Electroacupuncture Facilitates the Integration of Neural Stem Cell-Derived Neural Network with Transected Rat Spinal Cord

Abstract

Summary: The hostile environment of an injured spinal cord makes it challenging to achieve higher viability in a grafted tissue-engineered neural network used to reconstruct the spinal cord circuit. Here, we investigate whether cell survival and synaptic transmission within an NT-3 and TRKC gene-overexpressing neural stem cell-derived neural network scaffold (NN) transplanted into transected spinal cord could be promoted by electroacupuncture (EA) through improving the microenvironment. Our results showed that EA facilitated the cell survival, neuronal differentiation, and synapse formation of a transplanted NN. Pseudorabies virus tracing demonstrated that EA strengthened synaptic integration of the transplanted NN with the host neural circuit. The combination therapy also promoted axonal regeneration, spinal conductivity, and functional recovery. The findings highlight EA as a potential and safe supplementary therapeutic strategy to reinforce the survival and synaptogenesis of a transplanted NN as a neuronal relay to bridge the two severed ends of an injured spinal cord. : In this article, Y.S. Zeng, Y. Ding, and colleagues show that EA treatment can reinforce the survival, neuronal differentiation, and synaptic connections of donor neurons in injured spinal cord by activating the NT-3/TRKC/AKT pathway. Moreover, the combinational therapy fosters host axonal regeneration into the injury/graft site to rebuild the synaptic connections with grafted NN, and improves nerve conduction of the spinal cord as well as locomotor function of paralyzed hindlimbs. Keywords: spinal cord injury, electroacupuncture, neural stem cells, tissue-engineered neural network, neurotrophin-3, neuronal relay