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Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP-/- Vim-/- mice.

Journal article
Authors Åsa Widestrand
Jonas Faijerson
Ulrika Wilhelmsson
Peter L P Smith
Lizhen Li
Carina Sihlbom
Peter S Eriksson
Milos Pekny
Published in Stem cells (Dayton, Ohio)
Volume 25
Issue 10
Pages 2619-27
ISSN 1549-4918
Publication year 2007
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 2619-27
Language en
Links dx.doi.org/10.1634/stemcells.2007-0...
Subject categories Neurobiology

Abstract

After neurotrauma, ischemia, or neurodegenerative disease, astrocytes upregulate their expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP), vimentin (Vim), and nestin. This response, reactive gliosis, is attenuated in GFAP(-/-)Vim(-/-) mice, resulting in the promotion of synaptic regeneration after neurotrauma and improved integration of retinal grafts. Here we assessed whether GFAP(-/-)Vim(-/-) astrocytes affect the differentiation of neural progenitor cells. In coculture with GFAP(-/-)Vim(-/-) astrocytes, neural progenitor cells increased neurogenesis by 65% and astrogenesis by 124%. At 35 days after transplantation of neural progenitor cells into the hippocampus, adult GFAP(-/-)Vim(-/-) mice had more transplant-derived neurons and astrocytes than wild-type controls, as well as increased branching of neurite-like processes on transplanted cells. Wnt3 immunoreactivity was readily detected in hippocampal astrocytes in wild-type but not in GFAP(-/-)Vim(-/-) mice. These findings suggest that GFAP(-/-)Vim(-/-) astrocytes allow more neural progenitor cell-derived neurons and astrocytes to survive weeks after transplantation. Thus, reactive gliosis may adversely affect the integration of transplanted neural progenitor cells in the brain. Disclosure of potential conflicts of interest is found at the end of this article.

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