name><name xml:lang="ru"><surname>Коноплянников</surname><given-names>Михаил Анатольевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD, Cand. Sci. (Biol.)</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><email>mkonopl@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kuznetsova</surname><given-names>Sofia M.</given-names></name><name xml:lang="ru"><surname>Кузнецова</surname><given-names>София Марковна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>sophijka1010@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3033-5605</contrib-id><name-alternatives><name xml:lang="en"><surname>Baldin</surname><given-names>Victor L.</given-names></name><name xml:lang="ru"><surname>Балдин</surname><given-names>Виктор Львович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>baldinvl@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1867-6813</contrib-id><contrib-id contrib-id-type="spin">1054-4905</contrib-id><name-alternatives><name xml:lang="en"><surname>Sukhanova</surname><given-names>Yulia S.</given-names></name><name xml:lang="ru"><surname>Суханова</surname><given-names>Юлия Сергеевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>sukhanova.js@gmail.com</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3897-8306</contrib-id><contrib-id contrib-id-type="spin">5619-1151</contrib-id><name-alternatives><name xml:lang="en"><surname>Smirnov</surname><given-names>Alexander V.</given-names></name><name xml:lang="ru"><surname>Смирнов</surname><given-names>Александр Вячеславович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>alvsmirnov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1039-4245</contrib-id><contrib-id contrib-id-type="spin">3968-2971</contrib-id><name-alternatives><name xml:lang="en"><surname>Baklaushev</surname><given-names>Vladimir P.</given-names></name><name xml:lang="ru"><surname>Баклаушев</surname><given-names>Владимир Павлович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD</p></bio><bio xml:lang="ru"><p>д-р мед. наук</p></bio><email>baklaushev.vp@fnkc-fmba.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff3"/><xref ref-type="aff" rid="aff4"/><xref ref-type="aff" rid="aff5"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6209-4194</contrib-id><contrib-id contrib-id-type="spin">3240-4335</contrib-id><name-alternatives><name xml:lang="en"><surname>Ivanov</surname><given-names>Yuri V.</given-names></name><name xml:lang="ru"><surname>Иванов</surname><given-names>Юрий Викторович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Professor</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор</p></bio><email>ivanovkb83@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies</institution></aff><aff><institution xml:lang="ru">Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">First Sechenov Moscow State Medical University (Sechenov University)</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Russian National Research Medical University named after N.I. Pirogov</institution></aff><aff><institution xml:lang="ru">Российский национальный исследовательский медицинский университет имени Н.И. Пирогова</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">Federal Center of Brain Research and Neurotechnologies</institution></aff><aff><institution xml:lang="ru">Федеральный центр мозга и нейротехнологий</institution></aff></aff-alternatives><aff-alternatives id="aff5"><aff><institution xml:lang="en">Pulmonology Scientific Research Institute</institution></aff><aff><institution xml:lang="ru">Научно-исследовательский институт пульмонологии</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2024-06-30" publication-format="electronic"><day>30</day><month>06</month><year>2024</year></pub-date><pub-date date-type="pub" iso-8601-date="2024-07-15" publication-format="electronic"><day>15</day><month>07</month><year>2024</year></pub-date><volume>15</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>116</fpage><lpage>126</lpage><history><date date-type="received" iso-8601-date="2024-05-29"><day>29</day><month>05</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-06-26"><day>26</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-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://clinpractice.ru/clinpractice/article/view/632973">https://clinpractice.ru/clinpractice/article/view/632973</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND:</bold> Treatment of deep chronic wounds with the bone tissue involvement against the background of lower limb atherosclerosis and diabetic foot syndrome does not fit any reasonable hospital stay duration and at the same time has no effective outpatient methods. Therapy with conditioned medium derived from human mesenchymal stem cells (CM-MSC) may be a solution for this problem.</p> <p><bold>CLINICAL CASE DESCRIPTION:</bold> Patient F., 77-year-old, arrived for an outpatient treatment of local necrosis in the area of the 1st toe of the left foot in April, 2022. The main diagnosis: Peripheral arterial disease of the lower extremities. Multifocal atherosclerosis. Occlusion of the superficial femoral and popliteal arteries, diffuse lesions of the lower leg arteries on the left. Chronic arterial insufficiency of the 4th degree. Attempts of revascularisation of the left lower limb. Limited gangrene (Wagner IV) of the 1st toe of the left foot. Associated diseases: insulin-dependent type 2 diabetes mellitus (for more than 30 years). Diabetic polyneuropathy. Diabetic foot syndrome, neurotrophic form. Local treatment was performed by the microsurgical debridement of the affected surface in combination with the method of multilayered dressings, according to the previously patented technology. The microsurgical treatment of the bone surface in the wound area was carried out with the use of CM-MSC. Positive dynamics in the form of a partial closure of the bone fragment with soft tissue was observed on the sixth month of therapy. The complete closure of the open bone fragment was observed in 12 months from the beginning of the outpatient treatment.