Mucopolysaccharidosis enzyme production by bone marrow and dental pulp derived human mesenchymal stem cells
| Autor: | Matilda R. Jackson, Ellenore Martin, Stan Gronthos, Ainslie Derrick Roberts, Nathan Rout-Pitt, Sharon Byers |
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| Přispěvatelé: | Jackson, Matilda, Roberts, Ainslie Derrick, Martin, Ellenore, Rout-Pitt, Nathan, Gronthos, Stan, Byers, Sharon |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cell type
Endocrinology Diabetes and Metabolism Mucopolysaccharidosis Biology Biochemistry Viral vector Glycosaminoglycan Endocrinology Bone Marrow Transduction Genetic Genetics medicine Humans Molecular Biology Cells Cultured Dental Pulp Glucuronidase Glycosaminoglycans Lentivirus Mesenchymal stem cell Mucopolysaccharidosis VII Hematopoietic stem cell Cell Differentiation Mesenchymal Stem Cells Transfection differentiation Mucopolysaccharidoses Hematopoietic Stem Cells medicine.disease hematopoietic stem cells medicine.anatomical_structure Immunology Cancer research Bone marrow mucopolysacchardosis |
| Popis: | Mucopolysaccharidoses (MPS) are inherited metabolic disorders that arise from a complete loss or a reduction in one of eleven specific lysosomal enzymes. MPS children display pathology in multiple cell types leading to tissue and organ failure and early death. Mesenchymal stem cells (MSCs) give rise to many of the cell types affected in MPS, including those that are refractory to current treatment protocols such as hematopoietic stem cell (HSC) based therapy. In this study we compared multiple MPS enzyme production by bone marrow derived (hBM) and dental pulp derived (hDP) MSCs to enzyme production by HSCs. hBM MSCs produce significantly higher levels of MPS I, II, IIIA, IVA, VI and VII enzyme than HSCs, while hDP MSCs produce significantly higher levels of MPS I, IIIA, IVA, VI and VII enzymes. Higher transfection efficiency was observed in MSCs (89%) compared to HSCs (23%) using a lentiviral vector. Over-expression of four different lysosomal enzymes resulted in up to 9303-fold and up to 5559-fold greater levels in MSC cell layer and media respectively. Stable, persistent transduction of MSCs and sustained over-expression of MPS VII enzyme was observed in vitro. Transduction of MSCs did not affect the ability of the cells to differentiate down osteogenic, adipogenic or chondrogenic lineages, but did partially delay differentiation down the non-mesodermal neurogenic lineage. (C) 2015 Elsevier Inc. All rights reserved. usc Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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