Dying transplanted neural stem cells mediate survival bystander effects in the injured brain

Wei Han, Eva Maria Meißner, Stefanie Neunteibl, Madeline Günther, Jörg Kahnt, Amalia Dolga, Cuicui Xie, Nikolaus Plesnila, Changlian Zhu, Klas Blomgren*, Carsten Culmsee*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)
19 Downloads (Pure)

Samenvatting

Neural stem and progenitor cell (NSPC) transplants provide neuroprotection in models of acute brain injury, but the underlying mechanisms are not fully understood. Here, we provide evidence that caspase-dependent apoptotic cell death of NSPCs is required for sending survival signals to the injured brain. The secretome of dying NSPCs contains heat-stable proteins, which protect neurons against glutamate-induced toxicity and trophic factor withdrawal in vitro, and from ischemic brain damage in vivo. Our findings support a new concept suggesting a bystander effect of apoptotic NSPCs, which actively promote neuronal survival through the release of a protective “farewell” secretome. Similar protective effects by the secretome of apoptotic NSPC were also confirmed in human neural progenitor cells and neural stem cells but not in mouse embryonic fibroblasts (MEF) or human dopaminergic neurons, suggesting that the observed effects are cell type specific and exist for neural progenitor/stem cells across species.

Originele taal-2English
Artikelnummer173
Aantal pagina's11
TijdschriftCell Death and Disease
Volume14
Nummer van het tijdschrift3
DOI's
StatusPublished - mrt.-2023

Citeer dit