Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination


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> Uchida et al., 4:(155): 155ra136

Sci Transl Med 10 October 2012:
Vol. 4, Issue 155, p. 155ra136
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004371

Research Article  STEM CELLS

Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination

1. Nobuko Uchida¹,*,
2. Kevin Chen²,
3. Monika Dohse¹,
4. Kelly D. Hansen²,
5. Justin Dean²,
6. Joshua R. Buser²,
7. Art Riddle²,
8. Douglas J. Beardsley²,
9. Ying Wan²,
10. Xi Gong²,
11. Thuan Nguyen³,
12. Brian J. Cummings⁴,
13. Aileen J. Anderson⁴,
14. Stanley J. Tamaki¹,
15. Ann Tsukamoto¹,
16. Irving L. Weissman⁵,
17. Steven G. Matsumoto⁶,
18. Larry S. Sherman⁶,
19. Christopher D. Kroenke⁷,⁸ and
20. Stephen A. Back²,⁹,*

+ Author Affiliations

1. ¹StemCells Inc., Newark, CA 94560, USA.
2. ²Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239–3098, USA.
3. ³Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR 97239–3098, USA.
4. ⁴Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697–1705, USA.
5. ⁵Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, CA 94305, USA.
6. ⁶Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
7. ⁷Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239–3098, USA.
8. ⁸Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239–3098, USA.
9. ⁹Department of Neurology, Oregon Health & Science University, Portland, OR 97239–3098, USA.

1. ↵*To whom correspondence should be addressed. E-mail: nobuko.uchida@stemcellsinc.com (N.U.); backs@ohsu.edu (S.A.B.)

Abstract



Shiverer-immunodeficient (Shi-id) mice demonstrate defective myelination in the central nervous system (CNS) and significant ataxia by 2 to 3 weeks of life.

Expanded, banked human neural stem cells (HuCNS-SCs) were transplanted into three sites in the brains of neonatal or juvenile Shi-id mice, which were asymptomatic or showed advanced hypomyelination, respectively. 

In both groups of mice, HuCNS-SCs engrafted and underwent preferential differentiation into oligodendrocytes. 

These oligodendrocytes generated compact myelin with normalized nodal organization, ultrastructure, and axon conduction velocities. 

Myelination was equivalent in neonatal and juvenile mice by quantitative histopathology and high-field ex vivo magnetic resonance imaging, which, through fractional anisotropy, revealed CNS myelination 5 to 7 weeks after HuCNS-SC transplantation. 

Transplanted HuCNS-SCs generated functional myelin in the CNS, even in animals with severe symptomatic hypomyelination, suggesting that this strategy may be useful for treating dysmyelinating diseases.

• Copyright © 2012, American Association for the Advancement of Science

Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination. Sci. Transl. Med. 4, 155ra136 (2012).

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 Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination

 Link: http://stm.sciencemag.org/content/4/155/155ra136