Combination of Engineered Schwann Cell Grafts to Secrete Neurotrophin and Chondroitinase Promotes Axonal Regeneration and Locomotion after Spinal Cord Injury

The Journal of Neuroscience, 2014 · DOI: 10.1523/JNEUROSCI.2661-13.2014 · Published: January 29, 2014

Simple Explanation

This study explores a new method for treating spinal cord injuries by transplanting special cells into the damaged area. These cells, called Schwann cells, are modified to release substances that help nerve fibers regrow and overcome obstacles in the injury site. The researchers used a combination of Schwann cells that release a growth-promoting substance (neurotrophin) and an enzyme (chondroitinase) that breaks down scar tissue. They found that this combination improved nerve fiber regeneration and the ability of rats with spinal cord injuries to move and sense touch. The results suggest that using modified Schwann cells to deliver these substances could be a promising way to treat spinal cord injuries in humans.

Study Duration

13 Weeks

Participants

280 Adult Female Fischer Rats

Evidence Level

Level II: Experimental study

Key Findings

1
Transplantation of SCs secreting both D15A and ChABC yielded the best responses including the largest number of SC myelinated axons and more propriospinal axons.
2
The combination of D15A and ChABC transplants led to more brainstem neurons projecting caudal to the transplant, increased 5-HT-positive axons and significant improvement in aspects of locomotion.
3
The combination of D15A and ChABC transplants led to an improvement in mechanical and thermal allodynia.

Research Summary

The study investigates the effects of transplanting Schwann cells (SCs) genetically modified to secrete a bifunctional neurotrophin (D15A) and chondroitinase ABC (ChABC) into a subacute contusion injury in rats. The results showed that SCs secreting both D15A and ChABC yielded the best responses, including increased numbers of SC myelinated axons, more propriospinal axons, and improved locomotor and sensory function. This is the first evidence that the combination of SC transplants engineered to secrete neurotrophin and chondroitinase further improves axonal regeneration and locomotor and sensory function.

Practical Implications

Therapeutic Potential

The combination of genetically modified SCs secreting neurotrophin and ChABC has significant therapeutic potential for treating SCI.

Clinical Application

The findings point to the clinical application of genetically modified, autologous SC transplantation for spinal-cord-injured persons.

Combination Therapy

Neurotrophin gradients and modification of the graft/spinal cord interfaces will be among the essential components of a successful SC combination therapy.

Study Limitations

1
ChABC treatment will not reduce other inhibitory ligands such as semaphorins, ephrins, NoGo, OMpg, and MAG.
2
The higher concentration of neurotrophin in the implant than in the surrounding host tissue may prevent axons from leaving the transplant.
3
Analysis to compare neuroprotection of the spared white matter among the experimental groups was found not to be feasible because the graft/white matter interfaces were not distinct enough in the ChABC-treated animals.

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