Review: Past Presidential Talk Functional Multipotency of Stem Cells and Recovery Neurobiology of Injured Spinal Cords

Cell Transplantation, 2019 · DOI: 10.1177/0963689719850088 · Published: April 19, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This review discusses two main concepts: Functional Multipotency of Stem Cells and Recovery Neurobiology of Injured Spinal Cords. It highlights how stem cells can perform multiple functions beyond just replacing damaged cells, such as reducing inflammation and activating alternative neural pathways. The review emphasizes that conventional neurobiological principles may be a barrier to developing effective treatments for spinal cord injury. It suggests alternative neural and neuromuscular circuitry can restore function post SCI. The concept of 'Functional Multipotency of Stem Cells' suggests stem cells have transiently inducible biofunctions, beyond their ability to differentiate into specific cell types, which helps in mediating cell division, migration, and organ function.

Study Duration

Over the past decade

Participants

Rodents and non-human primates

Evidence Level

Not specified

Key Findings

1
Stem cells, including NSCs and MSCs, can exert multiple biofunctions, such as mitigating secondary injury attacks, promoting neural repair, and activating alternative neural pathways.
2
The impact of NSCs is greater than specific neuronal replacement because they secrete neurotrophic and immunomodulatory factors and form gap junctions.
3
Recovery Neurobiology, the study of how the injured spinal cord uses different neural circuits for function after injury, can be targeted for therapies.

Research Summary

This review summarizes the author's work on functional multipotency of stem cells and recovery neurobiology of injured spinal cords, highlighting the limitations of traditional approaches to SCI treatment. The review emphasizes the importance of stem cells' ability to perform multiple functions, such as reducing inflammation and activating alternative neural pathways, in promoting recovery after SCI. The concept of Recovery Neurobiology is introduced, focusing on how the injured spinal cord can utilize alternative neural circuits for post-injury function, which can be targeted for therapeutic development.

Practical Implications

Therapeutic Targets

Identify and target the essential components of recovery neurobiology, such as PSN, serotonergic modulation, NMJ, and CPG, for neurological, neurosurgical, and functional rehabilitation therapies.

Stem Cell Therapies

Develop stem cell-based multimodal treatments to reconstruct a functional neuromuscular network for communication among limb and trunk muscles, PSN, lumbar or cervical cord CPG, and intra-spinal cord serotonergic modulation.

Comprehensive SCI Treatment Strategies

Design SCI research that concurrently treats abnormality of NMJs and muscles, deficiency of descending and ascending neural facilitation, and CPG malfunction.

Study Limitations

1
Conventional neurobiological principles may be a barrier.
2
Efficacious treatment of neurotrauma remains an unmet clinical demand.
3
Many experiments used neurotrophins, neurotrophic factors, and different signaling pathway manipulation compounds, including those of oncogene activators to increase neuroprotection and axonal growth. In parallel, neutralizing antibodies to Nogo and other myelin, oligodendrocyte or reactive astrocyte-related “inhibitory molecules” were studied widely, albeit yielding contradictory reports.

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