The effect of environmental cues on the differentiation of myofibroblasts in peritoneal granulation tissue

This study investigated the effect of haemodynamic stress, active stretch, and neuronal input on the differentiation of myofibroblasts in peritoneal granulation tissue. Lengths of silastic tubing (10 mm long x 3 mm diameter) were placed in the peritoneal cavity of the rat. By 2 weeks, a capsule of granulation tissue had formed around the tubing. This capsule consisted of several layers of myofibroblasts and the matrix that they had produced, overlaid by a single layer of mesothelial cells. The silastic tubing was removed and at the same time, the living tube of tissue was everted so that the mesothelium now lined its inner surface. To examine the effect of haemodynamic factors on myofibroblast differentiation, the 10 mm long tubes of mesothelial-lined granulation tissue were transplanted into the severed abdominal aorta of the same rat in which the granulation tissue was grown. End-to-end anastomoses were performed to extend the existing aorta. At 1, 2, and 3 months post-transplantation, the grafts were removed and a progressive increase in the percent volume fraction of myofilaments (% V(v)myo) was observed (from 35.7+/-1.6% to 58.7 3+/-1.4%; p<0.05). To determine whether the active stretching that occurs in vivo could account for differentiation of the constituent myofibroblasts, tubes of granulation tissue were placed into a mechanical device in which they underwent continuous stretching of 5-10% elongation from the resting position at 50 cycles per minute for 3, 24 or 72 h. This caused a significant (p<0. 05) increase in %V(v)myo after 72 h. Granulation tissue was also transplanted into the rat anterior eye chamber, where it became surrounded by adrenergic nerves supplying the host iris. Two months after implantation, there was no significant change in the %V(v)myo of the myofibroblasts (35.7+/-1.6% to 33.3+/-2.7%). These studies show that myofibroblasts of the granulation tissue encapsulating free-floating foreign bodies in the peritoneal cavity further differentiate towards a smooth muscle phenotype when transplanted into a smooth muscle environment, namely the abdominal aorta. Similar changes are seen when the granulation tissue is subjected to active, intermittent stretch in vitro, while the presence of nerves has no effect.