</p> <p><bold>CONCLUSION:</bold> The developed method of treatment using CM-MSC can be effective for chronic wounds with open bone surfaces.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Обоснование.</bold> Лечение глубоких хронических ран с вовлечением костной ткани на фоне атеросклероза нижних конечностей и синдрома диабетической стопы не укладывается ни в какие сроки стационарной терапии и при этом не имеет эффективных амбулаторных методов. Решением этой проблемы может быть терапия с помощью кондиционированной мезенхимальными стволовыми клетками среды (КС-МСК).</p> <p><bold>Описание клинического случая.</bold> Пациентка Ф., 77 лет, с локальным некрозом в области I пальца левой стопы обратилась за амбулаторным лечением в апреле 2022 года. Основной диагноз: «Атеросклероз периферических сосудов нижних конечностей. Мультифокальный атеросклероз. Окклюзия поверхностной бедренной и подколенной артерий, диффузное поражение артерий голени слева. Хроническая артериальная недостаточность IV степени. Попытки реваскуляризации левой нижней конечности. Ограниченная гангрена (Wagner IV) I пальца левой стопы». Сопутствующие заболевания: сахарный диабет 2-го типа, инсулинопотребный (стаж более 30 лет). Диабетическая полинейропатия. Синдром диабетической стопы, нейротрофическая форма. Проведено местное лечение путём микрохирургического дебридмента поражённой поверхности в сочетании с методом многоярусных повязок, согласно запатентованной ранее технологии. Микрохирургическую обработку костной поверхности в области раны проводили с применением КС-МСК. Уже на 6-м месяце терапии наблюдалась положительная динамика в виде частичного закрытия костного фрагмента мягкими тканями. Полное закрытие открытого костного фрагмента наблюдалось через 12 месяцев от начала лечения в амбулаторных условиях.</p> <p><bold>Заключение.</bold> Разработанный нами метод лечения с помощью КС-МСК может быть эффективен в амбулаторной терапии хронических ран с открытыми костными поверхностями.</p></trans-abstract><kwd-group xml:lang="en"><kwd>lower limb amputation</kwd><kwd>critical ischemia of the lower limb</kwd><kwd>cell conditioned medium</kwd><kwd>chronic wound</kwd><kwd>diabetes mellitus</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>ампутация нижних конечностей</kwd><kwd>критическая ишемия нижней конечности</kwd><kwd>кондиционированная клеточная среда</kwd><kwd>хроническая рана</kwd><kwd>сахарный диабет</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Правительство РФ</institution></institution-wrap><institution-wrap><institution xml:lang="en">Government of the Russian Federation</institution></institution-wrap></funding-source></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Miyanaga T, Haseda Y, Daizo H, et al. A perifascial areolar tissue graft with topical administration of basic fibroblast growth factor for treatment of complex wounds with exposed tendons and/or bones. J Foot Ankle Surg. 2018;57(1):104–110. doi: 10.1053/j.jfas.2017.08.026</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Magliano DJ, Boyko EJ; IDF Diabetes Atlas 10th edition scientific committee. Brussels: International Diabetes Federation; 2021. Chapter 3, Global picture. Режим доступа: https://www.ncbi.nlm.nih.gov/books/NBK581940/. Дата обращения: 15.04.2024.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Canavan RJ, Unwin NC, Kelly WF, Connolly VM. Diabetes- and nondiabetes-related lower extremity amputation incidence before and after the introduction of better organized diabetes foot care: Continuous longitudinal monitoring using a standard method. Diabetes Care. 2008;31(3):459–463. doi: 10.2337/dc07-1159</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Chen SL, Chen TM, Chou TD, et al. The distally based lesser saphenous venofasciocutaneous flap for ankle and heel reconstruction. Plast Reconstr Surg. 2002;110(7):1664–1672. doi: 10.1097/01.PRS.0000033025.43603.67</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Parodi PC, Biasio FD, Rampino E, et al. The distally-based radial fasciosubcutaneous flap for soft tissue cover of the flexor aspect of the wrist. Scand J Plast Reconstr Surg Hand Surg. 2003;37(1):61–63. doi: 10.1080/alp.37.1.61.63</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Chen SL, Chen TM, Wang HJ. The distally based sural fasciomusculocutaneous flap for foot reconstruction. J Plast Reconstr Aesthet Surg. 2006;59(8):846–855. doi: 10.1016/j.bjps.2005.10.013</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Hallock GG. Free-flap coverage of the exposed Achilles tendon. Plast Reconstr Surg. 1989;83(4):710–716. doi: 10.1097/00006534-198904000-00019</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Ларичев А.Б., Чистяков А.Л., Комлев В.Л. Сравнительная оценка заживления раны при использовании локального лоскута и полнослойного кожного трансплантата в реконструктивно-восстановительной хирургии головы и шеи // Раны и раневые инфекции. Журнал имени проф. Б.