{"doi":"10.3389/fcell.2020.00197","title":"Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells","abstract":"Background: Chronic inflammatory conditions such as obesity may adversely impact the biological functions underlying the regenerative potential of mesenchymal stromal/stem cells (MSC). Obesity can impair MSC function by inducing cellular senescence, a growth-arrest program that transitions cells to a pro-inflammatory state. However, the effect of obesity on adipose tissue-derived MSC in human subjects remains unclear. We tested the hypothesis that obesity induces senescence and dysfunction in human MSC. Methods: MSC were harvested from abdominal subcutaneous fat collected from obese and age-matched non-obese subjects (n=40) during bariatric or kidney donation surgeries, respectively. MSC were characterized, their migration and proliferation assessed, and cellular senescence evaluated by gene expression of cell-cycle arrest and senescence-associated secretory phenotype markers. In vitro studies tested MSC effect on injured human umbilical vein endothelial cells (HUVEC). Results: Mean age was 59±8 years, 66% were females. Obese subjects had higher body mass index (BMI) than non-obese. MSC from obese subjects exhibited lower proliferative capacities than non-obese-MSC, suggesting decreased function, whereas their migration remained unchanged. Senescent cell burden and phenotype, manifested as p16, p53, IL-6, and MCP-1 gene expression, were significantly upregulated in obese subjects’ MSC. BMI correlated directly with expression of p16, p21, and IL-6. Furthermore, co-incubation with non-obese, but not with obese MSC, restored VEGF expression that was downregulated in HUVEC. Conclusion: Human obesity triggers an early senescence program and proliferative dysfunction in adipose tissue-derived MSC. Thus, obesity-induced cellular injury may alter efficacy of this endogenous repair system and hamper the feasibility of autologous transplantation in obese individuals.","journal":"Frontiers in Cell and Developmental Biology","year":2020,"id":51003,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":171,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":253557,"name":"LaTonya J. Hickson","orcid":"0000-0002-7485-336X","position":1,"is_corresponding":false},{"id":256714,"name":"Todd A. Kellogg","orcid":null,"position":2,"is_corresponding":false},{"id":253558,"name":"Travis J. McKenzie","orcid":"0000-0002-1343-6941","position":3,"is_corresponding":false},{"id":253559,"name":"Julie K. Heimbach","orcid":"0000-0002-3567-1328","position":4,"is_corresponding":false},{"id":256715,"name":"Timucin Taner","orcid":null,"position":5,"is_corresponding":false},{"id":253560,"name":"Hui Tang","orcid":"0000-0001-8870-6726","position":6,"is_corresponding":false},{"id":256716,"name":"Kyra L. Jordan","orcid":null,"position":7,"is_corresponding":false},{"id":253561,"name":"Ishran M. Saadiq","orcid":"0000-0002-6168-3031","position":8,"is_corresponding":false},{"id":253562,"name":"John R. Woollard","orcid":"0000-0002-3261-7908","position":9,"is_corresponding":false},{"id":253563,"name":"Busra Isik","orcid":"0009-0001-8298-7851","position":10,"is_corresponding":false},{"id":73133,"name":"Mohsen Afarideh","orcid":"0000-0002-3578-5640","position":11,"is_corresponding":false},{"id":106953,"name":"Tamar Tchkonia","orcid":"0000-0003-4623-7145","position":12,"is_corresponding":false},{"id":106952,"name":"James L. Kirkland","orcid":"0000-0003-1676-4905","position":13,"is_corresponding":false},{"id":253564,"name":"Lilach O. Lerman","orcid":"0000-0002-3271-3887","position":14,"is_corresponding":false},{"id":256713,"name":"Sabena M. Conley","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T20:40:28.278215Z","pmid":"32274385","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}