Phil Horner / Matthew Hogan, Houston Methodist Research Institute, Center for Neuroregeneration, Houston, USA

Neuromodulation for enhanced functional integration of neural grafts

Funded in: 2022, 2023, 2024


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Problem: Regeneration of damaged tissue happens slowly if at all
Target: Using stem cells to replace lost neurons and glia
Goal: Wide reaching clinical implications for many types of neural injury

Introduction: A major issue with traumatic damage to the CNS is a loss of cells. Regeneration of damaged tissue happens slowly if at all in the brain and spinal cord, therefore using stem cells to replace lost neurons and glia is an enticing strategy. Recently, the researchers` lab and others have demonstrated impressive engraftment and survivability of stem cells into the spinal cord and new technologies allow them to demonstrate impressive growth of a variety of cell types as well as long term survivability of newly formed neurons and glia from neural stem cell grafts.

Problem/Hypothesis: Despite these advances, better engraftment of complex stem cells has resulted in limited functional improvements. It is the scientists` hypothesis that providing
1) a pre-organized neural graft will allow for a more directed and functionally relevant implant and
2) adding signaling cues from a wireless spinal stimulator will tell our stem cells where to grow and whom to connect with to form a functional circuit.

Methods: The scientists propose to pre-organize neural stem cells of the appropriate type into functional circuits prior to implantation to provide structure and organization. They have used this approach previously with ribbon cell grafts and illustrated that pre-organization provides a benefit to coordinated function of the upper limb. The neuroscientists will then provide a stimulation cue which they have shown influences the growth patterns of typical engrafted neural stem cells.
Expected Results: They believe that together, these two strategies will lead to more functionally organized and directed engraftment and improvement of upper limb function.

Potential Application: Stem cell engraftments and electrical stimulation are both exciting technologies for the treatment of spinal cord injury. In the short term our goal is to target upper limb function, however, should the approach prove effective, there could be wide reaching clinical implications for many types of neural injury.