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 g ranulation 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 g ranulation tissue had formed around the tubing. This capsule consisted of s everal layers of myofibroblasts and the matrix that they had produced, over laid by a single layer of mesothelial cells. The silastic tubing was remove d and at the same time, the living tube of tissue was everted so that the m esothelium now lined its inner surface. To examine the effect of haemodynam ic factors on myofibroblast differentiation, the 10 mm long tubes of mesoth elial-lined granulation tissue were transplanted into the severed abdominal aorta of the same rat in which the granulation tissue was grown. End-to-en d anastomoses mere performed to extend the existing aorta. At 1, 2, and 3 m onths post-transplantation, the grafts were removed and a progressive incre ase 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 th e active stretching that occurs in vivo could account for differentiation o f the constituent myofibroblasts, tubes of granulation tissue were placed i nto 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 cham ber, where it became surrounded by adrenergic nerves supplying the host iri s. 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 studie s show that myofibroblasts of the granulation tissue encapsulating free-flo ating foreign bodies in the peritoneal cavity further differentiate towards a smooth muscle phenotype when transplanted into a smooth muscle environme nt, namely the abdominal aorta. Similar changes are seen when the granulati on tissue is subjected to active, intermittent stretch is vitro, while the presence of nerves has no effect. Copyright (C) 2000 John Wiley & Sons, Ltd .