Bone Marrow‐Derived Mesenchymal Stem Cells Prevent the Loss of Niemann‐Pick Type C Mouse Purkinje Neurons by Correcting Sphingolipid Metabolism and Increasing Sphingosine‐1‐phosphate

Niemann‐Pick type C (NP‐C) disease exhibits neuronal sphingolipid storage and cerebellar Purkinje neuron (PN) loss. Although it is clear that PNs are compromised in this disorder, it remains to be defined how neuronal lipid storage causes the PN loss. Our previous studies have shown that bone marrow...

Full description

Saved in:
Bibliographic Details
Published inStem cells (Dayton, Ohio) Vol. 28; no. 4; pp. 821 - 831
Main Authors Lee, Hyun, Lee, Jong Kil, Min, Woo‐Kie, Bae, Jae‐Hoon, He, Xingxuan, Schuchman, Edward H., Bae, Jae‐sung, Jin, Hee Kyung
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2010
Subjects
Animals
Apoptosis
Bone Marrow Cells - cytology
Bone marrow‐derived mesenchymal stem cells
Calcium - metabolism
Cell Differentiation
Cells, Cultured
Coculture Techniques
Lysophospholipids - metabolism
Lysosomes - metabolism
Mesenchymal Stem Cell Transplantation
Mice
Mice, Inbred BALB C
Niemann-Pick Diseases - metabolism
Niemann-Pick Diseases - pathology
Niemann-Pick Diseases - surgery
Niemann‐Pick type C disease model
Purkinje Cells - cytology
Purkinje Cells - metabolism
Purkinje neuron
Sphingosine - analogs & derivatives
Sphingosine - metabolism
Sphingosine‐1‐phosphate
Stem Cells - cytology
Stem Cells - metabolism
Therapeutic potential
Online AccessGet full text

Cover

More Information
Summary:Niemann‐Pick type C (NP‐C) disease exhibits neuronal sphingolipid storage and cerebellar Purkinje neuron (PN) loss. Although it is clear that PNs are compromised in this disorder, it remains to be defined how neuronal lipid storage causes the PN loss. Our previous studies have shown that bone marrow‐derived mesenchymal stem cells (BM‐MSCs) transplantation prevent PN loss in NP‐C mice. The aim of the present study was therefore to examine the neuroprotective mechanism of BM‐MSCs on PNs. We found that NP‐C PNs exhibit abnormal sphingolipid metabolism and defective lysosomal calcium store compared to wild‐type mice PNs. BM‐MSCs promote the survival of NP‐C PNs by correction of the altered calcium homeostasis, restoration of the sphingolipid imbalance, as evidenced by increased sphingosine‐1‐phosphate levels and decreased sphingosine, and ultimately, inhibition of apoptosis pathways. These effects suggest that BM‐MSCs modulate sphingolipid metabolism of endogenous NP‐C PNs, resulting in their survival and improved clinical outcome in mice. STEM CELLS 2010;28:821–83128:821–831
Bibliography:First published online in STEM CELLS
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: J.S.B. D.V.M., Ph.D.: designed all experiments, supervised the project, edited the manuscript; H.K.J. D.V.M., Ph.D.: designed all experiments, supervised the project, edited the manuscript; H.L.: performed the experiments, wrote the manuscript; J.K.L. and W.K.M.: performed the experiments; X.H.: performed lipid analysis; E.H.S.: performed lipid analysis, edited the manuscript; H.L. and J.K.L.: contributed equally to this work; J.H.B.: carried out calcium assay.
EXPRESS
Telephone: +82 53 420 4815; Fax: +82 53 424 3349
March 3, 2010.
Telephone: +82 53 950 5966; Fax: +82 53 950 5955
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.401