Neural cells generated from human induced pluripotent stem cells as a model of CNS involvement in mucopolysaccharidosis type II

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376466" target="_blank" >RIV/00216208:11110/18:10376466 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/18:10376466

Result on the web

<a href="https://doi.org/10.1007/s10545-017-0108-5" target="_blank" >https://doi.org/10.1007/s10545-017-0108-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10545-017-0108-5" target="_blank" >10.1007/s10545-017-0108-5</a>

Result language

angličtina

Original language name

Neural cells generated from human induced pluripotent stem cells as a model of CNS involvement in mucopolysaccharidosis type II

Original language description

Mucopolysaccharidosis type II (MPSII) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene (IDS, Xq28). 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-integrating protocol based on the Sendai virus vector system. We differentiated the iPSC lines into IDS deficient and GAG accumulating beta-Tubulin III+ neurons, GFAP(+) astrocytes, and CNPase(+) 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-derived 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/NV15-33297A" target="_blank" >NV15-33297A: iPS cellular models of X-linked lysosomal disorders with cardiac involvement as a tool for development of novel diagnostic and therapeutic approaches</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Inherited Metabolic Disease

ISSN

0141-8955

e-ISSN

—

Volume of the periodical

41

Issue of the periodical within the volume

2

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

9

Pages from-to

221-229

UT code for WoS article

000426398600008

EID of the result in the Scopus database

2-s2.0-85034627520