Cell and Organ Transplantology. 2025; 13(2):e2025132184.
DOI: 10.22494/cot.v13-2.184
Adipose tissue dysfunction under inflammatory conditions and possibilities for its correction using cell therapy
Ivanishchev V.1
, Ustymenko A.1,2![]()
- 1D. F. Chebotarev State Institute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
- 2M. D. Strazhesko National Scientific Center of Cardiology, Clinical and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Abstract
Adipose tissue dysfunction under inflammatory conditions is a key pathogenetic factor in the development of metabolic and systemic disorders, including systemic inflammatory response syndrome (SIRS) and chronic inflammatory processes. This review summarizes current clinical and experimental evidence on the functional, morphological, and molecular alterations in adipose tissue under acute and chronic inflammation.
The data indicate that inflammatory conditions disrupt the secretory activity of adipocytes and adipose tissue-derived mesenchymal stromal cells (MSCs), leading to increased production of pro-inflammatory cytokines, chemokines, and other mediators. The resulting pro-inflammatory microenvironment adversely affects MSCs, reducing their proliferative and differentiation capacity, impairing regenerative potential, and causing telomere shortening associated with cellular aging. The role of immune cells, particularly macrophages, in sustaining chronic inflammation and promoting adipose tissue dysfunction is also highlighted.
Special attention is given to current strategies for mitigating inflammation-induced adipose tissue alterations using cell-based therapy. MSCs, due to their immunomodulatory, anti-inflammatory, and regenerative properties, represent a promising approach for restoring adipose tissue homeostasis and alleviating systemic inflammation.
Conclusion. Acute and chronic inflammation induces profound changes in adipocyte and MSC function, impairing the regulatory and reparative capacity of adipose tissue. MSC-based therapy holds potential for correcting adipose tissue dysfunction under inflammatory conditions, but further studies are needed to elucidate mechanisms of action, optimize treatment protocols, and evaluate long-term safety and efficacy.
Key words: systemic inflammatory response syndrome; chronic inflammation; adipose tissue; adipose-derived mesenchymal stem cells; immunomodulation; cell therapy
Full text PDF
-
1. Chavda VP, Feehan J, Apostolopoulos V. Inflammation: The Cause of All Diseases. Cells. 2024; 13(22):1906. https://doi.org/10.3390/cells13221906
https://doi.org/10.3390/cells13221906
PMid:39594654 PMCid:PMC115925572. Vasileia Ismini Alexaki. Adipose tissue-derived mediators of systemic inflammation and metabolic control. Curr Opin Endocr Metab Res. 2024; 37. https://doi.org/10.1016/j.coemr.2024.100560
https://doi.org/10.1016/j.coemr.2024.1005603. Soták M, Clark M, Suur BE, et al. Inflammation and resolution in obesity. Nat Rev Endocrinol. 2025; 21:45-61. https://doi.org/10.1038/s41574-024-01047-y
https://doi.org/10.1038/s41574-024-01047-y
PMid:394488304. Savulescu-Fiedler I, Mihalcea R, Dragosloveanu S, Scheau C, Baz RO, Caruntu A, Scheau AE, et al. The Interplay between Obesity and Inflammation. Life. 2024; 14:856. https://doi.org/10.3390/life14070856
https://doi.org/10.3390/life14070856
PMid:39063610 PMCid:PMC112779975. Turner L, Wanasinghe A, Brunori P, Santosa S. Is Adipose Tissue Inflammation the Culprit of Obesity-Associated Comorbidities? Obesity Reviews. 2025; 26(11):e13956, https://doi.org/10.1111/obr.13956
https://doi.org/10.1111/obr.13956
PMid:40533358 PMCid:PMC125317536. Palanivel JA, Millington GWM. Obesity-induced immunological effects on the skin. Skin Health Dis. 2023; 3(3):e160. https://doi.org/10.1002/ski2.160
https://doi.org/10.1002/ski2.160
PMid:37275420 PMCid:PMC102330917. Unamuno X, Frühbeck G, Catalán V. Adipose Tissue. In: Encyclopedia of Endocrine Diseases. Elsevier; 2019:370-384.
https://doi.org/10.1016/B978-0-12-801238-3.65163-28. Li J, Li Y, Zhou X., et al. Adipocytes orchestrate obesity-related chronic inflammation through β2-microglobulin. Sig Transduct Target Ther. 2025; 10:394. https://doi.org/10.1038/s41392-025-02486-3
https://doi.org/10.1038/s41392-025-02486-3
PMid:41330906 PMCid:PMC126725739. https://my.clevelandclinic.org/health/body/24052-adipose-tissue-body-fat 10. Zhang M, Hu T, Zhang S, et al. Associations of Different Adipose Tissue Depots with Insulin Resistance: A Systematic Review and Meta-analysis of Observational Studies. Sci Rep. 2015; 5:18495. https://doi.org/10.1038/srep1849
https://doi.org/10.1038/srep18495
PMid:26686961 PMCid:PMC468519511. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, et al. Dynamics of fat cell turnover in humans. Nature. 2008; 453(7196):783-7. https://doi.org/10.1038/nature06902
https://doi.org/10.1038/nature06902
PMid:1845413612. Dichi I, Simão AN, Vannucchi H, Curi R, Calder PC. Metabolic syndrome: epidemiology, pathophysiology, and nutrition intervention. J Nutr Metab. 2012; 2012:584541.
