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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">Morphology</journal-id><journal-title-group><journal-title xml:lang="en">Morphology</journal-title><trans-title-group xml:lang="ru"><trans-title>Морфология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1026-3543</issn><issn publication-format="electronic">2949-2556</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">681777</article-id><article-id pub-id-type="doi">10.17816/morph.681777</article-id><article-id pub-id-type="edn">YIPDKS</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original Study Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</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">Gene expression of cytokines and wound-healing potential of macrophages derived from rat bone marrow and peripheral blood</article-title><trans-title-group xml:lang="ru"><trans-title>Экспрессия генов цитокинов и ранозаживляющий потенциал макрофагов, полученных из красного костного мозга и периферической крови крыс</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>大鼠红骨髓和外周血来源巨噬细胞的细胞因子基因表达和伤口愈合潜能</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3001-4820</contrib-id><contrib-id contrib-id-type="spin">2698-1448</contrib-id><name-alternatives><name xml:lang="en"><surname>Kiseleva</surname><given-names>Viktoriia V.</given-names></name><name xml:lang="ru"><surname>Киселева</surname><given-names>Виктория Викторовна</given-names></name><name xml:lang="zh"><surname>Kiseleva</surname><given-names>Viktoriia V.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>victoria.kurnosova.1991@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8650-8240</contrib-id><contrib-id contrib-id-type="spin">3406-3866</contrib-id><name-alternatives><name xml:lang="en"><surname>Vishnyakova</surname><given-names>Polina A.</given-names></name><name xml:lang="ru"><surname>Вишнякова</surname><given-names>Полина Александровна</given-names></name><name xml:lang="zh"><surname>Vishnyakova</surname><given-names>Polina A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Biology), Assistant Professor</p></bio><bio xml:lang="ru"><p>канд. биол. наук, доцент</p></bio><bio xml:lang="zh"><p>Cand. Sci. (Biology), Assistant Professor</p></bio><email>vpa2002@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0946-1105</contrib-id><contrib-id contrib-id-type="spin">6842-0264</contrib-id><name-alternatives><name xml:lang="en"><surname>Tsvetkov</surname><given-names>Ivan S.</given-names></name><name xml:lang="ru"><surname>Цветков</surname><given-names>Иван Сергеевич</given-names></name><name xml:lang="zh"><surname>Tsvetkov</surname><given-names>Ivan S.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Biology)</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><bio xml:lang="zh"><p>Cand. Sci. (Biology)</p></bio><email>davedm66@gmail.com</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2392-4439</contrib-id><contrib-id contrib-id-type="spin">5160-9029</contrib-id><name-alternatives><name xml:lang="en"><surname>Elchaninov</surname><given-names>Andrey V.</given-names></name><name xml:lang="ru"><surname>Ельчанинов</surname><given-names>Андрей Владимирович</given-names></name><name xml:lang="zh"><surname>Elchaninov</surname><given-names>Andrey V.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Biology), Assistant Professor</p></bio><bio xml:lang="ru"><p>д-р биол. наук, доцент</p></bio><bio xml:lang="zh"><p>Dr. Sci. (Biology), Assistant Professor</p></bio><email>elchandrey@yandex.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6182-1799</contrib-id><contrib-id contrib-id-type="spin">5421-5520</contrib-id><name-alternatives><name xml:lang="en"><surname>Kosyreva</surname><given-names>Anna M.</given-names></name><name xml:lang="ru"><surname>Косырева</surname><given-names>Анна Михайловна</given-names></name><name xml:lang="zh"><surname>Kosyreva</surname><given-names>Anna M.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Biology), Assistant Professor</p></bio><bio xml:lang="ru"><p>д-р биол. наук, доцент</p></bio><bio xml:lang="zh"><p>Dr. Sci. (Biology), Assistant Professor</p></bio><email>kosyreva.a@list.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6498-5764</contrib-id><contrib-id contrib-id-type="spin">7919-8430</contrib-id><name-alternatives><name xml:lang="en"><surname>Fathudinov</surname><given-names>Timur Kh.</given-names></name><name xml:lang="ru"><surname>Фатхудинов</surname><given-names>Тимур Хайсамудинович</given-names></name><name xml:lang="zh"><surname>Fatkhudinov</surname><given-names>Timur Kh.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Medicine), Professor</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор</p></bio><bio xml:lang="zh"><p>Dr. Sci. (Medicine), Professor</p></bio><email>tfat@yandex.