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

Hyun Lee, Jong Kil Lee, Woo Kie Min, Jae Hoon Bae, Xingxuan He, Edward H. Schuchman, Jae Sung Bae, Hee Kyung Jin

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)821-831
Number of pages11
JournalStem Cells
Volume28
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • Apoptosis
  • Bone marrow-derived mesenchymal stem cells
  • Niemann-pick type C disease model
  • Purkinje neuron
  • Sphingosine-1-phosphate
  • Therapeutic potential

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