Tissue-Specific Stem Cells

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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†‡§

  1. Hyun Lee1,2,
  2. Jong Kil Lee1,3,
  3. Woo-Kie Min4,
  4. Jae-Hoon Bae5,
  5. Xingxuan He6,
  6. Edward H. Schuchman6,
  7. Jae-sung Bae1,2,¶,*,
  8. Hee Kyung Jin1,3,‖,*

Article first published online: 3 MAR 2010

DOI: 10.1002/stem.401

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 4, pages 821–831, April 2010

Additional Information

How to Cite

Lee, H., Lee, J. K., Min, W.-K., Bae, J.-H., He, X., Schuchman, E. H., Bae, J.-s. and Jin, H. K. (2010), 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. STEM CELLS, 28: 821–831. doi: 10.1002/stem.401

Author Information

  1. 1

    Stem Cell Neuroplasticity Research Group, Daegu, Korea

  2. 2

    Department of Physiology, Cell and Matrix Research Institute, BSEI, World Class University Program, School of Medicine, Daegu, Korea

  3. 3

    Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Daegu, Korea

  4. 4

    Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea

  5. 5

    Department of Physiology, School of Medicine, Keimyung University, Daegu, Korea

  6. 6

    Departments of Genetics and Genomic Sciences & Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, USA

  1. Telephone: +82 53 420 4815; Fax: +82 53 424 3349

  2. ‖

    Telephone: +82 53 950 5966; Fax: +82 53 950 5955

*Kyungpook National University, School of Medicine, 101 Dongindong 2Ga, Jung-Gu, Daegu 700-422, South Korea

  1. †

    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.

  2. ‡

    First published online in STEM CELLS EXPRESS March 3, 2010.

  3. §

    Disclosure of potential conflicts of interest is found at the end of this article.

Publication History

  1. Issue published online: 14 APR 2010
  2. Article first published online: 3 MAR 2010
  3. Manuscript Accepted: 19 FEB 2010
  4. Manuscript Received: 7 DEC 2009

Funded by

  • Ministry of Science and Technology, Republic of Korea
  • Korean Ministry of Education, Science and Technology
  • Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. Grant Number: A084065
  • Ministry of Education, Science and Technology. Grant Number: 2009-0081959

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Keywords:

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

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. STEM CELLS 2010;28:821–83128:821–831

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