Ischemic and hemorrhagic stroke lesion environments differentially alter the glia repair potential of neural progenitor cell and immature astrocyte grafts.

Autor: Adewumi HO; Department of Biomedical Engineering, Boston University, Boston, MA 02215-2407, USA., Berniac GI; Department of Biomedical Engineering, Boston University, Boston, MA 02215-2407, USA., McCarthy EA; Department of Biomedical Engineering, Boston University, Boston, MA 02215-2407, USA., O'Shea TM; Department of Biomedical Engineering, Boston University, Boston, MA 02215-2407, USA. Electronic address: toshea@bu.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Apr; Vol. 374, pp. 114692. Date of Electronic Publication: 2024 Jan 18.
DOI: 10.1016/j.expneurol.2024.114692
Abstrakt: Using cell grafting to direct glia-based repair mechanisms in adult CNS injuries represents a potential therapeutic strategy for supporting functional neural parenchymal repair. However, glia repair directed by neural progenitor cell (NPC) grafts is dramatically altered by increasing lesion size, severity, and mode of injury. To address this, we studied the interplay between astrocyte differentiation and cell proliferation of NPC in vitro to generate proliferating immature astrocytes (ImA) using hysteretic conditioning. ImA maintain proliferation rates at comparable levels to NPC but showed robust immature astrocyte marker expression including Gfap and Vimentin. ImA demonstrated enhanced resistance to myofibroblast-like phenotypic transformations upon exposure to serum enriched environments in vitro compared to NPC and were more effective at scratch wound closure in vitro compared to quiescent astrocytes. Glia repair directed by ImA at acute ischemic striatal stroke lesions was equivalent to NPC but better than quiescent astrocyte grafts. While ischemic injury environments supported enhanced survival of grafts compared to healthy striatum, hemorrhagic lesions were hostile towards both NPC and ImA grafts leading to poor survival and ineffective modulation of natural wound repair processes. Our findings demonstrate that lesion environments, rather than transcriptional pre-graft states, determine the survival, cell-fate, and glia repair competency of cell grafts applied to acute CNS injuries.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Timothy Mark O'Shea reports financial support was provided by Craig H. Neilsen Foundation. Honour Adewumi reports was provided by Faculty for the Future from Schlumberger Foundation. Editor for Experimental Neurology, Timothy Mark O'Shea.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: