Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Cell Death Dis. 2023 Mar 1;14(3):173. doi: 10.1038/s41419-023-05698-z.
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.
神经干细胞和祖细胞 (NSPC) 移植为急性脑损伤模型提供了神经保护作用，但潜在的机制尚不完全清楚。在这里，我们提供的证据表明，NSPC 细胞的 caspase 依赖性凋亡是向受损大脑发送存活信号所必需的。垂死 NSPC 的分泌组含有热稳定蛋白，这些蛋白可以保护神经元免受体外谷氨酸诱导的毒性和营养因子缺失的影响，以及体内缺血性脑损伤的影响。我们的研究结果支持了一个新的概念，即凋亡 NSPC 的旁观者效应，通过释放保护性的“告别”分泌组，凋亡 NSPC 可以主动促进神经元存活。凋亡 NSPC 的分泌组在人神经祖细胞和神经干细胞中也证实了类似的保护作用，但在小鼠胚胎成纤维细胞 (MEF) 或人多巴胺能神经元中没有证实，这表明观察到的作用是细胞类型特异性的，并且在跨物种的神经祖细胞/干细胞中存在。
