title: 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.
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.
authors.affiliation: Stem Cell Neuroplasticity Research Group, Daegu, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lee
authors.forename: Jong Kil
authors.initials: JK
authors.lastname: Lee
authors.forename: Woo-Kie
authors.initials: WK
authors.lastname: Min
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Bae
authors.forename: Xingxuan
authors.initials: X
authors.lastname: He
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Bae
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D008246:Lysophospholipids / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D009542:Niemann-Pick Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine; D002118:Calcium