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/><xref ref-type="aff" rid="aff3"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Peoples' Friendship University of Russia</institution></aff><aff><institution xml:lang="ru">Российский университет дружбы народов им. П. Лумумбы</institution></aff><aff><institution xml:lang="zh">Peoples' Friendship University of Russia</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Research Center for Obstetrics, Gynecology and Perinatology</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова</institution></aff><aff><institution xml:lang="zh">Research Center for Obstetrics, Gynecology and Perinatology</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Petrovsky National Research Centre of Surgery</institution></aff><aff><institution xml:lang="ru">Российский научный центр хирургии им. акад. Б.В. Петровского</institution></aff><aff><institution xml:lang="zh">Petrovsky National Research Centre of Surgery</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2026-01-15" publication-format="electronic"><day>15</day><month>01</month><year>2026</year></pub-date><pub-date date-type="pub" iso-8601-date="2026-03-23" publication-format="electronic"><day>23</day><month>03</month><year>2026</year></pub-date><volume>164</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>221</fpage><lpage>234</lpage><history><date date-type="received" iso-8601-date="2025-05-31"><day>31</day><month>05</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-09-15"><day>15</day><month>09</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2026,</copyright-statement><copyright-year>2026</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/" start_date="2029-03-23"/><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://j-morphology.com/1026-3543/article/view/681777">https://j-morphology.com/1026-3543/article/view/681777</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND:</bold> Macrophages are key regulators of inflammation and tissue regeneration and represent a promising tool for cell therapy. In rats, functional differences between macrophages derived from red bone marrow and peripheral blood remain insufficiently studied, particularly in the context of wound healing, where L-arginine metabolism plays a critical role.</p> <p><bold>AIM: </bold>To compare the expression levels of regulatory and proinflammatory cytokine genes (<italic>interleukin-1β</italic>, <italic>-6</italic>, and <italic>-10</italic>) and genes encoding L-arginine–metabolizing enzymes (<italic>Arg1</italic> and <italic>NOS2</italic>) in macrophages derived from bone marrow monocyte precursors and peripheral blood monocytes, and to assess their effects on cutaneous wound healing.</p> <p><bold>METHODS:</bold> Macrophages were generated from red bone marrow monocyte precursors and peripheral blood monocytes of Sprague–Dawley rats using recombinant macrophage colony-stimulating factor (rM-CSF). Macrophage phenotype was established using immunocytochemistry (staining for CD68 and CD43 markers). Gene expression levels were determined by real-time polymerase chain reaction and normalized to β2-microglobulin (<italic>β2M</italic>). The effects of macrophages on cutaneous wound healing were evaluated <italic>in vivo</italic>. Statistical analysis was performed using the Mann–Whitney <italic>U</italic> test (<italic>p</italic> &lt; 0.05).</p> <p><bold>RESULTS: </bold>Macrophages from both sources expressed CD68 and CD43. Red bone marrow (RBM)–derived macrophages demonstrated higher expression levels of <italic>IL-6</italic> and <italic>IL-10</italic> genes (<italic>p</italic> = 0.029 and <italic>p</italic> = 0.027, respectively), whereas peripheral blood (PB)–derived MPs showed higher expression of <italic>Arg1</italic> and <italic>NOS2</italic> (<italic>p</italic> = 0.029 for both genes). Administration of PB-derived macrophages did not result in complications, whereas RBM-derived macrophages were associated with wound bleeding. No accelerated wound healing was observed in either group.</p> <p><bold>CONCLUSION:</bold> RBM-derived macrophages exhibit enhanced activation potential, whereas PB-derived macrophages demonstrate a more pronounced influence on tissue regeneration. For cell-based therapy, PB-derived macrophages appear preferable due to a lower risk of complications. These findings highlight the importance of further investigation into the source-dependent activity of macrophages in reparative processes.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Обоснование.