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  4. Caudalized human iPSC-derived neural progenitor cells produce neurons and glia but fail to restore function in an early chronic spinal cord injury model

Caudalized human iPSC-derived neural progenitor cells produce neurons and glia but fail to restore function in an early chronic spinal cord injury model

Exp Neurol, 2013 · DOI: 10.1016/j.expneurol.2013.07.010 · Published: October 1, 2013

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

The study investigates the potential of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSCs) to repair chronic spinal cord injury (SCI). hiPSCs were differentiated into region-specific (caudal) NPCs and transplanted into a clinically relevant model of early chronic cervical SCI. The transplanted cells successfully integrated into the injury environment and produced multiple neural lineages. However, the integration and differentiation of hiPSC-derived neural cells did not lead to significant improvement in forelimb function or induce allodynia. These findings suggest that while hiPSCs hold promise for SCI treatment, future research should focus on identifying specific hiPSC-derivatives or co-therapies to restore function in the early chronic injury setting.

Study Duration
8 Weeks
Participants
Adult female Long-Evans rats
Evidence Level
Not specified

Key Findings

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    Caudalized hiPSC-NPCs can be successfully transplanted into an early chronic cervical SCI model and survive for up to two months post-transplant without risk of overgrowth or loss of function.
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    The transplanted hiPSC-NPCs differentiated into neurons, astrocytes, and oligodendrocytes in vivo, demonstrating multipotentiality.
  • 3
    Despite integration and differentiation, transplantation of hiPSC-NPCs did not result in significant improvement in forelimb function or reduction in allodynia compared to control groups.

Research Summary

This study examined the pre-clinical potential of NPCs derived from human induced pluripotent stem cells (hiPSCs) to repair chronic SCI. hiPSCs were differentiated into region-specific (i.e. caudal) NPCs, then transplanted into a new, clinically relevant model of early chronic cervical SCI. The study established conditions for successful transplantation of caudalized hiPSC-NPCs and demonstrated their ability to integrate and produce multiple neural lineages in the early chronic injury environment. Survival and integration of hiPSC-derived neural cells in the early chronic cervical model did not lead to significant improvement in forelimb function or induce allodynia.

Practical Implications

Future Research

Future research should focus on the specific hiPSC-derivatives or co-therapies that will restore function in the early chronic injury setting.

Clinical Relevance

The cervical injury model developed corresponds closely to the most common forms of spinal cord injury.

Cellular Plasticity

hiPSC-derived neural progenitor cells show promise as a potential method to introduce cellular plasticity in the early chronically injured spinal cord.

Study Limitations

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