Open AccessBone 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
Author(s) -
Lee Hyun,
Lee Jong Kil,
Min WooKie,
Bae JaeHoon,
He Xingxuan,
Schuchman Edward H.,
Bae Jaesung,
Jin Hee Kyung
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.401
Subject(s) - sphingolipid , biology , sphingosine , mesenchymal stem cell , sphingosine 1 phosphate , microbiology and biotechnology , bone marrow , stem cell , calcium , medicine , biochemistry , immunology , receptor
Abstract 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. S TEM C ELLS 2010;28:821–83128:821–831