ESHU for Optimizing BMSC Transplant Survival and their Spinal Cord Repair Efficacy
Funded in: 2013, 2014, 2015, 2016
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Problem: Secondary damage is responsible for a progressive increase of the tissue damage and functional deficits. Bone marrow stromal cell transplantation may be beneficial but not yet optimal because of the poor cell survival.
Target: A new hydrogel that improves the survial of the transplanted cells
Goal: Obtain a mixed hydrogel/cells compound that once injected will limit secondary damage.
Spinal cord injury (SCI) causes so far incurable motor and sensory deficits.
The acute tissue damage affects the neural cells and their axons but also extends to all other tissue structures like the blood vessels and sets on a cascade of tissue reactions (neuroinflammation), causing additional cell death and myelin loss. This secondary damage is responsible for a progressive increase of the tissue damage, the lesion size and the functional deficits. While the acute cell death cannot be prevented, strategies aimed at preventing secondary degeneration represent a potentially effective therapy for SCI.
In animal models of SCI it was demonstrated that the transplantation of bone marrow stromal cell (BMSC) in the lesioned spinal cord could be a promising approach to limit the secondary tissue damage resulting in improved motor function. So far the neuroprotective effects of the BMSC transplant were limited by the low survival in damaged nervous tissue, the BMSCs die early after injection into the damaged spinal cord.
Dr. Oudegas team found that the substance poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) promotes BMSC transplant survival correlating with tissue sparing. ESHU dissolves in water and undergoes spontaneous phase transition with increasing temperatures to form a physical gel at 37°C, the human body temperature. Injected into the damaged spinal cord, the gel conforms to the shape of the lesion. ESHU has a functional group, which allows adding functional molecules. How ESHU supports BMSC transplant survival is unknown, but it is hypothesized that antioxidative effects of ESHU prolong the presence of transplanted BMSCs in the contused spinal cord.
This project will:
- investigate whether ESHU exerts antioxidative effects that prolong the presence of transplanted BMSCs in the contused spinal cord.
- determine whether ESHU functionalized with further reactive molecules enhances BMSC transplant survival and increases tissue sparing and motor function recovery after spinal cord contusion.
The results will provide fundamental principles that challenge current BMSC-based repair strategies, which will meaningfully impact people with SCI.