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Conventional treatments, primarily anti-inflammatories and immunosuppressants, provide partial relief but are often hampered by adverse effects and limited durability. Mesenchymal stem cells (MSCs) have emerged as a powerful new treatment due to their immunomodulatory and anti-inflammatory properties, primarily mediated through their secretome, which is a complex mixture of bioactive factors. Secretome-based therapeutic strategies show strong potential for controlling inflammation, mitigating oxidative stress, and supporting tissue regeneration and repair. However, the therapeutic efficacy of MSCs\u2019 secretome is subject to modification by concurrent anti-inflammatory drug regimens used in clinical settings. Methods: To evaluate the effect of combinatorial treatment strategies on the secretome of the MSCs, we employed an in vitro retinal inflammation model to investigate whether the exposure of the MSCs to five representative anti-inflammatory drugs (ketorolac, diclofenac, \u03b1-lipoic acid, N-acetyl-L-cysteine, and nicotinamide) impacts the functionality of the resulting secretome. Specifically, we evaluated the effect of the above-mentioned drugs on the anti-inflammatory properties of the secretome in relation to the secreted levels of two main MSC secretome factors\u2014the Brain-Derived Neurotrophic Factor (BDNF) and the Vascular Endothelial Growth Factor (VEGF)\u2014and on the secretome\u2019s pro-metabolic activity. Results: Our findings provide evidence that the presence of any of the tested drugs during MSC secretome production does not compromise its anti-inflammatory activity; BDNF and VEGF levels remain stable, and the secretome retains a high degree of its pro-metabolic effect. Conclusions: These results underscore the robustness and clinical resilience of MSC-based therapies, even when administered alongside pharmacological agents. This work advances the translational viability of MSC therapies for inflammatory diseases and supports the development of safe, combinatorial treatment strategies.<\/jats:p>","DOI":"10.3390\/pharmaceutics17091171","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:40:15Z","timestamp":1757407215000},"page":"1171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Preservation of the Therapeutic Efficacy of the Secretome of Adipose Mesenchymal Stem Cells, Produced in the Presence of Antioxidant and Anti-Inflammatory Drugs"],"prefix":"10.3390","volume":"17","author":[{"given":"Sofia","family":"Martinez-Rodriguez","sequence":"first","affiliation":[{"name":"Departamento de Cirug\u00eda, Oftalmolog\u00eda, Otorrinolaringolog\u00eda y Fisioterapia, Facultad de Medicina, Universidad de Valladolid, 47005 Valladolid, Spain"},{"name":"Instituto Universitario de Oftalmobiolog\u00eda Aplicada, Facultad de Medicina, Universidad de Valladolid, 47011 Valladolid, Spain"},{"name":"Silk Biomed SL, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahla","family":"Jemni-Damer","sequence":"additional","affiliation":[{"name":"Silk Biomed SL, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atocha","family":"Guedan-Duran","sequence":"additional","affiliation":[{"name":"Bioactive Surfaces SL, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9791-4057","authenticated-orcid":false,"given":"Girish K.","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Departamento de Cirug\u00eda, Oftalmolog\u00eda, Otorrinolaringolog\u00eda y Fisioterapia, Facultad de Medicina, Universidad de Valladolid, 47005 Valladolid, Spain"},{"name":"Instituto Universitario de Oftalmobiolog\u00eda Aplicada, Facultad de Medicina, Universidad de Valladolid, 47011 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0897-411X","authenticated-orcid":false,"given":"Fivos","family":"Panetsos","sequence":"additional","affiliation":[{"name":"Silk Biomed SL, 28049 Madrid, Spain"},{"name":"Bioactive Surfaces SL, 28049 Madrid, Spain"},{"name":"Neurocomputing and Neurorobotics Research Group, Faculty of Biology and Faculty of Optics, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Institute for Health Research San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain"},{"name":"Omnia Mater SL, 28049 Madrid, Spain"},{"name":"Human Retina SL, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12970","DOI":"10.1111\/sji.12970","article-title":"An inflammation classification system using cytokine parameters","volume":"93","author":"Roe","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3390\/cimb46010030","article-title":"Molecular Foundations of Inflammatory Diseases: Insights into Inflammation and Inflammasomes","volume":"46","author":"Kim","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.14218\/GE.2023.00061","article-title":"Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations","volume":"22","author":"Orekhov","year":"2023","journal-title":"Gene Expr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1101\/gad.183434.111","article-title":"NF-\u03baB, the first quarter-century: Remarkable progress and outstanding questions","volume":"26","author":"Hayden","year":"2012","journal-title":"Genes Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in biology and targeted therapy: New insights and translational implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s11658-023-00462-9","article-title":"The NLRP3 inflammasome: Contributions to inflammation-related diseases","volume":"28","author":"Chen","year":"2023","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11481-024-10101-5","article-title":"New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation","volume":"19","author":"Kodi","year":"2024","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s10753-021-01439-6","article-title":"The Signaling Pathways Regulating NLRP3 Inflammasome Activation","volume":"44","author":"Chen","year":"2021","journal-title":"Inflammation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.3390\/ph16091286","article-title":"Revisiting p38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis: A Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors (MK2i)","volume":"16","author":"Ganguly","year":"2023","journal-title":"Pharmaceuticals"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, X., Liu, R., and Liu, D. (2025). The Role of the MAPK Signaling Pathway in Cardiovascular Disease: Pathophysiological Mechanisms and Clinical Therapy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062667"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1161\/CIRCRESAHA.117.311401","article-title":"Reactive oxygen species in metabolic and inflammatory signaling","volume":"122","author":"Forrester","year":"2018","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Michalak, K.P., and Michalak, A.Z. (2025). Understanding chronic inflammation: Couplings between cytokines, ROS, NO, Cai2+, HIF-1\u03b1, Nrf2 and autophagy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1558263"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1126\/science.1230720","article-title":"Anti-Inflammatory Therapy in Chronic Disease: Challenges and Opportunities","volume":"339","author":"Tabas","year":"2013","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103410","DOI":"10.1016\/j.autrev.2023.103410","article-title":"Immune-mediated inflammatory diseases: Common and different pathogenic and clinical features","volume":"22","author":"Monteleone","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mishra, V.K., Shih, H.H., Parveen, F., Lenzen, D., Ito, E., Chan, T.F., and Ke, L.-Y. (2020). Identifying the therapeutic significance of mesenchymal stem cells. Cells, 9.","DOI":"10.3390\/cells9051145"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Eleuteri, S., and Fierabracci, A. (2019). Insights into the secretome of mesenchymal stem cells and its potential applications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184597"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"M\u00fczes, G., and Sipos, F. (2022). Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases. Cells, 11.","DOI":"10.3390\/cells11152300"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117899","DOI":"10.1016\/j.bmc.2024.117899","article-title":"Design, classification, and adverse effects of NSAIDs: A review on recent advancements","volume":"112","author":"Arfeen","year":"2024","journal-title":"Bioorg. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Tunger, A., Wobus, M., von Bonin, M., Towers, R., Bornh\u00e4user, M., Dazzi, F., Wehner, R., and Schmitz, M. (2021). Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.637725"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s13075-023-03185-6","article-title":"The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis","volume":"25","author":"Bruckner","year":"2023","journal-title":"Arthritis Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13287-024-04062-y","article-title":"Efficacy of umbilical cord-derived mesenchymal stem cells and exosomes in conjunction with standard IBD drug on immune responses in an IBD mouse model","volume":"16","author":"Kheradmand","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s13287-024-03765-6","article-title":"Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: Results from a phase II, randomized, placebo-controlled clinical trial","volume":"15","author":"Harris","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12015-021-10231-w","article-title":"Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years?","volume":"18","author":"Galderisi","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s13287-024-03885-z","article-title":"Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: Challenges and opportunities","volume":"15","author":"Zhidu","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lim, S.U., Lee, D.W., Kim, J.H., Kang, Y.J., Kim, I.Y., and Oh, I.H. (2024). Chemical Coaxing of Mesenchymal Stromal Cells by Drug Repositioning for Nestin Induction. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158006"},{"key":"ref_27","first-page":"S233","article-title":"Current Status of the Applications of Conditioned Media Derived from Mesenchymal Stem Cells for Regenerative Medicine","volume":"72","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12929-018-0407-7","article-title":"Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs","volume":"25","author":"Somaiah","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ferreira, J.R., Teixeira, G.Q., Santos, S.G., Barbosa, M.A., Almeida-Porada, G., and Gon\u00e7alves, R.M. (2018). Mesenchymal stromal cell secretome: Influencing therapeutic potential by cellular pre-conditioning. