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Attenuation of reactive gliosis in stroke-injured mouse brain does not affect neurogenesis from grafted human iPSC-derived neural progenitors

Journal article
Authors C. Laterza
N. Uoshima
D. Tornero
Ulrika Wilhelmsson
Anna Stokowska
R. M. Ge
Milos Pekny
O. Lindvall
Z. Kokaia
Published in Plos One
Volume 13
Issue 2
ISSN 1932-6203
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Language en
Keywords fibrillary acidic protein, central-nervous-system, stem-cells, astrocyte, activation, ischemic-stroke, cortical-neurons, mice deficient, dentate, gyrus, human cns, vimentin, Science & Technology - Other Topics, ates of america, v103, p17513
Subject categories Neurosciences


Induced pluripotent stem cells (iPSCs) or their progeny, derived from human somatic cells, can give rise to functional improvements after intracerebral transplantation in animal models of stroke. Previous studies have indicated that reactive gliosis, which is associated with stroke, inhibits neurogenesis from both endogenous and grafted neural stem/progenitor cells (NSPCs) of rodent origin. Here we have assessed whether reactive astrocytes affect the fate of human iPSC-derived NSPCs transplanted into stroke-injured brain. Mice with genetically attenuated reactive gliosis (deficient for GFAP and vimentin) were subjected to cortical stroke and cells were implanted adjacent to the ischemic lesion one week later. At 8 weeks after transplantation, immunohistochemical analysis showed that attenuated reactive gliosis did not affect neurogenesis or commitment towards glial lineage of the grafted NSPCs. Our findings, obtained in a human-to-mouse xenograft experiment, provide evidence that the reactive gliosis in stroke-injured brain does not affect the formation of new neurons from intracortically grafted human iPSC-derived NSPCs. However, for a potential clinical translation of these cells in stroke, it will be important to clarify whether the lack of effect of reactive gliosis on neurogenesis is observed also in a human-to-human experimental setting.

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