М. Костючёнка. 2016. Т. 3, № 2. С. 37–46. [Larichev AB, Chistyakov AL, Komlev VL. Comparative assessment of wound healing by using a local flap and full-thickness skin graft in reconstructive head and neck surgery. Wounds and wound infections. The prof. B.M. Kostyuchenok journal. 2016;3(2):37–46. (In Russ).] EDN: XCNXVR doi: 10.17650/2408-9613-2016-3-2-37-46</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Nakamichi M, Akishima Y, Fujisawa C, et al. Basic fibroblast growth factor induces angiogenic properties of fibrocytes to stimulate vascular formation during wound healing. Am J Pathol. 2016;186(12):3201–3216. doi: 10.1016/j.ajpath.2016.08.015</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Suzuki S, Kawai K, Ashoori F, et al. Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge. Br J Plast Surg. 2000;53(8):659–666. doi: 10.1054/bjps.2000.3426</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Chen X, Chen H, Zhang G. Management of wounds with exposed bone structures using an artificial dermis and skin grafting technique. Clin Plast Surg. 2012;39(1):69–75. doi: 10.1016/j.cps.2011.09.011</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Pittenger MF, Discher DE, Péault BM, et al. Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regen Med. 2019;(4):22. EDN: MXZCWM doi: 10.1038/s41536-019-0083-6</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Otero-Viñas M, Falanga V. Mesenchymal stem cells in chronic wounds: The spectrum from basic to advanced therapy. Adv Wound Care (New Rochelle). 2016;5(4):149–163. doi: 10.1089/wound.2015.0627</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Heydari MB, Ghanbari-Movahed Z, Heydari M, Farzaei MH. In vitro study of the mesenchymal stem cells-conditional media role in skin wound healing process: A systematic review. Int Wound J. 2022;19(8):2210–2223. EDN: SRZLNT doi: 10.1111/iwj.13796</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Ma H, Siu WS, Leung PC. The potential of MSC-based cell-free therapy in wound healing: A thorough literature review. Int J Mol Sci. 2023;24(11):9356. EDN: YJPOQS doi: 10.3390/ijms24119356</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Bogatcheva NV, Coleman ME. Conditioned medium of mesenchymal stromal cells: A new class of therapeutics. Biochem (Mosc). 2019;84(11):1375–1389. EDN: ZRULLM doi: 10.1134/S0006297919110129</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Патент РФ на изобретение № RU2575780 C1. Павлова О.В. Способ микрохирургической обработки длительно незаживающих хронических ран. [Patent RUS № RU2575780 C1. Pavlova OV. Method of microsurgical treatment of long non-healing chronic wounds. (In Russ).] Режим доступа: https://yandex.ru/patents/doc/RU2575780C1_20160220. Дата обращения: 15.04.2024.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Bates-Jensen BM, McCreath HE, Harputlu D, Patlan A. Reliability of the Bates-Jensen wound assessment tool for pressure injury assessment: The pressure ulcer detection study. Wound Repair Regen. 2019;27(4):386–395. doi: 10.1111/wrr.12714</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Saheli M, Bayat M, Ganji R, et al. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Arch Dermatol Res. 2020;312(5):325–336. EDN: WTLEWO doi: 10.1007/s00403-019-02016-6</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Темнов А.А., Астрелина Т.А., Рогов К.А., и др. Исследование влияния факторов кондиционной среды, полученной при культивировании мезенхимальных стволовых клеток костного мозга, на течение тяжелых местных лучевых поражений кожи у крыс // Медицинская радиология и радиационная безопасность. 2018. № 1. С. 35–43. [Temnov AA, Astrelina TA, Rogov KA, et al. Investigation of the influence of the conditioning medium factors obtained during the cultivation of bone marrow mesenchymal stem cells on the course of severe local radiation injuries of skin in rats. Мedical Radiology and Radiation Safety. 2018;(1):35–43. (In Russ).] EDN: YTGIIB doi: 10.12737/article_5a82eb9a9bbac1.67972336</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Montero-Vilchez T, Sierra-Sánchez Á, Sanchez-Diaz M, et al. Mesenchymal stromal cell-conditioned medium for skin diseases: A systematic review. Front Cell Dev Biol. 2021;(9):654210. EDN: TQWLTX doi: 10.3389/fcell.2021.654210</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Marofi F, Alexandrovna KI, Margiana R, et al. MSCs and their exosomes: A rapidly evolving approach in the context of cutaneous wounds therapy. Stem Cell Res Ther. 2021;12(1):597. EDN: VKILLO doi: 10.1186/s13287-021-02662-6</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Therapeutic potential of stem cell conditioned medium on chronic ulcer wounds [2020 June 22]. Режим доступа: https://clinicaltrials.gov/study/NCT04134676?term=NCT04134676. Дата обращения: 15.04.2024.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Черепанин А.И., Павлова О.В., Кальсин В.А., и др. Клинический случай успешного применения кондиционированной клеточной среды для лечения хронической раны ампутационной культи // Клиническая практика.2022. Т. 13, № 1. С. 92–98. [Cherepanin AI, Pavlova OV, Kalsin VA, et al. Successful application of conditioned culture medium for the treatment of a chronic wound of an amputation stump: A clinical case. J Clinical Practice. 2022;13(1):92–98. (In Russ).] EDN: WTJHAW doi: 10.17816/clinpract105089</mixed-citation></ref></ref-list></back></article>
