{"doi":"10.1101/2021.09.22.461362","title":"Engineered neuron-targeting, placental mesenchymal stromal cell-derived extracellular vesicles for <i>in utero</i> treatment of myelomeningocele","abstract":"ABSTRACT This study investigated the feasibility and efficiency of neuron-targeting hybrid placental mesenchymal stromal cell-derived extracellular vesicles (PMSC-EVs), engineered by membrane fusion with Targeted Axonal Import (TAxI) peptide modified, TrkB agonist 7,8-DHF-loaded liposomes for treatment of myelomeningocele (MMC) via intra-amniotic cavity administration. The prepared TAxI modified liposomes with 7,8-DHF were used to fuse with PMSC-EVs. Different fusion approaches were investigated and freeze-thaw-extrude method was found to be the optimal. The engineered PMSC-EVs had a uniform particle size and efficiently loaded 7,8-DHF. It also had typical markers of native EVs. Freeze-thaw-extrude process did not change the release profile of 7,8-DHF from engineered EVs compared to TAxI modified, 7,8-DHF loaded liposomes. The engineered EVs could elicit TrkB phosphorylation depending on the incorporation of 7,8-DHF while native EVs did not. The engineered EVs increased neurite outgrowth of apoptotic cortical neurons induced by staurosporine, suggesting that they exhibited neuroprotective function. In a rodent model of MMC, neuron-targeting, engineered EVs became an active targeting delivery system to MMC defect sites. Pups treated with engineered EVs had the lowest density of apoptotic cells and displayed a therapeutic outcome. The study suggests the potential use of engineered hybrid, active neuron-targeting EVs for the in utero treatment of MMC.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217902,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"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":0.9516,"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":815219,"name":"Hong‐Yuan Chen","orcid":"0000-0001-5217-668X","position":1,"is_corresponding":false},{"id":363221,"name":"Kewa Gao","orcid":"0000-0002-8781-890X","position":2,"is_corresponding":false},{"id":363222,"name":"Siqi He","orcid":"0000-0002-3601-1938","position":3,"is_corresponding":false},{"id":315456,"name":"Zhao Ma","orcid":"0000-0002-8000-5324","position":4,"is_corresponding":false},{"id":310038,"name":"Ruiwu Liu","orcid":null,"position":5,"is_corresponding":false},{"id":308766,"name":"Dake Hao","orcid":"0000-0002-8533-7344","position":6,"is_corresponding":false},{"id":344282,"name":"Yan Wang","orcid":"0000-0002-7744-4078","position":7,"is_corresponding":false},{"id":401306,"name":"Priyadarsini Kumar","orcid":null,"position":8,"is_corresponding":false},{"id":310037,"name":"Lalithasri Ramasubramanian","orcid":null,"position":9,"is_corresponding":false},{"id":530583,"name":"Christopher D. Pivetti","orcid":"0000-0002-1362-2058","position":10,"is_corresponding":false},{"id":237446,"name":"Yuanpei Li","orcid":"0000-0002-4015-646X","position":11,"is_corresponding":false},{"id":344284,"name":"Fuzheng Guo","orcid":"0000-0003-3410-8389","position":12,"is_corresponding":false},{"id":655284,"name":"Fengshan Wang","orcid":"0000-0002-1182-8597","position":13,"is_corresponding":false},{"id":523577,"name":"Randy P. Carney","orcid":"0000-0001-8193-1664","position":14,"is_corresponding":false},{"id":308767,"name":"Diana L. Farmer","orcid":"0000-0002-3530-5993","position":15,"is_corresponding":false},{"id":259298,"name":"Aijun Wang","orcid":"0000-0002-2985-3627","position":16,"is_corresponding":false},{"id":815218,"name":"Xinke Zhang","orcid":"0000-0002-1215-3296","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:24.683898Z","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":[]}