jueves, 20 de diciembre de 2012

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

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


Sci Transl Med
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. 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 SOD1G93A 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.






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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