Stem Cell Therapies for Central Nervous System Trauma: The 4 Ws—What, When, Where, and Why

Stem Cells Translational Medicine, 2022 · DOI: 10.1093/stcltm/szab006 · Published: February 19, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Traumatic injuries to the brain and spinal cord lack effective treatments to prevent injury progression or replace lost tissue. Stem cell therapy offers potential for reducing initial injuries and replacing lost tissue. Two main strategies exist: transplanting external stem/progenitor cells and encouraging resident stem/progenitor cells to act. This review explores the advantages and disadvantages of these methods for traumatic brain injury (TBI) and spinal cord injury (SCI). Different types of exogenous stem cells may be produced in cell culture and transplanted to select regions, and there are endogenous stem cells that respond to injury and could be used for treatment.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Stem cell transplantation can promote neuroprotection, reduce degeneration, and improve functional outcomes after experimental SCI.
2
Human neural stem cells can reduce inflammation after TBI by increasing the M2/M1 macrophage ratio.
3
Ependymal cells exhibit neural stem cell features from young to mature adults and can be targeted for regeneration regardless of patient age.

Research Summary

CNS trauma remains incurable, but cell therapy shows potential. Exogenous stem cell transplantation or modulation of endogenous stem and progenitor cells can protect tissue, compensate for cell loss, repair neural circuitry, and promote functional recovery in acute-subacute rodent studies. In chronic injuries, tissue replacement by exogenous or endogenous stem cells, likely in multimodal therapies, is necessary. These therapies should enhance graft survival, differentiation, and functional integration. More clinical studies, based on promising experiments and replicated by independent groups, are needed. Academic trials face funding challenges, while commercial actors may prioritize less risky markets.

Practical Implications

Advancing Clinical Translation

More clinical studies should be performed based on the most promising experiments, and replicated by independent groups to validate findings and ensure reproducibility.

Focus on Chronic Injuries

Increased efforts should be directed towards developing cell therapies for chronic TBI and SCI, focusing on strategies that enhance graft survival, appropriate cell fate choices, differentiation, and functional integration.

Standardized Injection Protocols

Standardized injection protocols for cell transplantation should be developed and used to enable better mechanistic conclusions related to the site of implantation in clinical trials.

Study Limitations

1
Tumor formation risks with ESCs and iPSCs.
2
Need for immunosuppression after heterologous transplantation therapy.
3
Ethical concerns regarding the use of fertilized oocytes and embryonic/fetal tissue.

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