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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">N.N. Priorov Journal of Traumatology and Orthopedics</journal-id><journal-title-group><journal-title xml:lang="en">N.N. Priorov Journal of Traumatology and Orthopedics</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник травматологии и ортопедии им. Н.Н. Приорова</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0869-8678</issn><issn publication-format="electronic">2658-6738</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">642053</article-id><article-id pub-id-type="doi">10.17816/vto642053</article-id><article-id pub-id-type="edn">FWNXPK</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>SCIENTIFIC REVIEWS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Научные 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">Prospects for using orthobiologic products in knee osteoarthritis: а review</article-title><trans-title-group xml:lang="ru"><trans-title>Перспективы применения ортобиологических препаратов при остеоартрите коленного сустава: обзор</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4598-1194</contrib-id><contrib-id contrib-id-type="spin">1771-4358</contrib-id><name-alternatives><name xml:lang="en"><surname>Ustyugov</surname><given-names>Andrey Yu.</given-names></name><name xml:lang="ru"><surname>Устюгов</surname><given-names>Андрей Юрьевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>Leikos@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/0000-0002-2789-6172</contrib-id><contrib-id contrib-id-type="spin">8749-3890</contrib-id><name-alternatives><name xml:lang="en"><surname>Torgashin</surname><given-names>Alexander N.</given-names></name><name xml:lang="ru"><surname>Торгашин</surname><given-names>Александр Николаевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>alexander.torgashin@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5016-3201</contrib-id><contrib-id contrib-id-type="spin">4725-3840</contrib-id><name-alternatives><name xml:lang="en"><surname>Zorina</surname><given-names>Alla  I.</given-names></name><name xml:lang="ru"><surname>Зорина</surname><given-names>Алла Ивановна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><email>doc_zorin@inbox.ru</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9481-4061</contrib-id><contrib-id contrib-id-type="spin">1785-7652</contrib-id><name-alternatives><name xml:lang="en"><surname>Zorin</surname><given-names>Vadim L.</given-names></name><name xml:lang="ru"><surname>Зорин</surname><given-names>Вадим Леонидович</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><email>doc_zorin@inbox.ru</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2078-4274</contrib-id><contrib-id contrib-id-type="spin">2339-5729</contrib-id><name-alternatives><name xml:lang="en"><surname>Kopnin</surname><given-names>Pavel B.</given-names></name><name xml:lang="ru"><surname>Копнин</surname><given-names>Павел Борисович</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><email>pbkopnin@mail.ru</email><xref ref-type="aff" rid="aff4"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Priorov National Medical Research Center of Traumatology and Orthopedics</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр травматологии и ортопедии им. Н.Н. Приорова</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Pirogov Russian National Research Medical University</institution></aff><aff><institution xml:lang="ru">Российский национальный исследовательский медицинский университет им. Н.И. Пирогова</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Artgen Biotech, Skincel (Skolkovo)</institution></aff><aff><institution xml:lang="ru">ПАО «Артген биотех», ООО «Скинцел» (Сколково)</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">Blokhin National Medical Research Center of Oncology</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-12-21" publication-format="electronic"><day>21</day><month>12</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2026-04-02" publication-format="electronic"><day>02</day><month>04</month><year>2026</year></pub-date><volume>33</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>220</fpage><lpage>239</lpage><history><date date-type="received" iso-8601-date="2024-11-19"><day>19</day><month>11</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2025-09-03"><day>03</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-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="2027-04-02"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://eco-vector.com/for_authors.php#07</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.eco-vector.com/0869-8678/article/view/642053">https://journals.eco-vector.com/0869-8678/article/view/642053</self-uri><abstract xml:lang="en"><p>Osteoarthritis is the most common joint disease, causing damage to cartilage and surrounding tissues and potentially leading to varying degrees of disability. The disease is characterized by pain, stiffness, and loss of function. Osteoarthritis is classified as primary and secondary. The cause of primary (or idiopathic) osteoarthritis is unknown (primary osteoarthritis accounts for the vast majority of cases). Secondary osteoarthritis may be caused by another disease or disorder, such as infection, congenital joint malformation, trauma, metabolic disorders, rheumatoid arthritis, and others. The main goals of treatment include relief of pain, preservation of joint flexibility, and optimization of joint function. Currently used conservative treatment methods are mainly aimed at reducing pain and improving the patient’s quality of life; however, they do not eliminate the underlying cause of the disease and, accordingly, are not capable of completely halting the degradation of hyaline cartilage. Attempts at joint-preserving surgery in cases of involvement of one of the knee joint compartments, such as corrective osteotomy, can significantly improve treatment outcomes but tend to delay rather than prevent the need for joint arthroplasty. Therefore, the development of treatment methods that enable joint preservation and restoration of cartilage and subchondral bone defects remains highly relevant. At present, the search for such methods is focused on the use of orthobiologic products. This article addresses the application of these approaches in the treatment of knee joint conditions. A detailed description of the composition and mechanisms of action of two orthobiologic products of greatest interest to practicing clinicians—platelet-rich plasma and stromal vascular fraction—is presented. The results of preclinical and clinical studies demonstrating the ability of these products to reduce inflammation, alleviate pain, and remarkably improve the function of the affected joint are provided. Thus, scientific studies confirm the therapeutic efficacy of orthobiologic products, the use of which opens new prospects for joint-preserving treatment of patients with osteoarthritis.</p></abstract><trans-abstract xml:lang="ru"><p>Остеоартрит — наиболее распространённое заболевание суставов, вызывающее повреждение хрящей и окружающих их тканей и способное привести к инвалидности различной степени. Для заболевания характерны боль, скованность и утрата функции. Остеоартрит подразделяют на первичный и вторичный. Причина возникновения первичного (или идиопатического) остеоартрита неизвестна (первичный остеоартрит представляет подавляющее большинство случаев этого заболевания). Вторичный остеоартрит может быть вызван другим заболеванием или нарушением, таким как инфекция, врождённый порок развития сустава, травма, нарушение обмена веществ, ревматоидный артрит и т.п. К основным задачам лечения относятся купирование болевого синдрома, сохранение гибкости сустава, оптимизация его функций. Применяемые сегодня консервативные методы лечения направлены главным образом на снижение боли, улучшение качества жизни пациента, однако не устраняют основную причину заболевания и, соответственно, не способны полностью остановить деградацию гиалинового хряща. Попытки выполнения органосохраняющих операций при поражении одного из компартментов коленного сустава, таких как корригирующая остеотомия, позволяют значительно улучшить результаты лечения, но дают возможность лишь отсрочить эндопротезирование сустава, а не избежать его. В связи с этим разработка методов лечения, позволяющих сохранить сустав, восполнить дефекты хряща и субхондральной кости, остаётся весьма актуальной. Сегодня в поисках таких методов акцент делают на использовании ортобиологических продуктов. В статье рассматриваются вопросы применения данных методик в лечении патологий коленного сустава. Представлено подробное описание состава и механизмов действия двух ортобиологических продуктов, вызывающих наибольший интерес у практикующих специалистов, — плазмы, обогащённой тромбоцитами, и стромально-васкулярной фракции. Приведены результаты доклинических и клинических исследований, доказывающие способность этих продуктов устранять воспаление, снижать болевой синдром и значительно улучшать функцию поражённого сустава. Таким образом, в научных исследованиях подтверждена терапевтическая эффективность ортобиологических продуктов, применение которых открывает новые перспективы в органосохраняющем лечении пациентов, страдающих остеоартритом.</p></trans-abstract><kwd-group xml:lang="en"><kwd>orthobiologic products</kwd><kwd>platelet-rich plasma</kwd><kwd>stromal vascular fraction</kwd><kwd>osteoarthritis</kwd><kwd>knee osteoarthritis</kwd><kwd>joint-preserving treatment of osteoarthritis</kwd><kwd>review</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>ортобиологические продукты</kwd><kwd>плазма, обогащённая тромбоцитами</kwd><kwd>стромально-васкулярная фракция</kwd><kwd>остеоартрит</kwd><kwd>остеоартрит коленного сустава</kwd><kwd>органосохраняющее лечение остеоартрита</kwd><kwd>обзор</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Findlay DM. If good things come from above, do bad things come from below? Arthritis Res Ther. 2010;12(3):119. doi: 10.1186/ar3007</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Hunter DJ, March L, Chew M. Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet. 2020;396(10264):1711–1712. doi: 10.1016/S0140-6736(20)32230-3</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Martel-Pelletier J, Barr AJ, Cicuttini FM, et al. Osteoarthritis. Nat Rev Dis Primers. 2016;2:16072. doi: 10.1038/nrdp.2016.72</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Toh WS, Brittberg M, Farr J, et al. Cellular senescence in aging and osteoarthritis: implications for cartilage repair. Acta Orthop. 2016;87(Suppl 1):6–14. doi: 10.1080/17453674.2016.1235087</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Haslauer CM, Elsaid KA, Fleming BC, et al. Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury. Osteoarthritis Cartilage. 2013;21(12):1950–1957. doi: 10.1016/j.joca.2013.09.003</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Wilson JF. To stop osteoarthritis, fixing cartilage may not be enough. Ann Intern Med. 2007;147(6):437–439. doi: 10.7326/0003-4819-147-6-200709180-0002</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182): 1745–1759. doi: 10.1016/S0140-6736(19)30417-9</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Mora JC, Przkora R, Cruz-Almeida Y. Knee osteoarthritis: pathophysiology and current treatment modalities. J Pain Res. 2018;11:2189–2196. doi: 10.2147/JPR.S154002</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Niinimäki TT, Eskelinen A, Mann BS, et al. Survivorship of high tibial osteotomy in the treatment of osteoarthritis of the knee: Finnish registry-based study of 3195 knees. J Bone Joint Surg Br. 2012;94(11):1517–1521. doi: 10.1302/0301-620X.94B11.29601</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Khoshbin A, Sheth U, Ogilvie-Harris D, et al. The effect of patient, provider and surgical factors on survivorship of high tibial osteotomy to total knee arthroplasty: a population-based study. Knee Surg Sports Traumatol Arthrosc. 