Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis

Sci Transl Med 19 December 2012:
Vol. 4, Issue 165, p. 165ra164
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004579

• Research Article

Stem Cells

Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis

1. Yang D. Teng¹,²,³,*,†,


2. Susanna C. Benn⁴,*,


3. Steven N. Kalkanis¹,⁴,


4. Jeremy M. Shefner⁵,


5. Renna C. Onario¹,²,³,


6. Bin Cheng⁶,


7. Mahesh B. Lachyankar³,


8. Michael Marconi³,⁷,


9. Jianxue Li⁷,


10. Dou Yu¹,²,


11. Inbo Han¹,²,


12. Nicholas J. Maragakis⁸,


13. Jeronia Lládo⁸,


14. Kadir Erkmen¹,³,


15. D. Eugene Redmond Jr.⁹,


16. Richard L. Sidman¹,⁷,


17. Serge Przedborski¹⁰,


18. Jeffrey D. Rothstein⁸,


19. Robert H. Brown Jr.⁴,¹¹,† and


20. Evan Y. Snyder¹,³,⁷,¹²,†

+ Author Affiliations

1. 
   ¹Departments of Neurosurgery and PM&R, Brigham & Women’s Hospital, Spaulding Rehabilitation Hospital and Harvard Medical School, Boston, MA 02115, USA.
   
   


2. 
   ²SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA 02132, USA.
   
   


3. 
   ³Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
   
   


4. 
   ⁴Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
   
   


5. 
   ⁵Department of Neurology, State University of New York, Syracuse, NY 13210, USA.
   
   


6. 
   ⁶Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
   
   


7. 
   ⁷Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
   
   


8. 
   ⁸Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
   
   


9. 
   ⁹Department of Psychiatry and Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
   
   


10. 
    ¹⁰Movement Disorder Division, Neurological Institute, Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
    
    


11. 
    ¹¹Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
    
    


12. 
    ¹²Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
    
    

+ Author Notes

• 
  ↵* These authors contributed equally to this work.
  
  

1. ↵†To whom correspondence may be addressed. E-mail: esnyder@sanfordburnham.org (E.Y.S.); Robert.Brown@umassmed.edu (R.H.B.); yang_teng@hms.harvard.edu (Y.D.T.)

Abstract

Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by the unremitting degeneration of motor neurons. Multiple processes involving motor neurons and other cell types have been implicated in its pathogenesis. Neural stem cells (NSCs) perform multiple actions within the nervous system to fulfill their functions of organogenesis and homeostasis. We test the hypothesis that transplanted, undifferentiated multipotent migratory NSCs may help to ameliorate an array of pathological mechanisms in the SOD1^G93A transgenic mouse model of ALS. On the basis of a meta-analysis of 11 independent studies performed by a consortium of ALS investigators, we propose that transplanted NSCs (both mouse and human) can slow both the onset and the progression of clinical signs and prolong survival in ALS mice, particularly if regions sustaining vital functions such as respiration are rendered chimeric. The beneficial effects of transplanted NSCs seem to be mediated by a number of actions including their ability to produce trophic factors, preserve neuromuscular function, and reduce astrogliosis and inflammation. We conclude that the widespread, pleiotropic, modulatory actions exerted by transplanted NSCs may represent an accessible therapeutic application of stem cells for treating ALS and other untreatable degenerative diseases.

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

Citation: Y. D. Teng, S. C. Benn, S. N. Kalkanis, J. M. Shefner, R. C. Onario, B. Cheng, M. B. Lachyankar, M. Marconi, J. Li, D. Yu, I. Han, N. J. Maragakis, J. Lládo, K. Erkmen, D. E. Redmond, R. L. Sidman, S. Przedborski, J. D. Rothstein, R. H. Brown, E. Y. Snyder, Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis. Sci. Transl. Med. 4, 165ra164 (2012).

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