Journal
STEM CELLS
Volume 28, Issue 4, Pages 821-831Publisher
WILEY
DOI: 10.1002/stem.401
Keywords
Niemann-Pick type C disease model; Bone marrow-derived mesenchymal stem cells; Purkinje neuron; Sphingosine-1-phosphate; Apoptosis; Therapeutic potential
Categories
Funding
- Ministry of Science and Technology, Republic of Korea [SC4170]
- Korean Ministry of Education, Science and Technology
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A084065]
- Ministry of Education, Science and Technology [2009-0081959]
- Korea Health Promotion Institute [A084065] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2009-0081959, 2009-50379] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
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 wildtype 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;28:821-831
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available