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02837"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Blagov, A.V., Summerhill, V.I., Sukhorukov, V.N., Zhigmitova, E.B., Postnov, A.Y., and Orekhov, A.N. (2024). Potential use of antioxidants for the treatment of chronic inflammatory diseases. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1378335"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.bbagen.2009.07.026","article-title":"Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential","volume":"1790","author":"Shay","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8555","DOI":"10.1021\/jm201090k","article-title":"Binding of Ibuprofen, Ketorolac, and Diclofenac to COX-1 and COX-2 Studied by Saturation Transfer Difference NMR","volume":"54","author":"Viegas","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107916","DOI":"10.1016\/j.pharmthera.2021.107916","article-title":"The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species","volume":"228","author":"Pedre","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tribble, J.R., Otmani, A., Sun, S., Ellis, S.A., Cimaglia, G., Vohra, R., J\u00f6e, M., Lardner, E., Venkataraman, A.P., and Dom\u00ednguez-Vicent, A. (2021). Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biol., 43.","DOI":"10.1016\/j.redox.2021.101988"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/jcp.24815","article-title":"Cyclooxygenase-2 regulates NLRP3 inflammasome-derived IL-1\u03b2 production","volume":"230","author":"Hua","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12515","DOI":"10.1096\/fj.201802805RR","article-title":"Activation of ROS\/MAPKs\/NF-\u03baB\/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis","volume":"33","author":"An","year":"2019","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jare.2023.01.001","article-title":"Canonical and non-canonical functions of NLRP3","volume":"53","author":"Accogli","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Charlton, T., Prowse, N., McFee, A., Heiratifar, N., Fortin, T., Paquette, C., and Hayley, S. (2023). Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1188672"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wheeler, K.C., Jena, M.K., Pradhan, B.S., Nayak, N., Das, S., Hsu, C.D., Wheeler, D.S., Chen, K., and Nayak, N.R. (2018). VEGF may contribute to macrophage recruitment and M2 polarization in the decidua. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191040"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.biopha.2017.10.126","article-title":"The effect of ketorolac and triamcinolone acetonide on adipogenic and hepatogenic differentiation through miRNAs 16\/15\/195: Possible clinical application in regenerative medicine","volume":"97","author":"Aval","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1158\/1535-7163.MCT-15-0419","article-title":"R-ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis","volume":"14","author":"Guo","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1128\/IAI.66.5.2290-2299.1998","article-title":"Effects of the antioxidant \u03b1-lipoic acid on human umbilical vein endothelial cells infected with Rickettsia rickettsii","volume":"66","author":"Eremeeva","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dieter, F., Esselun, C., and Eckert, G.P. (2022). Redox Active \u03b1-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169186"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1007\/s12035-017-0575-6","article-title":"Effect of Lipoic Acid on the Biochemical Mechanisms of Resistance to Bortezomib in SH-SY5Y Neuroblastoma Cells","volume":"55","author":"Tibullo","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1256","DOI":"10.1002\/lio2.1256","article-title":"N-acetylcysteine microparticles reduce cisplatin-induced RSC96 Schwann cell toxicity","volume":"9","author":"Kedeshian","year":"2024","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1007\/s00405-024-08622-z","article-title":"An in vitro model for postoperative cranial nerve dysfunction and a proposed method of rehabilitation with N-acetylcysteine microparticles","volume":"281","author":"Kita","year":"2024","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhou, J., Terluk, M.R., Basso, L., Mishra, U.R., Orchard, P.J., Cloyd, J.C., Schr\u00f6der, H., and Kartha, R.V. (2020). N-acetylcysteine provides cytoprotection in murine oligodendrocytes through heme oxygenase-1 activity. Biomedicines, 8.","DOI":"10.3390\/biomedicines8080240"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kida, T., Kozai, S., Takahashi, H., Isaka, M., Tokushige, H., and Sakamoto, T. (2014). Pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs in retinochoroidal tissues in rabbits. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096481"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1210\/jcem.83.1.4478","article-title":"Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy","volume":"83","author":"Hiromatsu","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12929-019-0555-4","article-title":"Correction to: Reactive oxygen speciesdependent mitochondrial dynamics and autophagy confer protective effects in retinal pigment epithelial cells against sodium iodate-induced cell death","volume":"26","author":"Chan","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3390\/s30800276","article-title":"Measurement of Nitric Oxide Production in Biological Systems by Using Griess Reaction Assay","volume":"3","author":"Sun","year":"2003","journal-title":"Sensors"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5961123","DOI":"10.1155\/2022\/5961123","article-title":"Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE","volume":"2022","author":"Ren","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Martinez-Gil, N., Vidal-Gil, L., Flores-Bellver, M., Maisto, R., Sancho-Pelluz, J., Diaz-Llopis, M., Barcia, J.M., and Romero, F.J. (2020). Ethanol-induced oxidative stress modifies inflammation and angiogenesis biomarkers in retinal pigment epithelial cells (Arpe-19): Role of cyp2e1 and its inhibition by antioxidants. Antioxidants, 9.","DOI":"10.3390\/antiox9090776"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0022-1759(91)90114-U","article-title":"An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT","volume":"142","author":"Roehm","year":"1991","journal-title":"J. Immunol. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41581-018-0023-5","article-title":"Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases","volume":"14","author":"Shi","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chen, B., Chen, Z., He, M., Zhang, L., Yang, L., and Wei, L. (2024). Recent advances in the role of mesenchymal stem cells as modulators in autoinflammatory diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1525380"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.trim.2011.06.002","article-title":"Features of synergism between mesenchymal stem cells and immunosuppressive drugs in a murine heart transplantation model","volume":"25","author":"Eggenhofer","year":"2011","journal-title":"Transpl. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1177\/03635465221083610","article-title":"NSAIDs Reduce Therapeutic Efficacy of Mesenchymal Stromal Cell Therapy in a Rodent Model of Posttraumatic Osteoarthritis","volume":"50","author":"Sok","year":"2022","journal-title":"Am. J. Sports Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1007\/s10787-023-01350-6","article-title":"Innovative preconditioning strategies for improving the therapeutic efficacy of extracellular vesicles derived from mesenchymal stem cells in gastrointestinal diseases","volume":"31","author":"Didamoony","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13287-022-02747-w","article-title":"Enhancement strategies for mesenchymal stem cells and related therapies","volume":"13","author":"Alagesan","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sarsenova, M., Kim, Y., Raziyeva, K., Kazybay, B., Ogay, V., and Saparov, A. (2022). Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1010399"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cavallero, S., Dekali, S., Guitard, N., Th\u00e9ry, H., H\u00e9lissey, C., and Fran\u00e7ois, S. (2023). Effects of preconditioning with TNF\u03b1 and IFN\u03b3 in angiogenic potential of mesenchymal stromal cell-derived extracellular vesicles. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1291016"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40634-019-0185-5","article-title":"Absence of cytotoxic and inflammatory effects following in vitro exposure of mesenchymal stem cells to adenosine, lidocaine and Mg2+ solution","volume":"5","author":"Mccutchan","year":"2019","journal-title":"J. Exp. Orthop."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"120633","DOI":"10.1016\/j.biomaterials.2020.120633","article-title":"Dissecting the effects of preconditioning with inflammatory cytokines and hypoxia on the angiogenic potential of mesenchymal stromal cell (MSC)-derived soluble proteins and extracellular vesicles (EVs)","volume":"269","author":"Gorgun","year":"2021","journal-title":"Biomaterials"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.3892\/mmr.2016.5416","article-title":"Low levels of TGF-\u03b21 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury","volume":"14","author":"Li","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s13287-022-03121-6","article-title":"Therapeutic potential of conditioned medium obtained from deferoxamine preconditioned umbilical cord mesenchymal stem cells on diabetic nephropathy model","volume":"13","author":"Ozkan","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13287-020-01677-9","article-title":"Inflammatory priming enhances mesenchymal stromal cell secretome potential as a clinical product for regenerative medicine approaches through secreted factors and EV-miRNAs: The example of joint disease","volume":"11","author":"Ragni","year":"2020","journal-title":"Stem Cell Res. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/9\/1171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:42:03Z","timestamp":1760035323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/9\/1171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":67,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["pharmaceutics17091171"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17091171","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}