https://doi.org/10.1155/2012/584541
PMid:22778922 PMCid:PMC338495813. Bensussen A, Torres-Magallanes JA and Roces de Álvarez-Buylla E Molecular tracking of insulin resistance and inflammation development on visceral adipose tissue. Front. Immunol. 2023; 14:1014778. https://doi.org/10.3389/fimmu.2023.1014778
https://doi.org/10.3389/fimmu.2023.1014778
PMid:37026009 PMCid:PMC1007094714. Zhang Y, Gao W, Li B, et al. The association between the visceral obesity indices and the future diabetes mellitus risk: A prospective cohort study. Diabetes Obes Metab. 2025; 27(8): 4490-4498. https://doi.org/10.1111/dom.16492
https://doi.org/10.1111/dom.16492
PMid:4043237815. Lin M, Zhou Y, Wu R, Li S, Ni X, Xiao J, et al. Temporal Relationship Between Visceral Fat and Inflammation, and Their Joint Effect on Cardiometabolic Diseases: Evidence from the China Health and Retirement Longitudinal Study (CHARLS). J Inflamm Res. 2025; 18:14913-14926. https://doi.org/10.2147/JIR.S539644
https://doi.org/10.2147/JIR.S539644
PMid:41181368 PMCid:PMC1257763416. Bettinetti-Luque M, Trujillo-Estrada L, Garcia-Fuentes E, Andreo-Lopez J, Sanchez-Varo R, Garrido-Sánchez L, et al. Adipose tissue as a therapeutic target for vascular damage in Alzheimer’s disease. British Journal of Pharmacology. 2024; 181(6):840-878. https://doi.org/10.1111/bph.16243
https://doi.org/10.1111/bph.16243
PMid:3770634617. 17. Gemma Alderton. Obesity and inflammation. Science.2020;370(6515):419.1-419 https://doi.org/10.1126/science.370.6515.419-a
https://doi.org/10.1126/science.370.6515.419-a18. Ming Ma, Wei Jiang, Rongbin Zhou. DAMPs and DAMP-sensing receptors in inflammation and diseases. Immunity. 2024; 57(4). https://doi.org/10.1016/j.immuni.2024.03.002
https://doi.org/10.1016/j.immuni.2024.03.002
PMid:3859916919. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat Immunol. 2010; 11:373-384. https://doi.org/10.1038/ni.1863
https://doi.org/10.1038/ni.1863
PMid:2040485120. Kaur S, Auger C, Jeschke MG. Adipose tissue metabolic function and dysfunction: impact of burn injury. Front Cell Dev Biol. 2020; 8:599576. https://doi.org/10.3389/fcell.2020.599576
https://doi.org/10.3389/fcell.2020.599576
PMid:33251224 PMCid:PMC767639921. Sikora JP, Karawani J, Sobczak J. Neutrophils and the Systemic Inflammatory Response Syndrome (SIRS). International Journal of Molecular Sciences. 2023; 24(17):13469. https://doi.org/10.3390/ijms241713469
https://doi.org/10.3390/ijms241713469
PMid:37686271 PMCid:PMC1048803622. Baddam S, Burns B. Systemic Inflammatory Response Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2025. https://www.ncbi.nlm.nih.gov/books/NBK547669/ 23. Shrestha M, Kumar M. Systemic inflammatory response syndrome: the current status. November Journal of Universal College of Medical Sciences. 2018; 6(1):56 https://doi.org/10.3126/jucms.v6i1.21732
https://doi.org/10.3126/jucms.v6i1.2173224. Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets – an updated view. Mediators Inflamm. 2013; 2013:165974. https://doi.org/10.1155/2013/165974
https://doi.org/10.1155/2013/165974
PMid:23853427 PMCid:PMC3703895https://my.clevelandclinic.org/health/diseases/multiple-organ-dysfunction-syndrome 26. 26. Wrba L, Halbgebauer R, Roos J, et al. Adipose tissue: a neglected organ in the response to severe trauma?. Cell Mol Life Sci. 2022; 79(207). https://doi.org/10.1007/s00018-022-04234-0
https://doi.org/10.1007/s00018-022-04234-0
