Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms

The Journal of Clinical Investigation, 2012 · DOI: 10.1172/JCI59251 · Published: January 1, 2012

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the potential of human dental pulp stem cells (DPSCs) to promote recovery after spinal cord injury (SCI) in rats. The researchers transplanted DPSCs into rats with completely transected spinal cords and observed significant improvements in hind limb locomotor functions compared to rats receiving bone marrow stromal cells or skin fibroblasts. The DPSCs exhibited three key neuroregenerative activities: inhibiting SCI-induced cell death, promoting axon regeneration by counteracting axon growth inhibitors, and differentiating into mature oligodendrocytes to replace lost cells. The findings suggest that tooth-derived stem cells, like DPSCs, could be a valuable therapeutic resource for SCI treatment due to their cell-autonomous and paracrine neuroregenerative capabilities.

Study Duration

8 Weeks

Participants

Adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Transplantation of human dental pulp stem cells (DPSCs) into completely transected rat spinal cords resulted in marked recovery of hind limb locomotor functions compared to controls.
2
DPSCs inhibited SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, improving the preservation of neuronal filaments and myelin sheaths.
3
DPSCs promoted regeneration of transected axons by directly inhibiting multiple axon growth inhibitors (AGIs) and differentiated into mature oligodendrocytes.

Research Summary

This study demonstrates the neuroregenerative potential of human dental pulp stem cells (DPSCs) in treating spinal cord injury (SCI). DPSCs were transplanted into rats with completely transected spinal cords, leading to significant improvements in locomotor function compared to control groups. The observed recovery was attributed to three major neuroregenerative activities of DPSCs: inhibition of SCI-induced apoptosis, promotion of axon regeneration through AGI inhibition, and differentiation into mature oligodendrocytes. The findings suggest that DPSCs and other tooth-derived stem cells represent a promising therapeutic resource for SCI treatment due to their multifaceted regenerative capabilities and ease of procurement.

Practical Implications

Therapeutic Potential for SCI

Tooth-derived stem cells, particularly DPSCs, may offer a novel cell-based therapy for spinal cord injury due to their neuroregenerative activities.

Targeted Neuroprotection

DPSCs can protect neurons, astrocytes, and oligodendrocytes from apoptosis after SCI, minimizing secondary injury.

Overcoming Axon Growth Inhibition

DPSCs can counteract multiple axon growth inhibitors, promoting axon regeneration in the injured spinal cord.

Study Limitations

1
The study utilized a complete spinal cord transection model in rats, which may not fully represent the complexities of human SCI.
2
Cells were transplanted immediately after injury, an impractical scenario for most human SCI cases.
3
The mechanisms underlying the inhibition of multiple AGIs by SHED-CM and DPSC-CM are currently unknown.

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