Increased Neurogenesis and Astrogenesis from Neural Progenitor Cells Grafted in the Hippocampus of GFAP super(-/-)Vim super(-/-) Mice

• Published in: Stem cells (Dayton, Ohio) Vol. 25; no. 10; pp. 2619 - 2627
• Main Authors: Widestrand, Aasa, Faijerson, Jonas, Wilhelmsson, Ulrika, Smith, Peter LP, Li, Lizhen, Sihlbom, Carina, Eriksson, Peter S, Pekny, Milos
• Format: Journal Article
• Language: English
• Published: 01.10.2007
• ISSN: 1066-5099

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 super(-/-)Vim super(-/-) mice, resulting in the promotion of synaptic regeneration after neurotrauma and improved integration of retinal grafts. Here we assessed whether GFAP super(-/-)Vim super(-/-) astrocytes affect the differentiation of neural progenitor cells. In coculture with GFAP super(-/-)Vim super(-/-) 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 super(-/-)Vim super(-/-) 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 super(-/-)Vim super(-/-) mice. These findings suggest that GFAP super(-/-)Vim super(-/-) 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.