PMid:35338424 PMCid:PMC895655927. Pachler C, Ikeoka D, Plank J, Weinhandl H, Suppan M, Mader JK, et al. Subcutaneous adipose tissue exerts proinflammatory cytokines after minimal trauma in humans. Am J Physiol Endocrinol Metab. 2007; 293(3):E690-6. https://doi.org/10.1152/ajpendo.00034.2007
https://doi.org/10.1152/ajpendo.00034.2007
PMid:1757889028. Prasai A, El Ayadi A, Mifflin RC, Wetzel MD, Andersen CR, Redl H, et al. Characterization of Adipose-Derived Stem Cells Following Burn Injury. Stem Cell Rev Rep. 2017; 13(6):781-792. https://doi.org/10.1007/s12015-017-9721-9
https://doi.org/10.1007/s12015-017-9721-9
PMid:28646271 PMCid:PMC573063629. Saraf MK, Herndon DN, Porter C, Toliver-Kinsky T, Radhakrishnan R, Chao T, et al. Morphological Changes in Subcutaneous White Adipose Tissue After Severe Burn Injury. J Burn Care Res. 2016; 37(2):e96-103. https://doi.org/10.1097/BCR.0000000000000292
https://doi.org/10.1097/BCR.0000000000000292
PMid:26284641 PMCid:PMC474944830. Charles-Messance H, Mitchelson KAJ, De Marco Castro E, Sheedy FJ, Roche HM. Regulating metabolic inflammation by nutritional modulation. J Allergy Clin Immunol. 2020; 146(4):706-720. https://doi.org/10.1016/j.jaci.2020.08.013
https://doi.org/10.1016/j.jaci.2020.08.013
PMid:3284165231. Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021; 320(3):C375-C391. https://doi.org/0.1152/ajpcell.00379.2020
https://doi.org/10.1152/ajpcell.00379.2020
PMid:33356944 PMCid:PMC829462432. Sebo ZL, Rodeheffer MS. Assembling the adipose organ: Adipocyte lineage segragation and adipogenesis in vivo. Development. 2019; 146:dev172098. https://doi.org/10.1242/dev.172098
https://doi.org/10.1242/dev.172098
PMid:30948523 PMCid:PMC646747433. Rutkowski JM, Stern JH, Scherer PE. The cell biology of fat expansion. J Cell Biol. 2015; 208(5):501‐512. https://doi.org/10.1083/jcb.201409063
https://doi.org/10.1083/jcb.201409063
PMid:25733711 PMCid:PMC434764434. Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res. 2009; 48(5):275-97. https://doi.org/10.1016/j.plipres.2009.05.001
https://doi.org/10.1016/j.plipres.2009.05.001
PMid:1946431835. Lee YS, Li P, Huh JY, Hwang IJ, Lu M, Kim JI, et al. Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes. 2011; 60: 2474-2483. https://doi.org/10.2337/db11-0194
https://doi.org/10.2337/db11-0194
PMid:21911747 PMCid:PMC317829736. Trayhurn P, Wood IS. Adipokines: Inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004; 92:347-355. https://doi.org/10.1079/bjn20041213
https://doi.org/10.1079/BJN20041213
PMid:1546963837. Mohammed Saeed W, Nasser Binjawhar D. Association of Serum Leptin and Adiponectin Concentrations with Type 2 Diabetes Biomarkers and Complications Among Saudi Women. Diabetes Metab Syndr Obes. 2023; 16:2129-2140. https://doi.org/10.2147/DMSO.S405476
https://doi.org/10.2147/DMSO.S405476
PMid:37465649 PMCid:PMC1035152238. Chang Liu, Xiaojiao Li, Role of leptin and adiponectin in immune response and inflammation, International Immunopharmacology. 2025; 161. https://doi.org/10.1016/j.intimp.2025.115082
https://doi.org/10.1016/j.intimp.2025.115082
PMid:4051625539. Hong X, Zhang X, You L, Li F, Lian H, Wang J, et al. Association between adiponectin and newly diagnosed type 2 diabetes in population with the clustering of obesity, dyslipidaemia and hypertension: a cross-sectional study. BMJ Open. 2023; 13(2):e060377. https://doi.org/10.1136/bmjopen-2021-060377
https://doi.org/10.1136/bmjopen-2021-060377
PMid:36828662 PMCid:PMC997240940. Buechler C, Feder S, Haberl EM, Aslanidis C. Chemerin Isoforms and Activity in Obesity. Int J Mol Sci. 2019; 20(5):1128. https://doi.org/10.3390/ijms20051128
