{"doi":"10.1002/smll.202203725","title":"Human iPSC‐Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System","abstract":"Chronic white adipose tissue (WAT) inflammation has been recognized as a critical early event in the pathogenesis of obesity-related disorders. This process is characterized by the increased residency of proinflammatory M1 macrophages in WAT. However, the lack of an isogenic human macrophage-adipocyte model has limited biological studies and drug discovery efforts, highlighting the need for human stem cell-based approaches. Here, human induced pluripotent stem cell (iPSC) derived macrophages (iMACs) and adipocytes (iADIPOs) are cocultured in a microphysiological system (MPS). iMACs migrate toward and infiltrate into the 3D iADIPOs cluster to form crown-like structures (CLSs)-like morphology around damaged iADIPOs, recreating classic histological features of WAT inflammation seen in obesity. Significantly more CLS-like morphologies formed in aged and palmitic acid-treated iMAC-iADIPO-MPS, showing the ability to mimic inflammatory severity. Importantly, M1 (proinflammatory) but not M2 (tissue repair) iMACs induced insulin resistance and dysregulated lipolysis in iADIPOs. Both RNAseq and cytokines analyses revealed a reciprocal proinflammatory loop in the interactions of M1 iMACs and iADIPOs. This iMAC-iADIPO-MPS thus successfully recreates pathological conditions of chronically inflamed human WAT, opening a door to study the dynamic inflammatory progression and identify clinically relevant therapies.","journal":"Small","year":2023,"id":329184,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":669662,"name":"Koji Matsuo","orcid":"0000-0002-4862-8927","position":1,"is_corresponding":false},{"id":670222,"name":"Ashley Pereira","orcid":null,"position":2,"is_corresponding":false},{"id":777646,"name":"Yue Tung Lee","orcid":null,"position":3,"is_corresponding":false},{"id":1052396,"name":"Fenmiao Zhong","orcid":null,"position":4,"is_corresponding":false},{"id":230911,"name":"Yuchen He","orcid":"0000-0002-3985-7779","position":5,"is_corresponding":false},{"id":284991,"name":"Peter‐James H. Zushin","orcid":"0000-0002-1915-2181","position":6,"is_corresponding":false},{"id":1052397,"name":"Marko Gröger","orcid":null,"position":7,"is_corresponding":false},{"id":348401,"name":"Aditi Sharma","orcid":"0000-0001-7199-0361","position":8,"is_corresponding":false},{"id":556316,"name":"Holger Willenbring","orcid":"0000-0002-7397-2957","position":9,"is_corresponding":false},{"id":416637,"name":"Edward C. Hsiao","orcid":"0000-0001-8924-106X","position":10,"is_corresponding":false},{"id":576823,"name":"Andreas Stahl","orcid":"0000-0002-9096-3024","position":11,"is_corresponding":false},{"id":1051790,"name":"Lin Qi","orcid":"0000-0001-7398-327X","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:09:01.509601Z","pmid":"37104853","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":[]}