© Matt Hogan
Philip J. Horner, Sean M. Barber, Alvaro Munoz, Houston Methodist Research Institute, Houston, Texas, USA

The effect of FES on synaptic plasticity and integration of IPSC transplants in early chronic cervical SCI

Funded in: 2016, 2017, 2018


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Problem: Stem cell transplantations in chronic SCI have shown only modest functional recovery.

Target: Stem cell therapy in combination with electrical stimulation may enhance the survival and differentiation of stem cell transplants

Goal: This combination may lead to improved functional recovery

 

Those suffering with quadriplegia rate recovery of hand and arm function among the highest treatment priorities. Several studies have documented improvements in functional recovery with stem cell transplantation in acute SCI, but little is known about the role of stem cell transplantation in chronic SCI, which comprises a relatively large portion of the estimated 7.3 million individuals affected by SCI globally. Prior studies examining the benefit of human-induced-pluripotent-stem-cell-neuroprogenitor-cell (hiPSC-NPC) transplantation in models of chronic spinal cord injury have documented only modest functional recovery, but were limited by short follow-up durations and the absence of combinatorial therapies.

Because physiologic neural activity is known to positively influence: (1) neuron survival and differentiation, (2) axonal growth and elongation, and (3) synaptogenesis and dendrite stability, electrical stimulation of the spinal cord after injury may serve to enhance the survival and differentiation of stem cell transplants in SCI while guiding transplanted stem cells to form appropriate connections with surviving host neurons that may lead to improved functional recovery.

Previous attempts by our laboratory to combine electrical stimulation with hiPSC-NPC transplantation were limited by excessive scar formation within the spinal cord related to the placement of penetrating stimulating electrodes within the spinal cord itself. We propose that newly-available surface-based stimulating electrodes could be used instead, evoking functional motor movements in a rat model of chronic cervical SCI without inducing the prohibitive level of glial scarring seen in our prior studies, thus allowing transplanted stem cells to survive, differentiate and facilitate new synaptic connections within and around the area of SCI that allow for improved functional recovery.