{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:11:40Z","timestamp":1790820700643,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Medical Research Agency of The Czech Republic","award":["AZV \u010cR 15-33297A"],"award-info":[{"award-number":["AZV \u010cR 15-33297A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis type II (MPSII) is a rare X\u2010linked lysosomal storage disorder caused by mutations in the iduronate\u20102\u2010sulfatase (IDS) gene (<jats:italic>IDS, Xq28<\/jats:italic>). MPSII is characterized by skeletal deformities, hearing loss, airway obstruction, hepatosplenomegaly, cardiac valvular disease, and progressive neurological impairment. At the cellular level, IDS deficiency leads to lysosomal storage of glycosaminoglycans (GAGs), dominated by accumulation of dermatan and heparan sulfates. Human induced pluripotent stem cells (iPSC) represent an alternative system that complements the available MPSII murine model. Herein we report on the reprogramming of peripheral white blood cells from male and female MPSII patients into iPSC using a non\u2010integrating protocol based on the Sendai virus vector system. We differentiated the iPSC lines into IDS deficient and GAG accumulating \u03b2\u2010Tubulin III<jats:sup>+<\/jats:sup> neurons, GFAP<jats:sup>+<\/jats:sup> astrocytes, and CNPase<jats:sup>+<\/jats:sup> oligodendrocytes. The lysosomal system in these cells displayed structural abnormalities reminiscent of those previously found in patient tissues and murine IDS deficient neuronal stem cells. Furthermore, quantitative determination of GAGs revealed a moderate increase in GAG levels in IDS deficient neurons and glia. We also tested the effects of recombinant IDS and found that the exogenous enzyme was internalized from the culture media and partially decreased the intracellular GAG levels in iPSC\u2010derived neural cells; however, it failed to completely prevent accumulation of GAGs. In summary, we demonstrate that this human iPSC based model expresses the cellular and biochemical features of MPSII, and thus represents a useful experimental tool for further pathogenesis studies as well as therapy development and testing.<\/jats:p>","DOI":"10.1007\/s10545-017-0108-5","type":"journal-article","created":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T20:08:21Z","timestamp":1511381301000},"page":"221-229","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Neural cells generated from human induced pluripotent stem cells as a model of CNS involvement in mucopolysaccharidosis type II"],"prefix":"10.1002","volume":"41","author":[{"given":"Jitka","family":"Rybov\u00e1","sequence":"first","affiliation":[{"name":"Rare Diseases Research Unit, Department of Pediatrics and Adolescent Medicine Charles University Ke Karlovu 2 Prague 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Ledvinov\u00e1","sequence":"additional","affiliation":[{"name":"Rare Diseases Research Unit, Department of Pediatrics and Adolescent Medicine Charles University Ke Karlovu 2 Prague 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Sikora","sequence":"additional","affiliation":[{"name":"Rare Diseases Research Unit, Department of Pediatrics and Adolescent Medicine Charles University Ke Karlovu 2 Prague 12808 Czech Republic"},{"name":"Institute of Pathology, First Faculty of Medicine Charles University and General University Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Kucha\u0159","sequence":"additional","affiliation":[{"name":"Rare Diseases Research Unit, Department of Pediatrics and Adolescent Medicine Charles University Ke Karlovu 2 Prague 12808 Czech 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