ArticleStem cell research & therapy2021
Umbilical mesenchymal stem cell-derived extracellular vesicles as enzyme delivery vehicle to treat Morquio A fibroblasts.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- From Uptake to Therapeutic Function in Engineered Exosome Delivery Systems.Research (Washington, D.C.) · 2026Review
- Recent advances in mucopolysaccharidosis IVA treatment.Orphanet journal of rare diseases · 2025Review
- Mesenchymal Stem Cell-Derived Extracellular Vesicles: Seeking into Cell-Free Therapies for Bone-Affected Lysosomal Storage Disorders.International journal of molecular sciences · 2025Review
- Exploring the potential of bacterial-derived EVs for targeted enzyme replacement therapy: mechanisms, applications, and future directions.Archives of microbiology · 2025Review
- Extracellular Vesicles as Tools for Crossing the Blood-Brain Barrier to Treat Lysosomal Storage Diseases.Life (Basel, Switzerland) · 2025Review
- Amelioration of Inflammation and Metabolic Blockage in GALC Deficient Mice After Enzyme Replacement Therapy via Extracellular Vesicles.International journal of nanomedicine · 2025Article
- Evidence of Lysosomal β-Hexosaminidase Enzymatic Activity Associated with Extracellular Vesicles: Potential Applications for the Correction of Sandhoff Disease.Journal of functional biomaterials · 2024Article
- Mesenchymal Stem Cell-Derived Exosomes in Ophthalmology: A Comprehensive Review.Pharmaceutics · 2023Review
- Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.Frontiers in cell and developmental biology · 2023Review
- A kaleidoscopic view of extracellular vesicles in lysosomal storage disorders.Extracellular vesicles and circulating nucleic acids · 2022Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMucopolysaccharidosis IVA (Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which results in the accumulation of the glycosaminoglycans (GAGs), keratan sulfate, and chondroitin-6-sulfate in the lysosomes of all tissues causing systemic dysfunction. Current treatments include enzyme replacement therapy (ERT) which can treat only certain aspects of the disease such as endurance-related biological endpoints. A key challenge in ERT is ineffective enzyme uptake in avascular tissues, which makes the treatment of the corneal, cartilage, and heart valvular tissue difficult. The aim of this study was to culture human umbilical mesenchymal stem cells (UMSC), demonstrate presence of GALNS enzyme activity within the extracellular vesicles (EVs) derived from these UMSC, and study how these secreted EVs are taken up by GALNS-deficient cells and used by the deficient cell's lysosomes.
methodsWe obtained and cultured UMSC from the umbilical cord tissue from anonymous donors from the Saint Louis Cord Blood Bank. We characterized UMSC cell surface markers to confirm phenotype by cell sorting analyses. In addition, we confirmed that UMSC secrete GALNS enzyme creating conditioned media for co-culture experiments with GALNS deficient cells. Lastly, we isolated EVs derived from UMSC by ultracentrifugation to confirm source of GALNS enzyme.
resultsCo-culture and confocal microscopy experiments indicated that the lysosomal content from UMSC migrated to deficient cells as evidenced by the peak signal intensity occurring at 15 min. EVs released by UMSC were characterized indicating that the EVs contained the active GALNS enzyme. Uptake of GALNS within EVs by deficient fibroblasts was not affected by mannose-6-phosphate (M6P) inhibition, suggesting that EV uptake by these fibroblasts is gradual and might be mediated by a different means than the M6P receptor.
conclusionsUMSC can deliver EVs containing functional GALNS enzyme to deficient cells. This enzyme delivery method, which was unaffected by M6P inhibition, can function as a novel technique for reducing GAG accumulation in cells in avascular tissues, thereby providing a potential treatment option for Morquio A syndrome.
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