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  4. Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing

Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing

STEM CELLS TRANSLATIONAL MEDICINE, 2018 · DOI: 10.1002/sctm.17-0269 · Published: August 7, 2018

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

Spinal cord injuries (SCI) have devastating consequences and lack effective regenerative treatments. The authors developed a method to generate myelinating oligodendrogenic tripotent neural progenitor cells (oNPCs) directly derived from a patient’s own somatic bone marrow cells. Results of this study show a promising approach using oNPCs to replace cells, re-myelinate axons and provide trophic support for tissue sparing, ultimately resulting in functional recovery post-SCI. The study generates a novel tripotent human NPC, which has been biased prior to transplant toward an oligodendrogenic fate, and assesses its efficacy in a highly clinically relevant contusion-compression model of T-cell deficient rodent thoracic SCI.

Study Duration
5 Months
Participants
RNU rats and NOD/SCID mice
Evidence Level
Not specified

Key Findings

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    Transplanted cells showed significant migration along the rostro-caudal axis and proportionally greater differentiation into oligodendrocytes.
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    These cells promoted perilesional tissue sparing and axonal remyelination, which resulted in recovery of motor function.
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    There was no evidence of tumor formation even after 5 months of observation.

Research Summary

The purpose of this study was to first generate oligodendrogenic-NPCs (oNPCs) efficiently from established human NPC lines, including drNPCs and iPSCs, using our novel method. We next assessed the efficacy and safety of the drNPC-derived oNPCs grafted in a rodent model of SCI. The present study is particularly important as it is the first study to our knowledge which describes human drNPCs biased toward an oligodendrogenic fate for neural repair and regeneration following SCI.

Practical Implications

Therapeutic Potential

Human drNPC-derived oNPCs are an exciting therapeutic option to regenerate the traumatically injured spinal cord with clear evidence of efficacy and data suggestive of safety in vivo.

Clinical Translation

This process represents a feasible approach to induce and transplant autologous directly reprogrammed cells originating from the patient’s own somatic cells in a real-istic time frame and decreasing the chance of rejection and increasing the survival of transplants.

Remyelination and Neuroprotection

Cells derived from transplanted oNPCs are capable of remyelinating host axons and generating new neurons. Furthermore, engrafted oNPCs migrated throughout the lesional and perilesional regions, reduced the total lesional area, and increased white matter volumes due to differentiation of myelinating oligodendrocytes and preservation of host tissues.

Study Limitations

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