2017;25(3):887–894. doi: 10.1007/s00167-015-3849-4</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Filardo G, Perdisa F, Roffi A, Marcacci M. Stem cells in articular cartilage regeneration. J Orthop Surg Res. 2016;11:42. doi: 10.1186/s13018-016-0378-x</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Betzler BK, Chew AH, Razak HR. Intra-articular injection of orthobiologics in patients undergoing high tibial osteotomy for knee osteoarthritis is safe and effective — a systematic review. J Exp Orthop. 2021;8(1):83. doi: 10.1186/s40634-021-00387-2</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Primorac D, Molnar V, Rod E, et al. Knee Osteoarthritis: A Review of Pathogenesis and State-of-the-Art Non-Operative Therapeutic Considerations. Genes (Basel). 2020;11(8):854. doi: 10.3390/genes11080854</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Chahla J, Mandelbaum BR. Biological treatment for osteoarthritis of the knee: moving from bench to bedside—current practical concepts. Arthroscopy. 2018;34(5):1719–1729. doi: 10.1016/j.arthro.2018.01.048</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Andia I, Maffulli N. New biotechnologies for musculoskeletal injuries. Surgeon. 2019;17(4):244–255. doi: 10.1016/j.surge.2018.08.004</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Zlotnicki JP, Geeslin AG, Murray IR, et al. Biologic treatments for sports injuries II think tank — current concepts, future research, and barriers to advancement, part 3: articular cartilage. Orthop J Sports Med. 2016;4(4):2325967116642433. doi: 10.1177/2325967116642433</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not ostearthrosis!). Osteoarthritis Cartilage. 2013;21(1):16–21. doi: 10.1016/j.joca.2012.11.012</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014;2014:561459. doi: 10.1155/2014/561459</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis. 2013;5(2):77–94. doi: 10.1177/1759720X12467868</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51(2):249–257. doi: 10.1016/j.bone.2012.02.012</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Larsson S, Englund M, Struglics A, Lohmander LS. Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy. Osteoarthritis Cartilage. 2015;23(11):1906–1914. doi: 10.1016/j.joca.2015.05.035</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Ude CC, Shah S, Ogueri KS, et al. Stromal Vascular Fraction for Osteoarthritis of the Knee Regenerative Engineering. Regen Eng Transl Med. 2022;8(2):210–224. doi: 10.1007/s40883-021-00226-x</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Dayer JM. The process of identifying and understanding cytokines: from basic studies to treating rheumatic diseases. Best Pract Res Clin Rheumatol. 2004;18(1):31–45. doi: 10.1016/j.berh.2003.09.009</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33–42. doi: 10.1038/nrrheum.2010.196</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage. 2012;20(12):1484–1499. doi: 10.1016/j.joca.2012.08.027</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Marx RE. Platelet rich plasma (PRP): What is PRP and what is not PRP? Implant Dent. 2001;10(4):225–228. doi: 10.1097/00008505-200110000-00002</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Arshdeep, Kumaran DM. Platelet-rich plasma in dermatology: Boon or a bane? Indian J Dermatol Venereol Leprol. 2014;80(1):5–14. doi: 10.4103/0378-6323.125467</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Alcaraz MJ, Compañ A, Guillén MI. Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases. Cells. 2020;9(1):98. doi: 10.3390/cells9010098</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Sommeling C, Heyneman A, Hoeksema H, et al. The use of platelet-rich plasma in plastic surgery: a systematic review. J Plast Reconstr Aesthet Surg. 2013;66(3):301–312. doi: 10.1016/j.bjps.2012.11.009</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62(4):489–496. doi: 10.1016/j.joms.2003.12.003</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Kang YH, Jeon SH, Park JY, et al. Platelet-rich fibrin is a bioscaffold and reservoir of growth factors for tissue regeneration. Tissue Eng Part A. 2011;17(3-4):349–359. doi: 10.1089/ten.TEA.2010.0327</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Kim DH, Je YJ, Kim CD, et al. Can platelet-rich plasma be used for skin rejuvenation? Evaluation of effects of platelet-rich plasma on human dermal fibroblast. Ann Dermatol. 2011;23(4):424–431. doi: 10.5021/ad.2011.23.4.424</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Senzel L, Gnatenko DV, Bahou WF. The platelet proteome. Curr Opin Hematol. 2009;16(5):329–333. doi: 10.1097/MOH.0b013e32832e9dc6</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Fortier LA, Barker JU, Strauss EJ, et al. The role of growth factors in cartilage repair. Clin Orthop Relat Res. 2011;469(10):2706–2715. doi: 10.1007/s11999-011-1857-3</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Nurden AT, Nurden P, Sanchez M, et al. Platelets and wound healing. Front Biosci. 2008;13:3532–3548. doi: 10.2741/2947</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Qureshi AH, Chaoji V, Maiguel D, et al. Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. PLoS One. 2009;4(10):e7627. doi: 10.1371/journal.pone.0007627</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Akeda K, An HS, Okuma M, et al. Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthritis Cartilage. 2006;14(12):1272–1280. doi: 10.1016/j.joca.2006.05.008</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Mishra A, Tummala P, King A, et al. Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng Part C Methods. 2009;15(3):431–435. doi: 10.1089/ten.tec.2008.0534</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Anitua E, Sanchez M, Nurden AT, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford). 2007;46(12):1769–1772. doi: 10.1093/rheumatology/kem234</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013;9(12):721–730. doi: 10.1038/nrrheum.2013.141</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(6):2135–2140. doi: 10.1177/0363546511417792</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Woodell-May J, Matuska A, Oyster M, et al. Autologous protein solution inhibits MMP-13 production by IL-1beta and TNFalpha-stimulated human articular chondrocytes. J Orthop Res. 2011;29(6):1320–1326. doi: 10.1002/jor.21384</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Xie X, Zhang C, Tuan R. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther. 2014;16(1):204. doi: 10.1186/ar4493</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Malemud CJ. Anticytokine therapy for osteoarthritis: evidence to date. Drugs Aging. 2010;27(2):95–115. doi: 10.2165/11319950-000000000-00000</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Moller B, Paulukat J, Nold M, et al. Interferon-gamma induces expression of interleukin-18 binding protein in fibroblast-like synoviocytes. Rheumatology (Oxford). 2003;42(3):442–445. doi: 10.1093/rheumatology/keg146</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Wu CC, Chen WH, Zao B, et al. Regenerative potentials of platelet-rich plasma enhanced by collagen in retrieving pro-inflammatory cytokine-inhibited chondrogenesis. Biomaterials. 2011;32(25):5847–5854. doi: 10.1016/j.biomaterials.2011.05.002</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Meheux CJ, McCulloch PC, Lintner DM, et al. Efficacy of Intra–articular Platelet–Rich Plasma Injections in Knee Osteoarthritis: A systematic review. Arthroscopy. 2016;32(3):495–505. doi: 10.1016/j.arthro.2015.08.005</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Iwanaga T, Shikichi M, Kitamura H, et al. Morphology and functional roles of synoviocytes in the joint. Arch Histol Cytol. 2000;63(1):17–31. doi: 10.1679/aohc.63.17</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Bannuru RR, Natov NS, Dasi UR, et al. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis — meta-analysis. Osteoarthritis Cartilage. 2011;19(6):611–619. doi: 10.1016/j.joca.2010.09.014</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Nagata MJ, Messora MR, Furlaneto FA, et al. Effectiveness of two methods for preparation of autologous platelet-rich plasma: an experimental study in rabbits. Eur J Dent. 2010;4(3):395–402.</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Bendinelli P, Matteucci E, Dogliotti G, et al. Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-kB inhibition via HGF. J Cell Physiol. 2010;225:757–766. doi: 10.1002/jcp.22274</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Cole BJ, Karas V, Hussey K, et al. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017;45(2):339–346. doi: 10.1177/0363546516665809</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Dai WL, Zhou AG, Zhang H, et al. Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Arthroscopy. 2017;33:659–670.e1</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Shen L, Yuan T, Chen S. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017;12(1):16. doi: 10.1186/s13018-017-0521-3</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Filardo G, Kon E, Pereira Ruiz MT, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20:2082–2091. doi: 10.1007/s00167-011-1837-x</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Sánchez M, Anitua E, Azofra J, et al. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol. 2008;26(5):910–913.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Kon E, Buda R, Filardo G, et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010;18:472–479. doi: 10.1007/s00167-009-0940-8</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Lippross S, Moeller B, Haas H, et al. Intraarticular injection of platelet-rich plasma reduces inflammation in a pig model of rheumatoid arthritis of the knee joint. Arthritis Rheum. 2011;63(11):3344–3353. doi: 10.1002/art.30547</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>van den Berg WB. Osteoarthritis year 2010 in review: pathomechanisms. Osteoarthritis Cartilage. 2011;19:338–341. doi: 10.1016/j.joca.2011.01.022</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Browning SR, Weiser AM, Woolf N, et al. Platelet-rich plasma increases matrix metalloproteinases in cultures of human synovial fibroblasts. J Bone Joint Surg Am. 2012;94:1721–1727. doi: 10.2106/JBJS.K.01501</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Bernstein J. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. J Bone Joint Surg Am. 2004;86-A(11):2567. doi: 10.2106/00004623-200411000-00032</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Laudy AB, Bakker EW, Rekers M, et al. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49:657–72. doi: 10.1136/bjsports-2015-095503</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Sadabad HN, Behzadifar M, Arasteh F, et al. Efficacy of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: a systematic review and meta-analysis. Electron Physician. 2016;8:2115–22. doi: 10.19082/2115</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Chang KV, Hung CY, Aliwarga F, et al. Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014;95:562–575. doi: 10.1016/j.apmr.2013.11.006</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Xu Z, Luo J, Huang X, et al. Efficacy of platelet-rich plasma in pain and self-report function in knee osteoarthritis: a best-evidence synthesis. Am J Phys Med Rehabil. 2017;96:793–800. doi: 10.1097/PHM.0000000000000746</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Zhang HF, Wang CG, Li H, et al. Intra-articular platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis. Drug Des Devel Ther. 2018;12:445–453. doi: 10.2147/DDDT.S171019</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Ehrenfest DMD, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol. 2009;27:158–167. doi: 10.1016/j.tibtech.2009.06.003</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Nie LY, Zhao K, Ruan J, et al. Effectiveness of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. A Meta-analysis of Randomized Controlled Clinical Trials. Orthop J Sports Med. 2021;9(3):2325967120973284. doi: 10.1177/2325967120973284</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Dragoo JL, Braun HJ, Durham JL, et al. Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons. Am J Sports Med. 2012;40:1274–1281. doi: 10.1177/0363546512442411</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Nakajima R, Saita Y, Kobayashi Y, et al. Comparison of bioactive substances in novel-developed freeze-dried platelet-rich plasma (PRP) and activated normal PRP, and investigation of bioactive substance levels after long-term storage. Regenerative Therapy. 2024;27:200–206. doi: 10.1016/j.reth.2023.102120</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Xie X, Wang Y, Zhao C, et al. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials. 2012;33:7008–7018. doi: 10.1016/j.biomaterials.2012.06.058</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Bora P, Majumdar S. Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem Cell Res Ther. 2017;8:145. doi: 10.1186/s13287-017-0598-y</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Pers YM, Rackwitz L, Ferreira R, et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med. 2016;5(7):847–856.</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture-expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15:641–648. doi: 10.1016/j.jcyt.2013.02.006</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Lana J, Lana A, da Fonseca LF, et al. Stromal Vascular Fraction for Knee Osteoarthritis — An Update. JSRM. 2022;18(1):11–20. doi: 10.46582/jsrm.1801003</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Hofer HR, Tuan RS. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther. 2016;7:131. doi: 10.1186/s13287-016-0394-0</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–150. doi: 10.1016/j.stem.2007.11.014</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Tremolada C, Colombo V, Ventura C. Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development. Curr Stem Cell Rep. 2016;2(3):304–312. doi: 10.1007/s40778-016-0053-5</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Han S, Sun HM, Hwang KC, et al. Adipose-Derived Stromal Vascular Fraction Cells: Update on Clinical Utility and Efficacy. Crit Rev Eukaryot Gene Expr. 2015;25(2):145–52. doi: 10.1016/j.stem.2007.11.014</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>DiMarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013;4:20. doi: 10.3389/fimmu.2013.00201</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Michalek J, Vrablikova A, Darinskas A, et al. Stromal vascular fraction cell therapy for osteoarthritis in elderly: Multicenter case-control study. J Clin Orthop Trauma. 2019;10(1):76–80. doi: 10.1016/j.jcot.2018.11.010</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Tsubosaka M, Matsumoto T, Sobajima S, et al. The influence of adipose-derived stromal vascular fraction cells on the treatment of knee osteoarthritis. BMC Musculoskelet Disord. 2020;21(1):207. doi: 10.1186/s12891-020-03234-6</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Lapuente JP, Dos-Anjos S, Blázquez-Martínez A. Intraarticular infiltration of adipose-derived stromal vascular fraction cells slows the clinical progression of moderate-severe knee osteoarthritis: hypothesis on the regulatory role of intra-articular adipose tissue. J Orthop Surg Res. 2020;15(1):137. doi: 10.1186/s13018-020-01715-6</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>Simunec D, Salari H, Meyer J. Treatment of Grade 3 and 4 Osteoarthritis Intraoperatively Separated Adipose Tissue-Derived Stromal Vascular Fraction: A Comparative Case Series. Cells. 2020;9(9):2096. doi: 10.3390/cells9092096</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Ude CC, Shah S, Ogueri KS, et al. Stromal Vascular Fraction for Osteoarthritis of the Knee. Regen Eng Transl Med. 2021;8(2):210–224. doi: 10.1007/s40883-021-00226-x</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Alcaraz M, Compañ A, Guillén M. Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases. Cells. 2020;9(1):98. doi: 10.3390/cells9010098</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>Manferdini C, Maumus M, Gabusi E, et al. Adipose-derived mesenchymal stem cells exert anti-inflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis Rheum. 2013;65:1271–1281. doi: 10.1002/art.37864</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>Song WJ, Li Q, Ryu MO, et al. TSG-6 secreted by human adipose tissue-derived mesenchymal stem cells ameliorates DSS-induced colitis by inducing M2 macrophage polarization in mice. Sci Rep. 2017;7:5187. doi: 10.1038/s41598-017-05427-8</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Ortiz-Virumbrales M, Menta R, Pérez LM, et al. Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2. Stem Cell Res Ther. 2020;11:462. doi: 10.1186/s13287-020-01924-3</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Filardo G, Tschon M, Perdisa F, et al. Micro-fragmentation is a valid alternative to cell expansion and enzymatic digestion of adipose tissue for the treatment of knee osteoarthritis: a comparative preclinical study. Knee Surg Sports Traumatol Arthrosc. 2021;30(3):773–781. doi: 10.1007/s00167-021-06534-5</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>Tofiño-Vian M, Guillén MI, del Caz MD, et al. Extracellular vesicles from adipose-derived mesenchymal stem cells downregulate senescence features in osteoarthritic osteoblasts. Oxid Med Cell Longev. 2017;2017:7197598. doi: 10.1155/2017/7197598</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317. doi: 10.1080/14653240600855905</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>Maumus M, Peyrafitte JA, D’Angelo R, et al. Native human adipose stromal cells: localization, morphology and phenotype. Int J Obes (Lond). 2011;35(9):1141–1153. doi: 10.1038/ijo.2010.269</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>ter Huurne M, Schelbergen R, Blattes R, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012;64(11):3604–3613. doi: 10.1002/art.34626</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>Desando G, Cavallo C, Sartoni F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 2013;15(1):R22. doi: 10.1186/ar4156</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>Orfei CP, Boffa A, Sourugeon Y, et al. Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies. Knee Surg Sports Traumatol Arthrosc. 2023;31(2):641–655. doi: 10.1007/s00167-022-07063-7</mixed-citation></ref><ref id="B97"><label>97.</label><mixed-citation>Kamada K, Matsushita T, Yamashita T, et al. Attenuation of knee osteoarthritis progression in mice through polarization of M2 macrophages by intra-articular transplantation of non-cultured human adipose-derived regenerative cells. J Clin Med. 2021;10(18):4309. doi: 10.3390/jcm10194309</mixed-citation></ref><ref id="B98"><label>98.</label><mixed-citation>Si Z, Wang X, Sun C, et al. Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies. Biomed Pharmacother. 2019;114:108765. doi: 10.1016/j.biopha.2019.108765</mixed-citation></ref><ref id="B99"><label>99.</label><mixed-citation>Freitag J, Bates D, Wickham J, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14(3):213–230. doi: 10.2217/rme-2018-0161</mixed-citation></ref><ref id="B100"><label>100.</label><mixed-citation>Roato I, Belisario DC, Compagno M, et al. Concentrated adipose tissue infusion for the treatment of knee osteoarthritis: clinical and histological observations. Int Orthop. 2019;43(1):15–23. doi: 10.1007/s00264-018-4192-4</mixed-citation></ref><ref id="B101"><label>101.</label><mixed-citation>Panni AS, Vasso M, Braile A, et al. Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response. Int Orthop. 2019;43(1):7–13. doi: 10.1007/s00264-018-4182-6</mixed-citation></ref><ref id="B102"><label>102.</label><mixed-citation>Nakamura N, Yokota N, Hattori M, et al. Comparative Clinical Outcomes After Intra-articular Injection with Adipose-Derived Cultured Stem Cells or Noncultured Stromal Vascular Fraction for the Treatment of Knee Osteoarthritis: Response. Am J Sports Med. 2020;48(1):NP19–NP20. doi: 10.1177/0363546519895242</mixed-citation></ref><ref id="B103"><label>103.</label><mixed-citation>Spasovski D, Spasovski V, Baščarević Z, et al. Intra-articular injection of autologous adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis. J Gene Med. 2018;20(1):e3002. doi: 10.1002/jgm.3002</mixed-citation></ref><ref id="B104"><label>104.</label><mixed-citation>Song Y, Du H, Dai C, et al. Human adipose-derived mesenchymal stem cells for osteoarthritis: a pilot study with long-term follow-up and repeated injections. Regen Med. 2018;13(3):295–307. doi: 10.2217/rme-2017-0152</mixed-citation></ref><ref id="B105"><label>105.</label><mixed-citation>Delco ML, Goodale M, Talts JF, et al. Integrin α10β1-selected mesenchymal stem cells mitigate the progression of osteoarthritis in an equine talar impact model. Am J Sports Med. 2020;48(3):612–623. doi: 10.1177/0363546519899087</mixed-citation></ref><ref id="B106"><label>106.</label><mixed-citation>Pleumeekers MM, Nimeskern L, Koevoet JLM, et al. Trophic effects of adipose-tissue-derived and bone-marrow-derived mesenchymal stem cells enhance cartilage generation by chondrocytes in co-culture. PLoS One. 2018;13(2):e0190744. doi: 10.1371/journal.pone.0190744</mixed-citation></ref><ref id="B107"><label>107.</label><mixed-citation>Ahmad MR, Badar W, Ullah Khan MA, et al. Combination of preconditioned adipose-derived mesenchymal stem cells and platelet-rich plasma improves the repair of osteoarthritis in rat. Regen Med. 2020;15(12):2285–2295. doi: 10.2217/rme-2020-0040</mixed-citation></ref><ref id="B108"><label>108.</label><mixed-citation>Yun S, Ku SK, Kwon YS. Adipose-derived mesenchymal stem cells and platelet-rich plasma synergistically ameliorate the surgical-induced osteoarthritis in Beagle dogs. J Orthop Surg Res. 2016;11:9. doi: 10.1186/s13018-016-0342-9</mixed-citation></ref><ref id="B109"><label>109.</label><mixed-citation>Agarwal N, Mak C, Bojanic C, et al. Meta-analysis of adipose tissue derived cell-based therapy for the treatment of knee osteoarthritis. Cells. 2021;10(6):1365. doi: 10.3390/cells10061365</mixed-citation></ref><ref id="B110"><label>110.</label><mixed-citation>Jo CH, Chai JW, Jeong EC, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a 2-year follow-up study. Am J Sports Med. 2017;45(12):2774–2783. doi: 10.1177/0363546517716641</mixed-citation></ref><ref id="B111"><label>111.</label><mixed-citation>Qu H, Sun S. Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2021;16(1):11. doi: 10.1186/s13018-020-02151-1</mixed-citation></ref><ref id="B112"><label>112.</label><mixed-citation>Wang J, Zhou L, Zhang Y, et al. Mesenchymal stem cells — a promising strategy for treating knee osteoarthritis: a systematic review and meta-analysis. Bone Joint Res. 2020;9(10):719–728. doi: 10.1302/2046-3758.910.BJR-2020-0031.R3</mixed-citation></ref><ref id="B113"><label>113.</label><mixed-citation>Pers YM, Rackwitz L, Ferreira R, et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med. 2016;5(7):847–856. doi: 10.5966/sctm.2015-0245</mixed-citation></ref><ref id="B114"><label>114.</label><mixed-citation>You D, Jang MJ, Kim BH, et al. Comparative study of autologous stromal vascular fraction and adipose-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury. Stem Cells Transl Med. 2015;4(4):351–358. doi: 10.5966/sctm.2014-0161</mixed-citation></ref><ref id="B115"><label>115.</label><mixed-citation>Pak J, Chang JJ, Lee JH, et al. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord. 2013;14:337. doi: 10.1186/1471-2474-14-337</mixed-citation></ref><ref id="B116"><label>116.</label><mixed-citation>Matsumoto D, Sato K, Gonda K, et al. Cell-assisted lipotransfer: supportive use of human adipose-derived cells for soft tissue augmentation with lipoinjection. Tissue Eng. 2006;12(12):3375–3382. doi: 10.1089/ten.2006.12.3375</mixed-citation></ref><ref id="B117"><label>117.</label><mixed-citation>Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 2014;32(5):1254–1266. doi: 10.1002/stem.1634</mixed-citation></ref><ref id="B118"><label>118.</label><mixed-citation>Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211–228. doi: 10.1089/107632701300062859</mixed-citation></ref><ref id="B119"><label>119.</label><mixed-citation>Oberbauer E, Steffenhagen C, Wurzer C, et al. Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: current state of the art. Cell Regen. 2015;4:7. doi: 10.1186/s13619-015-0020-0</mixed-citation></ref><ref id="B120"><label>120.</label><mixed-citation>Aronowitz JA, Lockhart RA, Hakakian C. Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue. Springerplus. 2015;4:713. doi: 10.1186/s40064-015-1509-2</mixed-citation></ref><ref id="B121"><label>121.</label><mixed-citation>Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int. 2012;2012:812693. doi: 10.1155/2012/812693</mixed-citation></ref><ref id="B122"><label>122.</label><mixed-citation>Conde-Green A, Rodriguez RL, Slezak S, et al. Comparison between enzymatic digestion and mechanical processing of aspirated adipose tissue. Plast Reconstr Surg. 2014;134(4S-1):54. doi: 10.1097/01.prs.0000455394.06800.62</mixed-citation></ref><ref id="B123"><label>123.</label><mixed-citation>Blaber SP, Webster RA, Hill CJ, et al. Analysis of in vitro secretion profiles from adipose-derived cell populations. J Transl Med. 2012;10:172. doi: 10.1186/1479-5876-10-172</mixed-citation></ref><ref id="B124"><label>124.</label><mixed-citation>Chazenbalk G, Bertolotto C, Heneidi S, et al. Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity. PLoS One. 2011;6(3):e17834. doi: 10.1371/journal.pone.0017834</mixed-citation></ref><ref id="B125"><label>125.</label><mixed-citation>Hosseini S, Taghiyar L, Safari F, et al. Regenerative medicine applications of mesenchymal stem cells. Adv Exp Med Biol. 2018;1089:115–141. doi: 10.1007/5584_2018_213</mixed-citation></ref><ref id="B126"><label>126.</label><mixed-citation>Klar AS, Güven S, Biedermann T, et al. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells. Biomaterials. 2014;35(19):5065–5078. doi: 10.1016/j.biomaterials.2014.02.049</mixed-citation></ref><ref id="B127"><label>127.</label><mixed-citation>Traktuev DO, Prater DN, Merfeld-Clauss S, et al. Robust functional vascular network formation in vivo by cooperation of adipose progenitor and endothelial cells. Circ Res. 2009;104(12):1410–1420. doi: 10.1161/CIRCRESAHA.108.190926</mixed-citation></ref><ref id="B128"><label>128.</label><mixed-citation>Traktuev DO, Merfeld-Clauss S, Li J, et al. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. 2008;102(1):77–85. doi: 10.1161/CIRCRESAHA.107.159475</mixed-citation></ref><ref id="B129"><label>129.</label><mixed-citation>Koh YJ, Koh BI, Kim H, et al. Stromal vascular fraction from adipose tissue forms profound vascular network through the dynamic reassembly of blood endothelial cells. Arterioscler Thromb Vasc Biol. 2011;31(5):1141–1150. doi: 10.1161/ATVBAHA.110.218206</mixed-citation></ref><ref id="B130"><label>130.</label><mixed-citation>Kwon HM, Hur SM, Park KY, et al. Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis. Vascul Pharmacol. 2014;63(1):19–28. doi: 10.1016/j.vph.2014.06.004</mixed-citation></ref><ref id="B131"><label>131.</label><mixed-citation>Zhu M, Dong Z, Gao J, et al. Adipocyte regeneration after free fat transplantation: promotion by stromal vascular fraction cells. Cell Transplant. 2015;24(1):49–62. doi: 10.3727/096368913X675133</mixed-citation></ref><ref id="B132"><label>132.</label><mixed-citation>Premaratne GU, Ma LP, Fujita M, et al. Stromal vascular fraction transplantation as an alternative therapy for ischemic heart failure: anti-inflammatory role. J Cardiothorac Surg. 2011;6:43. doi: 10.1186/1749-8090-6-43</mixed-citation></ref><ref id="B133"><label>133.</label><mixed-citation>Alcaraz MJ, Compañ A, Guillén MI. Extracellular vesicles from mesenchymal stem cells as novel treatments for musculoskeletal diseases. Cells. 2020;9(1):98. doi: 10.3390/cells9010098</mixed-citation></ref><ref id="B134"><label>134.</label><mixed-citation>Eto H, Ishimine H, Kinoshita K, et al. Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency. Stem Cells Dev. 2013;22(6):985–997. doi: 10.1089/scd.2012.0442</mixed-citation></ref><ref id="B135"><label>135.</label><mixed-citation>Zeyda M, Farmer D, Todoric J, et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond). 2007;31(9):1420–1428. doi: 10.1038/sj.ijo.0803632</mixed-citation></ref><ref id="B136"><label>136.</label><mixed-citation>Tiemessen MM, Jagger AL, Evans HG, et al. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci U S A. 2007;104(49):19446–19451. doi: 10.1073/pnas.0706832104</mixed-citation></ref><ref id="B137"><label>137.</label><mixed-citation>Yu L, Yang F, Zhang F, et al. CD69 enhances immunosuppressive function of regulatory T-cells and attenuates colitis by prompting IL-10 production. Cell Death Dis. 2018;9(9):905. doi: 10.1038/s41419-018-0927-9</mixed-citation></ref><ref id="B138"><label>138.</label><mixed-citation>Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol. 2019;10:1191. doi: 10.3389/fimmu.2019.01191</mixed-citation></ref><ref id="B139"><label>139.</label><mixed-citation>Puissant B, Barreau C, Bourin P, et al. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol. 2005;129(1):118–129. doi: 10.1111/j.1365-2141.2005.05409.x</mixed-citation></ref><ref id="B140"><label>140.</label><mixed-citation>Kim SH, Ha CW, Park YB, et al. Intra-articular injection of mesenchymal stem cells for clinical outcomes and cartilage repair in osteoarthritis of the knee: a meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2019;139(7):971–980. doi: 10.1007/s00402-019-03140-8</mixed-citation></ref><ref id="B141"><label>141.</label><mixed-citation>Wu L, Prins HJ, Leijten JCH, et al. Chondrocytes cocultured with stromal vascular fraction of adipose tissue present more intense chondrogenic characteristics than with adipose stem cells. Tissue Eng Part A. 2016;22(3-4):336–348. doi: 10.1089/ten.TEA.2015.0269</mixed-citation></ref><ref id="B142"><label>142.</label><mixed-citation>Gupta PK, Das AK, Chullikana A, et al. Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther. 2012;3(4):25. doi: 10.1186/scrt116</mixed-citation></ref><ref id="B143"><label>143.</label><mixed-citation>Murphy JM, Fink DJ, Hunziker EB, et al. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48(12):3464–3474. doi: 10.1002/art.11365</mixed-citation></ref><ref id="B144"><label>144.</label><mixed-citation>Maumus M, Jorgensen C, Noël D. Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. Biochimie. 2013;95(12):2229–2234. doi: 10.1016/j.biochi.2013.04.017</mixed-citation></ref><ref id="B145"><label>145.</label><mixed-citation>Aletto C, Oliva F, Maffulli N. Knee intra-articular administration of stromal vascular fraction obtained from adipose tissue: a systematic review. J Clin Orthop Trauma. 2022;25:101773. doi: 10.1016/j.jcot.2022.101773</mixed-citation></ref><ref id="B146"><label>146.</label><mixed-citation>Michalek J, Moster R, Lukac L, et al. Stromal vascular fraction cells of adipose and connective tissue in people with osteoarthritis: a case control prospective multi-centric non-randomized study. Glob Surg. 2017;3(3):1–9. doi: 10.15761/GOS.1000163</mixed-citation></ref><ref id="B147"><label>147.</label><mixed-citation>Tsubosaka M, Matsumoto T, Sobajima S, et al. The influence of adipose-derived stromal vascular fraction cells on the treatment of knee osteoarthritis. BMC Musculoskelet Disord. 2020;21(1):207. doi: 10.1186/s12891-020-03231-3</mixed-citation></ref><ref id="B148"><label>148.</label><mixed-citation>Prizov A, Tchetina E, Eremin I, et al. Differences in synovial cytokine profile associated with long-term clinical outcomes in patients with knee osteoarthritis undergoing corrective osteotomy with platelet-rich plasma or stromal vascular fraction post-treatments. Int J Mol Sci. 2022;23(20):12835. doi: 10.3390/ijms232112835</mixed-citation></ref><ref id="B149"><label>149.</label><mixed-citation>Garza JR, Campbell RE, Tjoumakaris FP, et al. Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial. Am J Sports Med. 2020;48(3):588–598. doi: 10.1177/0363546519899923</mixed-citation></ref><ref id="B150"><label>150.</label><mixed-citation>Van Pham P, Bui KH, Duong TD, et al. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomed Res Ther. 2014;1(1):2–8. doi: 10.7603/s40730-014-0002-9</mixed-citation></ref><ref id="B151"><label>151.</label><mixed-citation>Mehranfar S, Abdi Rad I, Mostafavi E, et al. The use of stromal vascular fraction (SVF), platelet-rich plasma (PRP) and stem cells in the treatment of osteoarthritis: an overview of clinical trials. Artif Cells Nanomed Biotechnol. 2019;47(1):882–890. doi: 10.1080/21691401.2019.1576710</mixed-citation></ref><ref id="B152"><label>152.</label><mixed-citation>Diekman BO, Guilak F. Stem cell-based therapies for osteoarthritis: challenges and opportunities. Curr Opin Rheumatol. 2013;25(1):119–126. doi: 10.1097/BOR.0b013e32835aa28d</mixed-citation></ref><ref id="B153"><label>153.</label><mixed-citation>Magnanelli S, Screpis D, Di Benedetto P, et al. Open-wedge high tibial osteotomy associated with Lipogems® intra-articular injection for the treatment of varus knee osteoarthritis - retrospective study. Acta Biomed. 2020;91(14-S):e2020022. doi: 10.23750/abm.v91i14-S.10992</mixed-citation></ref><ref id="B154"><label>154.</label><mixed-citation>Kim YS, Koh YG. Comparative matched-pair analysis of open-wedge high tibial osteotomy with versus without an injection of adipose-derived mesenchymal stem cells for varus knee osteoarthritis: clinical and second-look arthroscopic results. Am J Sports Med. 2018;46(11):2669–2677. doi: 10.1177/0363546518785973</mixed-citation></ref><ref id="B155"><label>155.</label><mixed-citation>Kim YS, Suh DS, Tak DH, et al. Adipose-derived stromal vascular fractions are comparable with allogenic human umbilical cord blood-derived mesenchymal stem cells as a supplementary strategy of high tibial osteotomy for varus knee osteoarthritis. Arthrosc Sports Med Rehabil. 2023;5(3):e751–e764. doi: 10.1016/j.asmr.2023.04.002</mixed-citation></ref><ref id="B156"><label>156.</label><mixed-citation>Kim JH, Kim KI, Yoon WK, et al. Intra-articular injection of mesenchymal stem cells after high tibial osteotomy in osteoarthritic knee: two-year follow-up of randomized control trial. Stem Cells Transl Med. 2022;11(6):572–585. doi: 10.1093/stcltm/szac023</mixed-citation></ref><ref id="B157"><label>157.</label><mixed-citation>Sterett WI, Steadman JR, Huang MJ, et al. Chondral resurfacing and high tibial osteotomy in the varus knee: survivorship analysis. Am J Sports Med. 2010;38(7):1420–1424. doi: 10.1177/0363546509360403</mixed-citation></ref><ref id="B158"><label>158.</label><mixed-citation>Kim YS, Chung PK, Suh DS, et al. Implantation of mesenchymal stem cells in combination with allogenic cartilage improves cartilage regeneration and clinical outcomes in patients with concomitant high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. 2020;28(2):544–554. doi: 10.1007/s00167-019-05729-3</mixed-citation></ref><ref id="B159"><label>159.</label><mixed-citation>Zhang Q, Xu W, Wu K, et al. Intra-articular pure platelet-rich plasma combined with open-wedge high tibial osteotomy improves clinical outcomes and minimal joint space width compared with high tibial osteotomy alone in knee osteoarthritis: a prospective study. Arthroscopy. 2022;38(2):476–485. doi: 10.1016/j.arthro.2021.09.013</mixed-citation></ref><ref id="B160"><label>160.</label><mixed-citation>Koh YG, Kwon OR, Kim YS, et al. Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy. 2014;30(11):1453–1460. doi: 10.1016/j.arthro.2014.05.036</mixed-citation></ref><ref id="B161"><label>161.</label><mixed-citation>Prizov A, Tchetina E, Volkov A, et al. Long-term structural changes in the osteochondral unit in patients with osteoarthritis undergoing corrective osteotomy with platelet-rich plasma or stromal vascular fraction post-treatment. Biomedicines. 2024;12(5):1044. doi: 10.3390/biomedicines12051044</mixed-citation></ref><ref id="B162"><label>162.</label><mixed-citation>Ossendorff R, Menon A, Schildberg FA. A worldwide analysis of adipose-derived stem cells and stromal vascular fraction in orthopedics: current evidence and applications. J Clin Med. 2023;12(14):4719. doi: 10.3390/jcm12144719</mixed-citation></ref></ref-list></back></article>
