{"doi":"10.1002/jor.25311","title":"In vitro analysis of genome‐engineered muscle‐derived stem cells for autoregulated anti‐inflammatory and antifibrotic activity","abstract":"Traumatic muscle injury leads to chronic and pathologic fibrosis in skeletal muscles, primarily driven through upregulation of transforming growth factor-β1 (TGF-β1). Cell-based therapies, such as injection of muscle-derived stem cells (MDSCs), have shown promise in muscle repair. However, injected MDSCs in injured skeletal muscle can differentiate into myofibroblasts under the influence of TGF-β1, and contribute to the development of fibrosis, limiting their regenerative potential. In this study, we created a \"smart\" cell-based drug delivery system using CRISPR-Cas9 to genetically engineer MDSCs capable of sensing TGF-β1 and producing an antifibrotic biologic, decorin. These gene-edited smart cells, capable of inhibiting fibrosis in a dose-dependent and autoregulating manner, show anti-inflammatory and antifibrotic properties in vitro, without changing the expression of myogenic and stem cell markers as well as their cell proliferation and myogenic differentiation. Additionally, differentiation down a fibrotic lineage is reduced or eliminated in response to TGF-β1. Our results show that gene editing can be used to successfully create smart stem cells capable of producing biologic drugs with antifibrotic capabilities in a controlled and localized manner. This system provides a tool for cell-based drug delivery as the basis for a novel therapeutic approach for a variety of diseases.","journal":"Journal of Orthopaedic Research®","year":2022,"id":277597,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":524035,"name":"Ping Guo","orcid":"0000-0003-1992-7159","position":1,"is_corresponding":false},{"id":524034,"name":"Aiping Lu","orcid":"0000-0001-5529-6599","position":2,"is_corresponding":false},{"id":949651,"name":"Mathew Huard","orcid":null,"position":3,"is_corresponding":false},{"id":232645,"name":"Farshid Guilak","orcid":"0000-0001-7380-0330","position":4,"is_corresponding":false},{"id":287947,"name":"Johnny Huard","orcid":"0000-0002-2926-569X","position":5,"is_corresponding":false},{"id":558706,"name":"Lara Pferdehirt","orcid":"0000-0002-1968-3636","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:28:39.226969Z","pmid":"35293626","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":[]}