https://doi.org/10.3390/ijms20051128
PMid:30841637 PMCid:PMC642939241. Jialal I. Chemerin levels in metabolic syndrome: a promising biomarker. Arch Physiol Biochem. 2023; 129(5):1009-1011. https://doi.org/10.1080/13813455.2021.1912103
https://doi.org/10.1080/13813455.2021.1912103
PMid:3384339742. Gutierrez-Rodelo C, Arellano-Plancarte A, Hernandez-Aranda J, Landa-Galvan HV, Parra-Mercado GK, Moreno-Licona NJ, et al. Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells. International Journal of Molecular Sciences. 2022; 23(11):6048. https://doi.org/10.3390/ijms23116048
https://doi.org/10.3390/ijms23116048
PMid:35682723 PMCid:PMC918164243. Munno M, Mallia A, Greco A, Modafferi G, Banfi C, Eligini S. Radical Oxygen Species, Oxidized Low-Density Lipoproteins, and Lectin-like Oxidized Low-Density Lipoprotein Receptor 1: A Vicious Circle in Atherosclerotic Process. Antioxidants (Basel). 2024; 13(5):583. https://doi.org/10.3390/antiox13050583
https://doi.org/10.3390/antiox13050583
PMid:38790688 PMCid:PMC1111816844. Craige SM, Kaur G, Bond JM, Caliz AD, Kant S, Keaney JF. Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease. ARS. Redox Signaling. 2025; 42(16-18):905-932. https://doi.org/10.1089/ars.2024.0706
https://doi.org/10.1089/ars.2024.0706
PMid:3921316145. Rabiee A, Hossain MA, Poojari A. Adipose Tissue Insulin Resistance: A Key Driver of Metabolic Syndrome Pathogenesis. Biomedicines. 2025; 13(10):2376. https://doi.org/10.3390/biomedicines13102376
https://doi.org/10.3390/biomedicines13102376
PMid:41153663 PMCid:PMC1256139246. Dhakad PK, Mishra R, Mishra I. Toll-like receptor expression during inflammatory processes in human diseases. Rheumatol Autoimmun. 2025; 5:1-14. https://doi.org/10.1002/rai2.12167
https://doi.org/10.1002/rai2.1216747. Campos-Bayardo TI, Román-Rojas D, García-Sánchez A, Cardona-Muñoz EG, Sánchez-Lozano DI, Totsuka-Sutto S, et al. The Role of TLRs in Obesity and Its Related Metabolic Disorders. International Journal of Molecular Sciences. 2025; 26(5):2229. https://doi.org/10.3390/ijms26052229
https://doi.org/10.3390/ijms26052229
PMid:40076851 PMCid:PMC1190021948. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Investig. 2006; 116:3015-3025. https://doi.org/10.1172/JCI28898
https://doi.org/10.1172/JCI28898
PMid:17053832 PMCid:PMC161619649. Himes RW, Smith CW. Tlr2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J. 2010; 24(3):731-9. https://doi.org/10.1096/fj.09-141929
https://doi.org/10.1096/fj.09-141929
PMid:19841034 PMCid:PMC283013750. Jialal I, Huet BA, Kaur H, Chien A, Devaraj S. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care. 2012; 35(4):900-4. https://doi.org/10.2337/dc11-2375
https://doi.org/10.2337/dc11-2375
PMid:22357188 PMCid:PMC330830751. Lim PS, Chang YK, Wu TK. Serum Lipopolysaccharide-Binding Protein is Associated with Chronic Inflammation and Metabolic Syndrome in Hemodialysis Patients. Blood Purif. 2019; 47:28-36. https://doi.org/10.1159/000492778leber
https://doi.org/10.1159/000492778
PMid:3021981652. Leber B, Tripolt NJ, Blattl D, Eder M, Wascher TC, Pieber TR, et al. The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: An open label, randomized pilot study. Eur J Clin Nutr. 2012; 66:1110-1115. https://doi.org/10.1038/ejcn.2012.103
https://doi.org/10.1038/ejcn.2012.103
PMid:2287203053. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig. 2003; 112:1796-1808. https://doi.org/10.1172/JCI19246
https://doi.org/10.1172/JCI19246
