UM  > 健康科學學院
Induced pluripotent stem cells for disease modeling and evaluation of therapeutics for niemann-pick disease type A
Long Y.2; Xu M.2; Li R.2; Dai S.2; Beers J.3; Chen G.3; Soheilian F.4; Baxa U.4; Wang M.2; Marugan J.J.2; Muro S.1; Li Z.8; Brady R.7; Zheng W.2
2016-12-01
Source PublicationStem Cells Translational Medicine
ISSN21576580 21576564
Volume5Issue:12Pages:1644-1655
Abstract

Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, γ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development.

KeywordAcid Sphingomyelinase Cyclodextrin Differentiated Neural Stem Cells Induced Pluripotent Stem Cells Niemann-pick Disease Type a Α-tocopherol Δ-tocopherol
DOI10.5966/sctm.2015-0373
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell & Tissue Engineering
WOS IDWOS:000388198200005
Fulltext Access
Citation statistics
Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.University of Maryland
2.National Center for Advancing Translational Sciences
3.National Heart, Lung, and Blood Institute
4.Leidos Inc.
5.Zhejiang University School of Medicine
6.Universidade de Macau
7.National Institute of Neurological Disorders and Stroke
8.Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Long Y.,Xu M.,Li R.,et al. Induced pluripotent stem cells for disease modeling and evaluation of therapeutics for niemann-pick disease type A[J]. Stem Cells Translational Medicine,2016,5(12):1644-1655.
APA Long Y..,Xu M..,Li R..,Dai S..,Beers J..,...&Zheng W..(2016).Induced pluripotent stem cells for disease modeling and evaluation of therapeutics for niemann-pick disease type A.Stem Cells Translational Medicine,5(12),1644-1655.
MLA Long Y.,et al."Induced pluripotent stem cells for disease modeling and evaluation of therapeutics for niemann-pick disease type A".Stem Cells Translational Medicine 5.12(2016):1644-1655.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Long Y.]'s Articles
[Xu M.]'s Articles
[Li R.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Long Y.]'s Articles
[Xu M.]'s Articles
[Li R.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Long Y.]'s Articles
[Xu M.]'s Articles
[Li R.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.