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
- Yang D. Teng1,2,3,*,†,
- Susanna C. Benn4,*,
- Steven N. Kalkanis1,4,
- Jeremy M. Shefner5,
- Renna C. Onario1,2,3,
- Bin Cheng6,
- Mahesh B. Lachyankar3,
- Michael Marconi3,7,
- Jianxue Li7,
- Dou Yu1,2,
- Inbo Han1,2,
- Nicholas J. Maragakis8,
- Jeronia Lládo8,
- Kadir Erkmen1,3,
- D. Eugene Redmond Jr.9,
- Richard L. Sidman1,7,
- Serge Przedborski10,
- Jeffrey D. Rothstein8,
- Robert H. Brown Jr.4,11,† and
- Evan Y. Snyder1,3,7,12,†
+ Author Affiliations
- ↵†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.
- Copyright © 2012, American Association for the Advancement of Science
Citation: 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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