PMid:14679176 PMCid:PMC29699554. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000; 342:836-843. https://doi.org/10.1056/NEJM200003233421202
https://doi.org/10.1056/NEJM200003233421202
PMid:1073337155. Wassmann S, Stumpf M, Strehlow K, Schmid A, Schieffer B, Bohm M, et al. Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor. Circ Res. 2004; 94:534-541. https://doi.org/10.1161/01.RES.0000115557.25127.8D
https://doi.org/10.1161/01.RES.0000115557.25127.8D
PMid:1469901556. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci. 1994; 91:4854-4858. https://doi.org/10.1073/pnas.91.11.4854
https://doi.org/10.1073/pnas.91.11.4854
PMid:8197147 PMCid:PMC4388757. Tchernof A, Bélanger C, Morisset AS, Richard C, Mailloux J, Laberge P, et al. Regional Differences in Adipose Tissue Metabolism in Women: Minor Effect of Obesity and Body Fat Distribution. Diabetes. 2006; 55 (5):1353-1360. https://doi.org/10.2337/db05-1439
https://doi.org/10.2337/db05-1439
PMid:1664469258. Fang L, Guo F, Zhou L, Stahl R, Grams J. The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans. Adipocyte. 2015; 4(4):273-9. https://doi.org/10.1080/21623945.2015.1034920
https://doi.org/10.1080/21623945.2015.1034920
PMid:26451283 PMCid:PMC457319159. Hoffstedt J, Arner E, Wahrenberg H, et al. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia. 2010; 53:2496-2503. https://doi.org/10.1007/s00125-010-1889-3
https://doi.org/10.1007/s00125-010-1889-3
PMid:2083046660. Veilleux A, Caron-Jobin M, Noël S, Laberge PY, Tchernof A. Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes. 2011; 60(5):1504-11. https://doi.org/10.2337/db10-1039
https://doi.org/10.2337/db10-1039
PMid:21421806 PMCid:PMC329232461. McLaughlin T, Lamendola C, Coghlan N, Liu TC, Lerner K, Sherman A, et al. Subcutaneous adipose cell size and distribution: relationship to insulin resistance and body fat. Obesity (Silver Spring). 2014; 22(3):673-80. https://doi.org/10.1002/oby.20209
https://doi.org/10.1002/oby.20209
PMid:23666871 PMCid:PMC434436562. Lönn M, Mehlig K, Bengtsson C, Lissner L. Adipocyte size predicts incidence of type 2 diabetes in women. FASEB J. 2010; 24: 326-331. https://doi.org/10.1096/fj.09-133058
https://doi.org/10.1096/fj.09-133058
PMid:1974117363. Pasarica M, Xie H, Hymel D, et al. Lower total adipocyte number but no evidence for small adipocyte depletion in patients with type 2 diabetes. Diabetes Care. 2009; 32:900-902. https://doi.org/10.2337/dc08-2240
https://doi.org/10.2337/dc08-2240
PMid:19228873 PMCid:PMC267112264. Zand H, Morshedzadeh N, Naghashian F. Signaling pathways linking inflammation to insulin resistance. Diabetes Metab Syndr. 2017; 11(Suppl 1):S307-9.
https://doi.org/10.1016/j.dsx.2017.03.006
PMid:2836522265. Sun, Y, Lin, X, Zou, Z, et al. Association between visceral fat area and metabolic syndrome in individuals with normal body weight: insights from a Chinese health screening dataset. Lipids Health Dis. 2025; 24(57). https://doi.org/10.1186/s12944-025-02482-0
https://doi.org/10.1186/s12944-025-02482-0
PMid:39966964 PMCid:PMC1183764566. Lee A, Kim YJ, Oh SW, Lee CM, Choi HC, Joh HK, et al. Cut-off values for visceral Fat Area identifying Korean adults at risk for metabolic syndrome. Korean J Fam Med. 2018; 39:239-46.
https://doi.org/10.4082/kjfm.17.0099
PMid:29972898 PMCid:PMC605640867. Hayashi T, Boyko EJ, Leonetti DL, McNeely MJ, Newell-Morris L, Kahn SE, et al. Visceral adiposity and the risk of impaired glucose tolerance: a prospective study among Japanese americans. Diabetes Care. 2003; 26:650-5.
