{"doi":"10.1177/09636897251323966","title":"Transplantation of Wild-Type Hematopoietic Stem and Progenitor Cells Improves Disease Phenotypes in a Mucopolysaccharidosis IIIC Mouse Model","abstract":"Mucopolysaccharidosis type IIIC (MPS IIIC) is a severe neurodegenerative lysosomal storage disease caused by the loss-of-function of the lysosomal transmembrane protein acetyl-CoA: heparan-α-glucosamine N -acetyltransferase. MPS IIIC is characterized by the accumulation of the glycosaminoglycan (GAG) heparan sulfate. There is no treatment for this disease. We generated a new MPS IIIC mouse model and confirmed disease phenotypes such as GAG accumulation, splenomegaly, neurological defects, and presence of disease-specific non-reducing end carbohydrates. To explore a new therapeutic strategy for this condition, we transplanted wild-type (WT) hematopoietic stem and progenitor cells (HSPCs) into lethally irradiated 2-month-old Hgsnat −/− mice and analyzed the resulting impact 6 months later. Transplanted HSPCs differentiated into macrophages in tissues and microglia-like cells in the brain. This resulted in a partial restoration of Hgsnat expression and enzymatic activity along with a significant reduction of the MPS IIIC-specific non-reducing end carbohydrate in the treated Hgsnat −/− mice compared to untreated Hgsnat −/− mice or Hgsnat −/− mice transplanted with Hgsnat −/− HPSCs. In addition, WT HSPC transplant resulted in improved neurological defects, reduction in splenomegaly, and urine retention in the Hgsnat −/− mice. Furthermore, presence of glomerular hyaline bodies with focal fibrosis and sclerosis was observed in the kidney of the disease controls, whereas these abnormalities were improved in the Hgsnat −/− mice treated with WT HSPCs. These data support that HSPC transplantation presents a promising therapeutic avenue for MPS IIIC and represents the first step toward the clinical translation of an HSPC-mediated therapy strategy for MPS IIIC.","journal":"Cell Transplantation","year":2025,"id":550353,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9458,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1445959,"name":"Kasra Pakravesh","orcid":null,"position":1,"is_corresponding":false},{"id":14125,"name":"Kevin Thai","orcid":"0009-0001-9142-1243","position":2,"is_corresponding":false},{"id":1445960,"name":"Frankie Son","orcid":null,"position":3,"is_corresponding":false},{"id":1445612,"name":"Rola Chen","orcid":"0009-0007-7309-2072","position":4,"is_corresponding":false},{"id":473568,"name":"Joseph Rainaldi","orcid":"0000-0003-4123-0008","position":5,"is_corresponding":false},{"id":1445961,"name":"Kalvin Duong","orcid":null,"position":6,"is_corresponding":false},{"id":1445962,"name":"Pauline Losay","orcid":null,"position":7,"is_corresponding":false},{"id":889538,"name":"Anusha Sivakumar","orcid":"0000-0002-1366-9681","position":8,"is_corresponding":false},{"id":1227947,"name":"Veenita Khare","orcid":null,"position":9,"is_corresponding":false},{"id":1445963,"name":"Alexis N. Corl","orcid":null,"position":10,"is_corresponding":false},{"id":1445964,"name":"Rushil Pithia","orcid":null,"position":11,"is_corresponding":false},{"id":715520,"name":"Christine Tran","orcid":"0000-0003-4373-0444","position":12,"is_corresponding":false},{"id":1179890,"name":"J.D. Esko","orcid":null,"position":13,"is_corresponding":false},{"id":473571,"name":"Stéphanie Cherqui","orcid":"0000-0003-1240-5219","position":14,"is_corresponding":false},{"id":1227382,"name":"Rafael A. Badell‐Grau","orcid":"0000-0001-7640-822X","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:54:16.596730Z","pmid":"40126917","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":[]}