</bold> Макрофаги — ключевые регуляторы воспаления и регенерации, представляющие интерес для клеточной терапии. У крыс особенности функциональной активности макрофагов (МФ), зависящие от их происхождения — из красного костного мозга (ККМ) или периферической крови (ПК), — остаются малоизученными, особенно в контексте заживления ран, где важную роль играет превращение аминокислоты L-аргинина.</p> <p><bold>Цель исследования </bold>— сравнить уровни экспрессии генов регуляторных и провоспалительных цитокинов (<italic>IL-1β</italic>, <italic>IL-6</italic>, <italic>IL-10</italic>) и генов ферментов превращения аминокислоты L-аргинина (<italic>Arg1</italic> и <italic>NOS2</italic>) в макрофагах, полученных из моноцитарных предшественников красного костного мозга и из моноцитов периферической крови, а также оценить их влияние на заживление ран кожи.</p> <p><bold>Методы. </bold>Получение МФ из моноцитарных предшественников ККМ и моноцитов ПК крыс линии Sprague-Dawley с использованием rM-CSF (recombinant Macrophage Colony-Stimulating Factor). Иммуноцитохимическая оценка фенотипа МФ (окрашивание на маркеры CD68 и CD43). Определение уровней экспрессии генов методом ПЦР в реальном времени и нормализация относительно гена β2-микроглобулина (<italic>β2M</italic>). Изучение влияния макрофагов на заживление ран кожи <italic>in vivo</italic>. Статистический анализ с использованием критерия Манна–Уитни (<italic>p</italic> &lt; 0,05).</p> <p><bold>Результаты.</bold> МФ из обоих источников экспрессировали маркеры CD68 и CD43. В МФ-ККМ выявлен высокий уровень экспрессии генов <italic>IL-6</italic> и <italic>IL-10</italic> (<italic>p</italic> = 0,029, <italic>p</italic> = 0,027 соответственно); в МФ-ПК — высокий уровень экспрессии генов <italic>Arg1</italic> и <italic>NOS2</italic> (<italic>p</italic> = 0,029 для обоих генов). Введение МФ-ПК не вызывало осложнений, тогда как введение МФ-ККМ сопровождалось кровоточивостью ран. Ускорения темпов заживления ран не наблюдали.</p> <p><bold>Заключение. </bold>МФ-ККМ характеризуются повышенной способностью к активации, тогда как МФ-ПК оказывают выраженное влияние на регенерацию тканей. Для клеточной терапии предпочтительным является использование МФ-ПК ввиду меньшего риска развития осложнений. Полученные данные подчёркивают важность дальнейшего изучения зависимости активности макрофагов в репаративных процессах от источника их получения.</p></trans-abstract><trans-abstract xml:lang="zh"><p><bold>论证。</bold>巨噬细胞是炎症和再生过程中的关键调节因子，因此在细胞治疗领域备受关注。在大鼠中，巨噬细胞 (MF) 的功能活性取决于其来源 — — 红骨髓 (BM) 或外周血 (PB) — — 仍知之甚少，尤其是在伤口愈合方面，氨基酸 L-精氨酸的转化在其中发挥着重要作用。</p> <p><bold>目的。</bold>本研究旨在比较源自红骨髓单核细胞前体和外周血单核细胞的巨噬细胞中编码调节性和促炎细胞因子（IL-1β、IL-6、IL-10）的基因以及编码氨基酸 L-精氨酸转化酶（Arg1 和 NOS2）的基因的表达水平，并评估它们对皮肤伤口愈合的影响。</p> <p><bold>方法。</bold>使用重组巨噬细胞集落刺激因子（rM-CSF）从 Sprague-Dawley 大鼠的红骨髓单核细胞前体及外周血单核细胞中获取巨噬细胞。采用免疫细胞化学方法评估巨噬细胞的表型（CD68 和 CD43 标记染色）。通过实时 PCR 测定基因表达水平，并以 β2-微球蛋白（β2M）基因进行标准化。研究巨噬细胞对体内皮肤伤口愈合的影响。采用 Mann-Whitney 检验进行统计分析（p &lt; 0.05）。</p> <p><bold>结果。</bold>两种来源的巨噬细胞均表达CD68和CD43标记。在红骨髓来源的巨噬细胞（BM-Mφ）中，IL-6 和 IL-10 基因表达水平较高（p = 0.029；p = 0.027）；在外周血来源的巨噬细胞（PB-MF）中，Arg1 和 NOS2 基因表达水平较高（两个基因的 p = 0.029）。外周血来源巨噬细胞（PB-MF）的移植未引起并发症，而红骨髓来源巨噬细胞（BM-MF）的移植则伴有伤口出血。未观察到伤口愈合加速。</p> <p><bold>结论。</bold>红骨髓来源巨噬细胞（BM-MF）具有更强的活化潜能，而外周血来源巨噬细胞（PB-Mφ）则 对组织再生有显著影响。由于并发症风险较低，PB-MF 更适用于细胞治疗。所得数据强调了进一步研究巨噬细胞活性在修复过程中对其来源依赖性的重要性。</p></trans-abstract><kwd-group xml:lang="en"><kwd>macrophages</kwd><kwd>real-time PCR</kwd><kwd>wound model</kwd><kwd>L-arginine</kwd><kwd>cell therapy</kwd><kwd>cytokines</kwd><kwd>macrophage polarization</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>макрофаги</kwd><kwd>ПЦР в реальном времени</kwd><kwd>модель раны</kwd><kwd>L-аргинин</kwd><kwd>клеточная терапия</kwd><kwd>цитокины</kwd><kwd>поляризация макрофагов</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>巨噬细胞</kwd><kwd>实时 PCR</kwd><kwd>伤口模型</kwd><kwd>L-精氨酸</kwd><kwd>细胞治疗</kwd><kwd>细胞因子</kwd><kwd>巨噬细胞极化</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Российский научный фонд</institution></institution-wrap><institution-wrap><institution xml:lang="en">Russian Science Foundation</institution></institution-wrap><institution-wrap><institution xml:lang="zh">Russian Science Foundation</institution></institution-wrap></funding-source><award-id>24-25-00203</award-id></award-group><funding-statement xml:lang="en">The study was supported by the Russian Science Foundation (Grant No. 24-25-00203)</funding-statement><funding-statement xml:lang="ru">Работа поддержана Российским научным фондом (номер гранта 24-25-00203)</funding-statement><funding-statement xml:lang="zh">The study was supported by the Russian Science Foundation (Grant No. 24-25-00203)</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Kosyreva A, Dzhalilova D, Lokhonina A, et al. 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