https://doi.org/10.2337/diacare.26.3.650
PMid:1261001668. Yang J, Eliasson B, Smith U, Cushman SW. Sherman AS. The Size of Large Adipose Cells Is a Predictor of Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients. Obesity. 2012; 20:932-938. https://doi.org/10.1038/oby.2011.371
https://doi.org/10.1038/oby.2011.371
PMid:22240722 PMCid:PMC345770069. Czerwiec K, Zawrzykraj M, Deptuła M, Skoniecka A, Tymińska A, Zieliński J, et al. Adipose-Derived Mesenchymal Stromal Cells in Basic Research and Clinical Applications. Int J Mol Sci. 2023; 24(4):3888. https://doi.org/10.3390/ijms24043888
https://doi.org/10.3390/ijms24043888
PMid:36835295 PMCid:PMC996263970. Baglioni S, Cantini G, Poli G, Francalanci M, Squecco R, Di Franco A, et al. Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell. PLoS One. 2012; 7(5):e36569. https://doi.org/10.1371/journal.pone.0036569
https://doi.org/10.1371/journal.pone.0036569
PMid:22574183 PMCid:PMC334492471. Yazmín Macotela, Brice Emanuelli, Marcelo A. Mori, Stephane Gesta, Tim J. Schulz, Yu-Hua Tseng, et al. Intrinsic Differences in Adipocyte Precursor Cells From Different White Fat Depots. Diabetes. 2012; 61 (7):1691-1699. https://doi.org/10.2337/db11-1753
https://doi.org/10.2337/db11-1753
PMid:22596050 PMCid:PMC337966572. Qiu G, Zheng G, Ge M, et al. Mesenchymal stem cell‐derived extracellular vesicles affect disease outcomes via transfer of microRNAs. Stem Cell Res Ther. 2018; 9(1):1‐9. https://doi.org/10.1186/s13287-018-1069-9
https://doi.org/10.1186/s13287-018-1069-9
PMid:30463593 PMCid:PMC624982673. Eirin A, Zhu XY, Puranik AS, Woollard JR, Tang H, Dasari S, et al. Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells. PLoS One. 2017; 12(3):e0174303. https://doi.org/10.1371/journal.pone.0174303
https://doi.org/10.1371/journal.pone.0174303
PMid:28333993 PMCid:PMC536391774. Nancarrow-Lei R, Mafi P, Mafi R, Khan W. A systemic review of adult mesenchymal stem cell sources and their multilineage differentiation potential relevant to musculoskeletal tissue repair and regeneration. Curr. Stem Cell Res. Ther. 2017; 12:601-610. https://doi.org/10.2174/1574888X12666170608124303
https://doi.org/10.2174/1574888X12666170608124303
PMid:2859556675. Huang X, Huang L, Lu J, et al. The relationship between telomere length and aging-related diseases. Clin Exp Med. 2025; 25(72). https://doi.org/10.1007/s10238-025-01608-z
https://doi.org/10.1007/s10238-025-01608-z
PMid:40044947 PMCid:PMC1188272376. Oñate B, Vilahur G, Camino‐López S, et al. Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte‐like phenotype. BMC Genomics. 2013; 14(1):625‐637. https://doi.org/10.1186/1471‐2164‐14‐625
https://doi.org/10.1186/1471-2164-14-625
PMid:24040759 PMCid:PMC384866177. Silva KR, Liechocki S, Carneiro JR, et al. Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women. Stem Cell Res Ther. 2015; 6(1):72. https://doi.org/10.1186/s13287-015-0029-x
https://doi.org/10.1186/s13287-015-0029-x
PMid:25884374 PMCid:PMC443552578. Oliva-Olivera W, Lhamyani S, Coin-Araguez L, et al. Neovascular deterioration, impaired NADPH oxidase and inflammatory cytokine expression in adipose-derived multipotent cells from subjects with metabolic syndrome. Metabolism. 2017; 71:132-143. https://doi.org/10.1016/j.metabol.2017.03.012
https://doi.org/10.1016/j.metabol.2017.03.012
PMid:2852186679. Barbagallo I, Li Volti G, Galvano F, Tettamanti G, Pluchinotta FR, Bergante S, et al. Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes. Exp Biol Med (Maywood). 2017; 242(10):1079-1085. https://doi.org/10.1177/1535370216681552
https://doi.org/10.1177/1535370216681552
PMid:27909015 PMCid:PMC544463680. López R, Martí-Chillón GJ, Blanco JF, da Casa C, González-Robledo J, Pescador D, et al. MSCs from polytrauma patients: preliminary comparative study with MSCs from elective-surgery patients. Stem Cell Res Ther. 2021; 12(1):451. https://doi.org/10.1186/s13287-021-02500-9
https://doi.org/10.1186/s13287-021-02500-9
PMid:34380565 PMCid:PMC835642881. Martí-Chillón GJ, Muntión S, Preciado S, Osugui L, Navarro-Bailón A, González-Robledo J, et al. Therapeutic potential of mesenchymal stromal/stem cells in critical-care patients with systemic inflammatory response syndrome. Clin Transl Med. 2023; 13(1):e1163. https://doi.org/10.1002/ctm2.1163
https://doi.org/10.1002/ctm2.1163
PMid:36588089 PMCid:PMC980602082. Gkrinia EMM, Belančić A. The Mechanisms of Chronic Inflammation in Obesity and Potential Therapeutic Strategies: A Narrative Review. Curr Issues Mol Biol. 2025; 47(357). https://doi.org/10.3390/cimb47050357
https://doi.org/10.3390/cimb47050357
PMid:40699756 PMCid:PMC1211070183. Song N, Scholtemeijer MSK. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol Sci. 2020; 41(9):653‐664. https://doi.org/10.1016/j.tips.2020.06.009
https://doi.org/10.1016/j.tips.2020.06.009
PMid:32709406 PMCid:PMC775184484. Müller L, Tunger A, Wobus M, et al. Immunomodulatory properties of mesenchymal stromal cells: an update. Front Cell Dev Biol. 2021; 9:1‐9. https://doi.org/10.3389/fcell.2021.637725
https://doi.org/10.3389/fcell.2021.637725
PMid:33634139 PMCid:PMC790015885. Laroye C, Gibot S, Reppel L, Bensoussan D. Concise review: mesenchymal stromal/stem cells: a new treatment for sepsis and septic shock? Stem Cells. 2017; 35(12):2331‐2339. https://doi.org/10.1002/stem.2695
https://doi.org/10.1002/stem.2695
PMid:2885675986. Huang X, Liu Y, Li Z, Lerman LO. Mesenchymal Stem/Stromal Cells Therapy for Metabolic Syndrome: Potential Clinical Application? Stem Cells. 2023; 41(10):893-906. https://doi.org/10.1093/stmcls/sxad052
https://doi.org/10.1093/stmcls/sxad052
PMid:37407022 PMCid:PMC1056040187. Jiang D, Muschhammer J, Qi Y, Kügler A, de Vries JC, Saffarzadeh M, et al. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells. Stem Cells. 2016; 34(9):2393-406. https://doi.org/10.1002/stem.2417
https://doi.org/10.1002/stem.2417
PMid:27299700 PMCid:PMC557213988. Qi Y, Liu W, Wang X, et al. Adipose-derived mesenchymal stem cells from obese mice prevent body weight gain and hyperglycemia. Stem Cell Res Ther. 2021; 12(1):277. https://doi.org/10.1186/s13287-021-02357-y
https://doi.org/10.1186/s13287-021-02357-y
PMid:33957965 PMCid:PMC810115589. Chen H, Chen X, Zhou Zh, et al. Mesenchymal stromal cell-mediated mitochondrial transfer unveils new frontiers in disease therapy. Stem Cell Res Ther. 2025; 16(546). https://doi.org/10.1186/s13287-025-04675-x
https://doi.org/10.1186/s13287-025-04675-x
PMid:41063290 PMCid:PMC1250585490. Chen G, Fan XY, Zheng XP, Jin YL, Liu Y, Liu SC. Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice. Stem Cell Res Ther. 2020; 11(1):401. https://doi.org/10.1186/s13287-020-01865-7
https://doi.org/10.1186/s13287-020-01865-7
PMid:32938466 PMCid:PMC749387691. Qi Y, Liu W, Wang X, et al. Adipose-derived mesenchymal stem cells from obese mice prevent body weight gain and hyperglycemia. Stem Cell Res Ther. 2021; 12(1):277. https://doi.org/10.1186/s13287-021-02357-y
https://doi.org/10.1186/s13287-021-02357-y
PMid:33957965 PMCid:PMC810115592. Kotikalapudi N, Sampath SJP, Sinha SN, Bhonde R, Mungamuri SK, Venkatesan V. Human placental mesenchymal stromal cell therapy restores the cytokine efflux and insulin signaling in the skeletal muscle of obesity-induced type 2 diabetes rat model. Hum Cell. 2022; 35(2):557-571. https://doi.org/10.1007/s13577-021-00664-3
https://doi.org/10.1007/s13577-021-00664-3
PMid:3509197293. Kotikalapudi N, Sampath SJP, Sinha SN, Bhonde R, Mungamuri SK, Venkatesan V. Placental mesenchymal stem cells restore glucose and energy homeostasis in obesogenic adipocytes. Cell Tissue Res. 2023; 391(1):127-144. https://doi.org/10.1007/s00441-022-03693-y
https://doi.org/10.1007/s00441-022-03693-y
PMid:3622737694. Hu J, Fu Z, Chen Y, et al. Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats. Endocr J. 2015; 62(4):339-352. https://doi.org/10.1507/endocrj.EJ14-0584
https://doi.org/10.1507/endocrj.EJ14-0584
PMid:2573958595. Huang X, Liu Y, Li Z, Lerman LO. Mesenchymal Stem/Stromal Cells Therapy for Metabolic Syndrome: Potential Clinical Application? Stem Cells. 2023; 41(10):893-906. https://doi.org/10.1093/stmcls/sxad052
https://doi.org/10.1093/stmcls/sxad052
PMid:37407022 PMCid:PMC1056040196. Xie Z, Cheng Y, Zhang Q, et al. Anti-obesity effect and mechanism of mesenchymal stem cells influence on obese mice. Open Life Sci. 2021; 16(1):653-666. https://doi.org/10.1515/biol-2021-0061
