Promotion of nerve regeneration and motor function recovery in SCI rats using LOCAS‑iPSCs‑NSCs

Stem Cell Research & Therapy, 2024 · DOI: https://doi.org/10.1186/s13287-024-03999-4 · Published: October 14, 2024

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

Spinal cord injury (SCI) is a severe traumatic spinal condition with a poor prognosis. In this study, a scaffold called linearly ordered collagen aggregates (LOCAS) was created and loaded with induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) from human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) to treat SCI in a rat model. The LOCAS scaffold was constructed with good mechanical properties and biomimetic structure. At the same time, the effect of the scaffold in the treatment of the complete transection SCI in rats was investigated by combining with hUCB-MSCs derived iPSCs-derived NSCs, in order to obviously distinguish the differences of SCI repair between LOCS and LOCAS, and provide more possibilities for clinical treatment of SCI. The combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. This development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair.

Study Duration

12 weeks

Participants

40 SPF male SD rats

Evidence Level

Not specified

Key Findings

1
After 12 weeks, rats in the LOCAS-iPSCs-NSCs group exhibited significantly higher BBB scores (8.6) compared to the LOCAS-iPSCs-NSCs group (5.6) and the Model group (4.2).
2
The CatWalk analysis showed improved motion trajectory, regularity index (RI), and swing speed in the LOCAS-iPSCs-NSCs group compared to the other groups.
3
Histological analysis demonstrated enhanced neuronal differentiation of NSCs and nerve fiber regeneration promoted by LOCAS-iPSCs-NSCs, leading to improved motor function recovery in rats.

Research Summary

The combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. LOCAS combined with iPSCs-NSCs showed a good therapeutic effect in the recovery of motor function with higher BBB scores, improved CatWalk trajectories and motor evoked potentials in rats with SCI. Overall, the LOCAS scaffolds presented the uniform pore structure and proper connectivity for cell adhesion and growth, and hindering the invasion of glial scars to guide the linear regeneration of nerves.

Practical Implications

Enhanced Motor Function Recovery

The LOCAS-iPSCs-NSCs group showed superior motor function recovery compared to the LOCS-iPSCs-NSCs and Model groups, indicating a more effective treatment strategy.

Improved Tissue Repair

Histological analysis revealed improved tissue repair in the LOCAS-iPSCs-NSCs group, with reduced cavity structure and more ordered tissue arrangement.

Clinical SCI Repair Possibilities

The development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair, potentially improving patient outcomes.

Study Limitations

1
Underlying molecular mechanisms of the repair in vivo need further elucidation.
2
Biomarkers of inflammatory or oxidative stress are needed to determine for the preliminary judgment on molecular mechanisms.
3
Functional differences between iPSCs-induced NSCs and direct-derived NSCs in this regard is still uncertain.

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