Bcl-xL Promotes the Survival of Motor Neurons Derived from Neural Stem Cells

SIMPLE SUMMARY: Neural stem cells (NSCs) are used for developing cellular replacement strategies for motor neuron diseases. However, this approach has been limited by poor survival and the insufficient function of NSC-derived motor neurons. Seeking to overcome these challenges, we generated pro-survival and drug-inducible NSCs, called NILB-mNSCs, which limited the neuronal death of motor neurons in a medium with doxycycline in vitro. The data obtained indicate that the special genetic modification of NSCs will be helpful for survival and the formation of motor neurons. ABSTRACT: Neural stem cell (NSC) transplantation creates new hope for the treatment of neurodegenerative disorders by direct differentiation into neurons. However, this technique is limited by poor survival and functional neuron deficiency. In this research study, we generated pro-survival murine NSCs (mNSCs) via the ectopic expression of Bcl-xL. A doxycycline (Dox)-inducible Ngn2-Isl1-Lhx3 system was also integrated into the mNSC genome. The four gene-modified mNSCs can rapidly and effectively differentiate into motor neurons after Dox treatments. Ectopic Bcl-xL could resist replating-induced stress, glutamate toxicity, neuronal apoptosis and remarkably promote the survival of motor neurons. Taken together, we established genetically modified mNSCs with improved survival, which may be useful for motor neuron degenerative diseases.