Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting

神经干细胞移植引发的早期先天免疫反应的时空演变

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作者:Kristien Reekmans, Nathalie De Vocht, Jelle Praet, Erik Fransen, Debbie Le Blon, Chloé Hoornaert, Jasmijn Daans, Herman Goossens, Annemie Van der Linden, Zwi Berneman, Peter Ponsaerts

Conclusions

The present study quantitatively describes the early post-transplantation events following NSC grafting in the adult mouse brain and warrants that such intervention is directly associated with a high degree of cell loss, subsequently followed by strong glial cell responses.

Methods

Here, we applied in vivo bioluminescence imaging (BLI) and post-mortem quantitative histological analysis to determine the localisation and survival of grafted NSCs at early time points post-transplantation.

Results

An initial dramatic cell loss (up to 80% of grafted cells) due to apoptosis could be observed within the first 24 hours post-implantation, coinciding with a highly hypoxic NSC graft environment. Subsequently, strong spatiotemporal microglial and astroglial cell responses were initiated, which stabilised by day 5 post-implantation and remained present during the whole observation period. Moreover, the increase in astrocyte density was associated with a high degree of astroglial scarring within and surrounding the graft site. During the two-week follow up in this study, the NSC graft site underwent extensive remodelling with NSC graft survival further declining to around 1% of the initial number of grafted cells. Conclusions: The present study quantitatively describes the early post-transplantation events following NSC grafting in the adult mouse brain and warrants that such intervention is directly associated with a high degree of cell loss, subsequently followed by strong glial cell responses.

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