{"doi":"10.1093/stcltm/szac062","title":"Tanshinone IIA-Loaded Nanoparticle and Neural Stem Cell Therapy Enhances Recovery in a Pig Ischemic Stroke Model","abstract":"Induced pluripotent stem cell-derived neural stem cells (iNSCs) are a multimodal stroke therapeutic that possess neuroprotective, regenerative, and cell replacement capabilities post-ischemia. However, long-term engraftment and efficacy of iNSCs is limited by the cytotoxic microenvironment post-stroke. Tanshinone IIA (Tan IIA) is a therapeutic that demonstrates anti-inflammatory and antioxidative effects in rodent ischemic stroke models and stroke patients. Therefore, pretreatment with Tan IIA may create a microenvironment that is more conducive to the long-term survival of iNSCs. In this study, we evaluated the potential of Tan IIA drug-loaded nanoparticles (Tan IIA-NPs) to improve iNSC engraftment and efficacy, thus potentially leading to enhanced cellular, tissue, and functional recovery in a translational pig ischemic stroke model. Twenty-two pigs underwent middle cerebral artery occlusion (MCAO) and were randomly assigned to a PBS + PBS, PBS + iNSC, or Tan IIA-NP + iNSC treatment group. Magnetic resonance imaging (MRI), modified Rankin Scale neurological evaluation, and immunohistochemistry were performed over a 12-week study period. Immunohistochemistry indicated pretreatment with Tan IIA-NPs increased iNSC survivability. Furthermore, Tan IIA-NPs increased iNSC neuronal differentiation and decreased iNSC reactive astrocyte differentiation. Tan IIA-NP + iNSC treatment enhanced endogenous neuroprotective and regenerative activities by decreasing the intracerebral cellular immune response, preserving endogenous neurons, and increasing neuroblast formation. MRI assessments revealed Tan IIA-NP + iNSC treatment reduced lesion volumes and midline shift. Tissue preservation and recovery corresponded with significant improvements in neurological recovery. This study demonstrated pretreatment with Tan IIA-NPs increased iNSC engraftment, enhanced cellular and tissue recovery, and improved neurological function in a translational pig stroke model.","journal":"Stem Cells Translational Medicine","year":2022,"id":251380,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"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":352682,"name":"Elizabeth S. Waters","orcid":"0000-0002-6106-0360","position":1,"is_corresponding":false},{"id":603228,"name":"Xueyuan Yang","orcid":"0000-0002-1519-6830","position":2,"is_corresponding":false},{"id":493679,"name":"Madison M. Fagan","orcid":"0000-0003-1084-6547","position":3,"is_corresponding":false},{"id":352683,"name":"Kelly M. Scheulin","orcid":"0000-0002-3580-6229","position":4,"is_corresponding":false},{"id":747304,"name":"Sydney E. Sneed","orcid":"0000-0002-4839-9693","position":5,"is_corresponding":false},{"id":894283,"name":"Savannah R. Cheek","orcid":"0000-0002-4060-4154","position":6,"is_corresponding":false},{"id":352679,"name":"Julie Jeon","orcid":"0000-0002-6862-144X","position":7,"is_corresponding":false},{"id":494686,"name":"Soo K. Shin","orcid":null,"position":8,"is_corresponding":false},{"id":352685,"name":"Holly A. Kinder","orcid":"0000-0001-8310-7265","position":9,"is_corresponding":false},{"id":894284,"name":"Anil Kumar","orcid":"0000-0001-6813-7765","position":10,"is_corresponding":false},{"id":352686,"name":"Simon R. Platt","orcid":"0000-0002-7818-1011","position":11,"is_corresponding":false},{"id":494687,"name":"Kylee J. Duberstein","orcid":null,"position":12,"is_corresponding":false},{"id":352690,"name":"Hea Jin Park","orcid":"0000-0002-1611-1077","position":13,"is_corresponding":false},{"id":352634,"name":"Jin Xie","orcid":"0000-0002-8915-6233","position":14,"is_corresponding":false},{"id":352689,"name":"Franklin D. West","orcid":"0000-0002-0504-7997","position":15,"is_corresponding":false},{"id":352681,"name":"Erin E. Kaiser","orcid":"0000-0003-1521-950X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:24:37.429628Z","pmid":"36124817","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":[]}