A Therapeutic Strategy for Lower Motor Neuron Disease and Injury Integrating Neural Stem Cell Transplantation and Functional Electrical Stimulation in a Rat Model

Int J Mol Sci. 2022 Aug 6;23(15):8760. doi: 10.3390/ijms23158760.

Abstract

Promising treatments for upper motor neuron disease are emerging in which motor function is restored by brain-computer interfaces and functional electrical stimulation. At present, such technologies and procedures are not applicable to lower motor neuron disease. We propose a novel therapeutic strategy for lower motor neuron disease and injury integrating neural stem cell transplantation with our new functional electrical stimulation control system. In a rat sciatic nerve transection model, we transplanted embryonic spinal neural stem cells into the distal stump of the peripheral nerve to reinnervate denervated muscle, and subsequently demonstrated that highly responsive limb movement similar to that of a healthy limb could be attained with a wirelessly powered two-channel neurostimulator that we developed. This unique technology, which can reinnervate and precisely move previously denervated muscles that were unresponsive to electrical stimulation, contributes to improving the condition of patients suffering from intractable diseases of paralysis and traumatic injury.

Keywords: Schwann cells; Wallerian degeneration; cell transplantation; denervated muscle; functional electrical stimulation (FES); muscle reinnervation; neural interface; peripheral nerve injury; regeneration; spinal motor neuron.

MeSH terms

  • Animals
  • Electric Stimulation
  • Motor Neuron Disease* / therapy
  • Motor Neurons / physiology
  • Muscle, Skeletal / innervation
  • Nerve Regeneration / physiology
  • Neural Stem Cells*
  • Rats
  • Rats, Inbred F344
  • Sciatic Nerve / physiology
  • Stem Cell Transplantation