{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:17:11Z","timestamp":1787944631258,"version":"build-2784847793"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The <jats:italic>in vivo<\/jats:italic> therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the <jats:italic>in vivo<\/jats:italic> OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.<\/jats:p>","DOI":"10.3389\/fbioe.2024.1359212","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:45:59Z","timestamp":1707713159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["One-step stromal vascular fraction therapy in osteoarthritis with tropoelastin-enhanced autologous stromal vascular fraction gel"],"prefix":"10.3389","volume":"12","author":[{"given":"Junjun","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XueBao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.3390\/biom11091318","article-title":"Tropoelastin promotes the formation of dense, interconnected endothelial networks","volume":"11","author":"Al Halawani","year":"2021","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"19830","DOI":"10.1021\/acsami.9b04616","article-title":"Tropoelastin-coated tendon biomimetic scaffolds promote stem cell tenogenic commitment and deposition of elastin-rich matrix","volume":"11","author":"Almeida","year":"2019","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/prs.0000000000010483","article-title":"Adipose component transplantation - an advanced fat grafting strategy based on adipose tissue component selection for facial rejuvenation","author":"Cai","year":"","journal-title":"Plast. Reconstr. Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1097\/prs.0000000000006456","article-title":"Mechanical micronization of lipoaspirates for the treatment of horizontal neck lines","volume":"145","author":"Cai","year":"2020","journal-title":"Plast. Reconstr. Surg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s13287-023-03389-2","article-title":"Long-term follow-up and exploration of the mechanism of stromal vascular fraction gel in chronic wounds","volume":"14","author":"Cai","year":"","journal-title":"Stem Cell Res. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1038\/s12276-021-00710-y","article-title":"Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions","volume":"53","author":"Cho","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1007\/s00296-018-4099-9","article-title":"Comparative short-term effectiveness of ibuprofen gel and cream phonophoresis in patients with knee osteoarthritis","volume":"38","author":"Coskun Benlidayi","year":"2018","journal-title":"Rheumatol. Int."},{"key":"B8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2165\/11595680-000000000-00000","article-title":"Evaluation and treatment of disorders of the infrapatellar fat pad","volume":"42","author":"Dragoo","year":"2012","journal-title":"Sports Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1111\/joim.13634","article-title":"Osteoarthritis, part of life or a curable disease? A bird's-eye view","volume":"293","author":"Englund","year":"2023","journal-title":"J. Intern Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1093\/rheumatology\/keu377","article-title":"Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis","volume":"54","author":"Eseonu","year":"2015","journal-title":"Rheumatol. Oxf."},{"key":"B11","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.joca.2023.03.008","article-title":"Osteoarthritis year in review 2022: epidemiology & therapy","volume":"31","author":"Foster","year":"2023","journal-title":"Osteoarthr. Cartil."},{"key":"B12","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.stem.2018.05.004","article-title":"Mesenchymal stromal cells: clinical challenges and therapeutic opportunities","volume":"22","author":"Galipeau","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13287-017-0719-7","article-title":"Pellet coculture of osteoarthritic chondrocytes and infrapatellar fat pad-derived mesenchymal stem cells with chitosan\/hyaluronic acid nanoparticles promotes chondrogenic differentiation","volume":"8","author":"Huang","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"631291","DOI":"10.3389\/fimmu.2021.631291","article-title":"Recent developments in clinical applications of mesenchymal stem cells in the treatment of rheumatoid arthritis and osteoarthritis","volume":"12","author":"Hwang","year":"2021","journal-title":"Front. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.ijsu.2017.08.557","article-title":"Hip arthroscopy: indications, outcomes and complications","volume":"54","author":"Jamil","year":"2018","journal-title":"Int. J. Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cps.2019.09.001","article-title":"Fat grafting for facial rejuvenation using stromal vascular fraction gel injection","volume":"47","author":"Jiang","year":"2020","journal-title":"Clin. Plast. Surg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1097\/prs.0000000000009435","article-title":"Adipose-derived stem cell-enriched lipotransfer reverses skin sclerosis by suppressing dermal inflammation","volume":"150","author":"Jiang","year":"2022","journal-title":"Plast. Reconstr. Surg."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1118850","DOI":"10.3389\/fbioe.2023.1118850","article-title":"Sustained intra-articular reactive oxygen species scavenging and alleviation of osteoarthritis by biocompatible amino-modified tantalum nanoparticles","volume":"11","author":"Jiang","year":"2023","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1126\/science.1215157","article-title":"A stem cell-based approach to cartilage repair","volume":"336","author":"Johnson","year":"2012","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","first-page":"121370","DOI":"10.1016\/j.biomaterials.2022.121370","article-title":"Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis","volume":"281","author":"Katyal","year":"2022","journal-title":"Biomaterials"},{"key":"B21","doi-asserted-by":"publisher","first-page":"931","DOI":"10.7150\/thno.78639","article-title":"Targeted and responsive biomaterials in osteoarthritis","volume":"13","author":"Li","year":"2023","journal-title":"Theranostics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"694","DOI":"10.3389\/fcell.2020.00694","article-title":"Autologous fractionated adipose tissue as a natural biomaterial and novel one-step stem cell therapy for repairing articular cartilage defects","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13075-020-02193-0","article-title":"Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK\/PI3K\/AKT signaling pathway","volume":"22","author":"Liu","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1007\/s00167-018-5118-9","article-title":"Injective mesenchymal stem cell-based treatments for knee osteoarthritis: from mechanisms of action to current clinical evidences","volume":"27","author":"Lopa","year":"2019","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"B25","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s13287-021-02265-1","article-title":"Mesenchymal stem\/stromal cells as a valuable source for the treatment of immune-mediated disorders","volume":"12","author":"Markov","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"7205","DOI":"10.1039\/d1bm00727k","article-title":"Self-assembled lyotropic liquid crystal gel for osteoarthritis treatment via anti-inflammation and cartilage protection","volume":"9","author":"Mei","year":"2021","journal-title":"Biomater. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3390\/jfb14040203","article-title":"Tropoelastin-pretreated exosomes from adipose-derived stem cells improve the synthesis of cartilage matrix and alleviate osteoarthritis","volume":"14","author":"Meng","year":"2023","journal-title":"J. Funct. Biomater."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1701206","DOI":"10.1002\/adhm.201701206","article-title":"Tropoelastin implants that accelerate wound repair","volume":"7","author":"Mithieux","year":"2018","journal-title":"Adv. Healthc. Mater"},{"key":"B29","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.addr.2012.06.009","article-title":"Tropoelastin--a multifaceted naturally smart material","volume":"65","author":"Mithieux","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1007\/s00167-015-3701-x","article-title":"Knee arthroscopy: the science of art","volume":"23","author":"Nyland","year":"2015","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"112533","DOI":"10.1016\/j.msec.2021.112533","article-title":"Autologous stromal vascular fraction-loaded hyaluronic acid\/gelatin-biphasic calcium phosphate scaffold for bone tissue regeneration","volume":"132","author":"Park","year":"2022","journal-title":"Mater Sci. Eng. C Mater Biol. Appl."},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13018-024-04532-2","article-title":"Exercise-induced modulation of myokine irisin on muscle-bone unit in the rat model of post-traumatic osteoarthritis","volume":"19","author":"Shang","year":"2024","journal-title":"J. Orthop. Surg. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"j1982","DOI":"10.1136\/bmj.j1982","article-title":"Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline","volume":"357","author":"Siemieniuk","year":"2017","journal-title":"Bmj"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1089\/ten.tea.2017.0502","article-title":"Photocrosslinkable gelatin\/tropoelastin hydrogel adhesives for peripheral nerve repair","volume":"24","author":"Soucy","year":"2018","journal-title":"Tissue Eng. Part A"},{"key":"B35","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1007\/s00266-022-03065-5","article-title":"SVF-GEL cryopreserved for different times exhibits varied preservation and regeneration potential after transplantation in a mouse model","volume":"47","author":"Tao","year":"2023","journal-title":"Aesthetic Plast. Surg."},{"key":"B36","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13287-019-1140-1","article-title":"Mechanical micronization of lipoaspirates for the treatment of hypertrophic scars","volume":"10","author":"Wang","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1007\/s11427-014-4673-7","article-title":"Treatment of osteoarthritis with mesenchymal stem cells","volume":"57","author":"Wang","year":"2014","journal-title":"Sci. China Life Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.actbio.2013.08.003","article-title":"Tropoelastin: a versatile, bioactive assembly module","volume":"10","author":"Wise","year":"2014","journal-title":"Acta Biomater."},{"key":"B39","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.biomaterials.2019.03.022","article-title":"miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis","volume":"206","author":"Wu","year":"2019","journal-title":"Biomaterials"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/9054514","article-title":"Promotion of hair growth by conditioned medium from extracellular matrix\/stromal vascular fraction gel in C57bl\/6 mice","volume":"2020","author":"Xiao","year":"2020","journal-title":"Stem Cells Int."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e2207490","DOI":"10.1002\/advs.202207490","article-title":"Nanomedicines reprogram synovial macrophages by scavenging nitric oxide and silencing CA9 in progressive osteoarthritis","volume":"10","author":"Yan","year":"2023","journal-title":"Adv. Sci. (Weinh)."},{"key":"B42","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1016\/j.freeradbiomed.2020.01.185","article-title":"Natural ingredients-derived antioxidants attenuate H(2)O(2)-induced oxidative stress and have chondroprotective effects on human osteoarthritic chondrocytes via Keap1\/Nrf2 pathway","volume":"152","author":"Yang","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.bioactmat.2021.09.011","article-title":"Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression","volume":"10","author":"Yang","year":"2022","journal-title":"Bioact. Mater"},{"key":"B44","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"638415","DOI":"10.3389\/fbioe.2021.638415","article-title":"Phenotypic and cellular characteristics of a stromal vascular fraction\/extracellular matrix gel prepared using mechanical shear force on human fat","volume":"9","author":"Ye","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1073\/pnas.1812951116","article-title":"Soluble matrix protein is a potent modulator of mesenchymal stem cell performance","volume":"116","author":"Yeo","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B47","doi-asserted-by":"publisher","first-page":"101684","DOI":"10.1016\/j.arr.2022.101684","article-title":"Research progress in the use of mesenchymal stem cells and their derived exosomes in the treatment of osteoarthritis","volume":"80","author":"Yu","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.14336\/ad.2019.1116","article-title":"Infrapatellar fat pad and knee osteoarthritis","volume":"11","author":"Zeng","year":"2020","journal-title":"Aging Dis."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2024.1359212\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:46:02Z","timestamp":1707713162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2024.1359212\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,12]]},"references-count":48,"alternative-id":["10.3389\/fbioe.2024.1359212"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2024.1359212","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,12]]},"article-number":"1359212"}}