Regeneration in the Rat Sciatic Nerve Using Collagen Tubes and VEGF

Nerve regeneration was studied in the rat model using a collagen tube filled with bone marrow mesenchymal stem cells (MSC). Some MSCs were transfected with a plasmid containing the gene for VEGF, a growth factor which reportedly affects the outgrowth of blood vessels, Schwann cells, and axons.

In 25 rats, a 10-mm gap was created in the left sciatic midthigh. A collagen nerve guide was sutured into place to enclose the gap. Four experimental groups received (20 μl) saline, Matrigel, Matrigel + MSC, or Matrigel + MSC/VEGF. After 21 days, the repair site was exposed and fixed in situ. Tissues were embedded for transverse 1-μm sections and toluidine blue staining. A region 3 mm from the proximal stump was selected to determine by point counting the volume fractions of blood vessels, axons, endoneurial cells, and endoneurial space.

Results showed that the volume fraction of axons (myelinated + non-myelinated) was significantly greater in the saline group compared to the three other groups with Matrigel. The decrease in vessels in the Matrigel group and recovery by the addition of MSC and VEGF were not significantly different from saline. The increase in cells in the three groups with Matrigel was not significant. The extracellular space was large in all four groups at 21 days postoperatively.

Collagen tubes are suitable, temporary guides, as suggested by the longitudinal orientation of axonal and vascular growth, as well as cuff breakdown with cellular infiltration. Axonal regeneration was greatest in the absence of Matrigel, which may be an undesirable carrier.