https://doi.org/10.1515/biol-2021-0061
PMid:34222665 PMCid:PMC823481097. Jaber H, Issa K, Eid A, Saleh FA. The therapeutic effects of adiposederived mesenchymal stem cells on obesity and its associated diseases in diet-induced obese mice. Sci Rep. 2021; 11(1):6291. https://doi.org/10.1038/s41598-021-85917-9
https://doi.org/10.1038/s41598-021-85917-9
PMid:33737713 PMCid:PMC797373898. Domingues CC, Kundu N, Kropotova Y, Ahmadi N, Sen S. Antioxidant‐upregulated mesenchymal stem cells reduce inflammation and improve fatty liver disease in diet‐induced obesity. Stem Cell Res Ther. 2019; 10(1):1‐10. https://doi.org/10.1186/s13287‐019‐1393‐8
https://doi.org/10.1186/s13287-019-1393-8
PMid:31477174 PMCid:PMC672009599. Chow L, Johnson V, Impastato R, Coy J, Strumpf A, Dow S. Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells. Stem Cells Transl Med. 2020; 9(2):235-249. https://doi.org/10.1002/sctm.19-0092
https://doi.org/10.1002/sctm.19-0092
PMid:31702119 PMCid:PMC6988770100. Moeinabadi-Bidgoli K, Rezaee M, Rismanchi H, Mohammadi MM, Babajani A. Mesenchymal stem cell-derived antimicrobial peptides as potential anti-neoplastic agents: new insight into anticancer mechanisms of stem cells and exosomes. Review. Front Cell Dev Biology. 2022; 10. https://doi.org/10.3389/fcell.2022.900418
https://doi.org/10.3389/fcell.2022.900418
PMid:35874827 PMCid:PMC9298847101. Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue‐derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun. 2006; 341(4):1135‐1140. https://doi.org/10.1016/j.bbrc.2006.01.07
https://doi.org/10.1016/j.bbrc.2006.01.072
PMid:16460677102. Lee J, Kim SC, Kim SJ, et al. Differentiation of human adipose tissue‐derived stem cells into aggregates of insulin‐producing cells through the overexpression of pancreatic and duodenal homeobox gene‐1. Cell Transplant. 2013; 22(6):1053‐1060. https://doi.org/10.3727/096368912X657215
https://doi.org/10.3727/096368912X657215
PMid:23031216103. Dave S, Vanikar A, Trivedi H. Ex vivo generation of glucose sensitive insulin secreting mesenchymal stem cells derived from human adipose tissue. Indian J Endocrinol Metab. 2012; 16(7):S65‐S69. https://doi.org/10.4103/2230‐8210.94264
https://doi.org/10.4103/2230-8210.94264
PMid:22701849 PMCid:PMC3354929104. Karaoz E, Okcu A, Ünal ZS, Subasi C, Saglam O, Duruksu G. Adipose tissue‐derived mesenchymal stromal cells efficiently differentiate into insulin‐producing cells in pancreatic islet microenvironment both in vitro and in vivo. Cytotherapy. 2013; 15(5):557‐570. https://doi.org/10.1016/j.jcyt.2013.01.005
https://doi.org/10.1016/j.jcyt.2013.01.005
PMid:23388582105. Huang X, Liu Y, Li Z, Lerman LO. Mesenchymal Stem/Stromal Cells Therapy for Metabolic Syndrome: Potential Clinical Application? Stem Cells. 2023; 41(10):893-906. https://doi.org/10.1093/stmcls/sxad052
https://doi.org/10.1093/stmcls/sxad052
PMid:37407022 PMCid:PMC10560401106. Varghese J, Griffin M, Mosahebi A, Butler P. Systematic review of patient factors affecting adipose stem cell viability and function: implications for regenerative therapy. Stem Cell Res Ther. 2017; 8:45. https://doi.org/10.1186/s13287-017- 0483-8
https://doi.org/10.1186/s13287-017-0483-8
PMid:28241882 PMCid:PMC5329955107. Alicka M, Major P, Wysocki M, Marycz K. Adipose-derived mesenchymal stem cells isolated from patients with type 2 diabetes show reduced “stemness” through an altered secretome profile, impaired anti-oxidative protection, and mitochondrial dynamics deterioration. J Clin Med. 2019; 8(6):765. https://doi.org/10.3390/jcm8060765
https://doi.org/10.3390/jcm8060765
PMid:31151180 PMCid:PMC6617220108. Abu-Shahba N, Mahmoud M, El-Erian AM, et al. Impact of type 2 diabetes mellitus on the immunoregulatory characteristics of adipose tissue-derived mesenchymal stem cells. Int J Biochem Cell Biol. 2021; 140:106072. https://doi.org/10.1016/j.biocel.2021.106072
https://doi.org/10.1016/j.biocel.2021.106072
PMid:34455058
Ivanishchev V, Ustymenko A. Adipose tissue dysfunction under inflammatory conditions and possibilities for its correction using cell therapy. Cell Organ Transpl. 2025; 13(2):e2025132184. doi: 10.22494/cot.v13-2.184

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

