Coadministration of basic fibroblast growth factor-loaded polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence.

Abstract

Basic fibroblastic growth factor (bFGF), a member of the heparin-binding growth factor family, regulates muscle differentiation. We investigated whether coadministration of autologous myoblasts and bFGF-loaded polycaprolactone beads could improve sphincter recovery in a dog model of fecal incontinence (FI). FI was induced by resecting 25% of the posterior anal sphincter in ten mongrel dogs. One month later, the dogs were randomized to receive either PKH-26-labeled autologous myoblasts alone (M group, five dogs) or autologous myoblasts and bFGF-loaded polycaprolactone beads (MBG group, five dogs). The outcomes included anal manometry, compound muscle action potentials (CMAPs) of the pudendal nerve, and histology. The increase in anal contractile pressure over 3 months was significantly greater in the MBG group (from 4.85 to 6.83 mmHg) than that in the M group (from 4.94 to 4.25 mmHg), with a coefficient for the difference in recovery rate of 2.672 (95% confidence interval [CI] 0.962 to 4.373, p = 0.002). The change in the CMAP amplitude was also significantly greater in the MBG group (from 0.59 to 1.56 mV) than that in the M group (from 0.81 to 0.67 mV) (coefficient 1.114, 95% CI 0.43 to 1.80, p = 0.001). Labeled cells were detected in 2/5 (40%) and 5/5 (100%) dogs in the M and MBG groups, respectively. Coadministration of bFGF-loaded PCL beads and autologous myoblasts improved the recovery of sphincter function in a dog model of FI and had better outcomes than cell-based therapy alone.