{"doi":"10.1101/2021.03.05.434121","title":"Mesenchymal Stromal Cell Aging Impairs the Self-Organizing Capacity of Lung Alveolar Epithelial Stem Cells","abstract":"Abstract Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form 3-dimentional organoids or “alveolospheres “ with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization, and supports the concept of thermodynamic entropy in aging biology.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217260,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":814068,"name":"Mohammad Rehan","orcid":"0000-0003-3943-2807","position":1,"is_corresponding":false},{"id":814069,"name":"S. Ray Smith","orcid":"0000-0003-1701-4102","position":2,"is_corresponding":false},{"id":667240,"name":"K.G. Dsouza","orcid":null,"position":3,"is_corresponding":false},{"id":272040,"name":"Yong Wang","orcid":"0000-0003-0695-5273","position":4,"is_corresponding":false},{"id":492006,"name":"Karen Bernard","orcid":"0000-0002-7205-1363","position":5,"is_corresponding":false},{"id":814070,"name":"Deepali Kurundkar","orcid":"0000-0001-5223-1431","position":6,"is_corresponding":false},{"id":814678,"name":"Vinayak Memula","orcid":null,"position":7,"is_corresponding":false},{"id":384029,"name":"Kyoko Kojima","orcid":null,"position":8,"is_corresponding":false},{"id":338889,"name":"James A. Mobley","orcid":"0000-0002-3229-7975","position":9,"is_corresponding":false},{"id":242281,"name":"Gloria A. Benavides","orcid":"0000-0002-2640-974X","position":10,"is_corresponding":false},{"id":242291,"name":"Victor Darley‐Usmar","orcid":"0000-0001-8921-7086","position":11,"is_corresponding":false},{"id":442450,"name":"Young-il Kim","orcid":"0000-0001-6806-4551","position":12,"is_corresponding":false},{"id":259117,"name":"Jaroslaw W. Zmijewski","orcid":"0000-0001-7314-6164","position":13,"is_corresponding":false},{"id":228869,"name":"Jessy S. Deshane","orcid":"0000-0002-6761-5662","position":14,"is_corresponding":false},{"id":228870,"name":"Victor J. Thannickal","orcid":"0000-0003-4266-8677","position":15,"is_corresponding":false},{"id":814067,"name":"Diptiman Chanda","orcid":"0000-0002-4835-4460","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:53:20.374789Z","pmid":null,"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":[]}