The Assessment of Efficiency of Local Delivery Pathways of Therapeutic Genes in Murine Spinal Cord Injury: Correlation of Structure and Function Parameters

The aim of the investigation was to assess the efficiency of posttraumatic regeneration of murine spinal cord in immediate single administration of human umbilical cord mononuclear blood cells transfected by pBud-VEGF-FGF2 plasmid, and direct injection of this plasmid in the damage area. Two problems were to be solved: to reveal the correlation between morphological and functional spinal cord indices and estimate the amount of S100B⁺-cells in the conditions of local delivery of vegf and fgf2 genes on cellular carriers or in direct gene therapy.

Materials and Methods. The rats after dosing contusion spinal cord injury (ТV_III level) were divided into four groups. One group animals were administered umbilical cord mononuclear blood cells transfected by pBud-VEGF-FGF2 plasmid in damage area, the animals of another group were administered the same cells transfected by pEGFP-N2 plasmid in similar conditions. The animals of other two groups were injected pBud-VEGF-FGF2 plasmid in the same area in one case, and another — the same amount of pEGFP-N2 plasmid.

Results. We established direct negative correlation between the damage area size and the motor function recovery index in experiments with a direct injection of pBud-VEGF-FGF2 plasmid. The highest correlation coefficient was obtained at the distance of 5 mm away from injury epicenter. In case of transplantation of cells transfected by this plasmid there was no correlation. The number of S100B⁺-cells in exterior zones of white matter at the distance of 1.5 cm from the injury epicenter under the conditions of direct gene delivery increased by 46% (p<0.05). If umbilical cord blood cells transfected by pBud-VEGF-FGF2 plasmid were administered the index grew by 55% (p<0.05).

Conclusion. In the course of regeneration after contusion spinal cord injury, the damage area reduction and related motor function recovery is more effective in direct gene therapy compared to the delivery of the same genes on cellular carriers.

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Shaymardanova G.F., Mukhamedshina Y.О., Chelyshev Y.А. The Assessment of Efficiency of Local Delivery Pathways of Therapeutic Genes in Murine Spinal Cord Injury: Correlation of Structure and Function Parameters. Sovremennye tehnologii v medicine 2013; 5(3): 16