Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

Cells, 2021 · DOI: https://doi.org/10.3390/cells10081872 · Published: July 23, 2021

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) often leads to severe motor, sensory, or autonomic nervous dysfunction. Effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. Cell therapy has shifted towards extracellular vesicles as an exciting “cell-free” therapeutic modality.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
NSPCs can potentially form relay circuits to bridge functional connectivity between injured spinal cord segments.
2
MSCs exert their therapeutic effects via multiple paracrine mechanisms, including anti-inﬂammation, immunomodulation, neuroprotection, and pro-angiogenesis.
3
EVs demonstrated their efﬁcacy in improving motor recovery across different injury models, mostly by ameliorating the non-permissive microenvironment.

Research Summary

The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. MSCs are appealing because of their “homing” property, i.e., being able to preferentially migrate to the damaged tissues, mediated by inﬂammatory or chemotactic factors and the SDF1-α/CXCR4 axis. EV-based therapy has emerged as an exciting and attractive treatment modality to orchestrate regenerative effects.

Practical Implications

NSPC Transplantation Improvement

Modification of the microenvironment of the injured spinal cord focusing on glial scar formation and inﬂammatory phenotype should be considered to maximize the therapeutic potential of NSPCs in the chronic phase.

Standardized MSC Therapies

Standardized manufacturing processes and potential bioengineering approaches should be introduced to develop more potent and predictable MSC-based therapies.

Clinical Translation of EVs

Key aspects such as safety, scale-up, GMP manufacturing and quality control should be considered in clinical translation of EV-based therapies.

Study Limitations

1
Improve graft survival and host regeneration
2
Establish and maintain functional synaptic connections
3
Guide transplanted cells to appropriate targets and avoid maladaptive connectivity

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