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  4. Regenerative Medicine for Spinal Cord Injury Using Induced Pluripotent Stem Cells

Regenerative Medicine for Spinal Cord Injury Using Induced Pluripotent Stem Cells

Spine Surg Relat Res, 2024 · DOI: 10.22603/ssrr.2023-0135 · Published: January 1, 2024

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

Spinal cord injury (SCI) is a devastating injury that causes permanent neurological dysfunction. To develop a new treatment strategy for SCI, a clinical trial of transplantation of human-induced pluripotent stem cell-derived neural precursor cells (NPCs) in patients in the subacute phase of SCI was recently initiated. This research focuses on the establishment of cell therapy for chronic SCI, which is more challenging owing to cavity and scar formation. Thus, neurogenic NPC transplantation is more effective in forming functional synapses with the host neurons. Furthermore, combinatory rehabilitation therapy is useful to enhance the efficacy of this strategy, and a valid rehabilitative training program has been established for SCI animal models that received NPC transplantation in the chronic phase.

Study Duration
Not specified
Participants
Patients with spinal cord injury and animal models
Evidence Level
Review Article

Key Findings

  • 1
    Transplanted NPCs secrete neurotrophic factors to attenuate secondary damage and differentiate into neurons that establish synaptic connections with host axons, contributing to functional recovery after SCI.
  • 2
    Selective chemogenetic stimulation of transplanted NPCs enhances synapse formation with host neurons, prevents atrophy of the injured spinal cord, and improves locomotor function.
  • 3
    A combination of NPC transplantation and rehabilitation therapy promotes neuronal differentiation, regeneration, and maturation of neural circuits, enhancing the recovery of motor and sensory functions in chronic SCI.

Research Summary

This review discusses the potential of regenerative medicine, particularly iPSC-derived NPC transplantation, for treating SCI. It highlights the mechanisms underlying functional recovery, including neurotrophic factor secretion, synapse formation, and myelination. The review also covers a clinical trial using iPSC-NPCs in SCI patients and the challenges of treating chronic SCI. It emphasizes the importance of combination therapies, such as rehabilitation, to enhance the efficacy of cell transplantation. Finally, the review addresses strategies to overcome complete paralysis in chronic SCI, including the use of collagen scaffolds secreting hepatocyte growth factor to modify the spinal cord environment and augment cell transplantation therapy.

Practical Implications

Clinical Translation of iPSC-NPCs

The first-in-human clinical trial of iPSC-derived NPC transplantation offers a potential treatment for subacute SCI, pending further evaluation of efficacy.

Enhanced Therapeutic Strategies for Chronic SCI

Combining NPC transplantation with rehabilitation and/or C-ABC infusion can improve cell survival, promote neuronal differentiation, and enhance functional recovery in chronic SCI.

Novel Approaches for Complete SCI

Using HGF-secreting scaffolds in conjunction with cell transplantation shows promise for promoting angiogenesis, reducing inflammation, and improving outcomes in severe chronic SCI with complete transection.

Study Limitations

  • 1
    Efficacy of iPSC-NPC transplantation in acute SCI still requires further evaluation.
  • 2
    Clinical validation for chronic SCI treatment will require additional time.
  • 3
    Overcoming the challenges of treating complete transection injuries remains a significant hurdle.

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