Human stem cell–derived neurons and neural circuitry therapeutics: Next frontier in spinal cord injury repair

Experimental Biology and Medicine, 2022 · DOI: 10.1177/15353702221114099 · Published: December 1, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) is a devastating condition, and researchers are exploring stem cell-based therapies to repair the damage. A new approach involves using human-induced pluripotent stem cells (hiPSCs) to generate spinal motor neurons that can be transplanted into the injured spinal cord. These neurons are derived from neuromesodermal progenitors (NMPs), which are early precursors of spinal cord tissue. Transplanting these pre-formed neuronal circuits aims to restore function by integrating with the host's neural circuitry. This review discusses the challenges and advancements in stem cell-based SCI therapies, highlighting the potential of NMP-derived neurons and preformed neuronal circuitry to improve functional recovery for SCI patients.

Study Duration

Not specified

Participants

Animal models (rats) and human stem cells

Evidence Level

Review

Key Findings

1
The review highlights the potential of using human-induced pluripotent stem cells (hiPSCs) to generate spinal motor neurons from neuromesodermal progenitors (NMPs) for SCI therapy.
2
Transplantation of preformed neuronal circuitry, incorporating NMP-derived spinal motor neurons, interneurons, and OPCs, has demonstrated functional integration in a rat hemicontusion model of SCI.
3
The review underscores the importance of anatomical region-specific spinal motor neurons and support cells as preformed neuronal circuitry for effective SCI treatment in animal models.

Research Summary

The ability to generate stem cell–derived neurons for spinal cord injury (SCI) therapeutics, which survive and functionally integrate when transplanted, brings neuronal circuitry restoration strategies to the forefront. Challenges persist with the current use of multipotent progenitor cells for complete and sufficient differentiation to neurons, exacerbated by a cytokine complex SCI microenvironment. The next generation of SCI cell therapies will apply the right spinal motor neuron subtype and advanced delivery in innovative platforms, including preformed transplantable neuronal circuitry, that can be combined with electrostimulation to accelerate functional recovery outcomes for SCI patients.

Practical Implications

Therapeutic Development

NMP-based neurotechnologies offer new avenues for developing targeted cell therapies for SCI, potentially leading to more effective treatments.

Clinical Translation

The use of preformed neuronal circuitry and advanced delivery platforms can improve the reproducibility and efficacy of stem cell transplantation in SCI patients.

Combination Therapies

Integrating stem cell therapies with biomimetic scaffolds and electrostimulation may enhance functional recovery outcomes for SCI patients.

Study Limitations

1
Challenges in achieving complete and sufficient differentiation of multipotent progenitor cells into neurons.
2
The complex cytokine microenvironment of the SCI site poses a significant obstacle for therapeutic cell survival and integration.
3
Limited clinical trial data available for hiPSC-derived neural progenitor cells in SCI treatment.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury