The induction of smooth muscle cell proliferation in vitro using an organ culture system

Agents which promote vascular smooth muscle cell (SMC) proliferation are still unknown and cannot be readily defined in vivo. To examine this problem, we have developed a technique to maintain arteries in culture for more than two weeks without loss of endothelium and without loss of contractility. These vessel segments were maintained in 30% calf serum, and yet SMC replication rate in the media was found to be below 0.1% per day. No loss of medial cells nor medial necrosis was observed. Gentle endothelial denudation did not cause intimal thickening. If, in addition to denudation, direct mechanical injury was applied, then the replication rate of intimal SMC was found to be 60% per day during the first week. These cells were confirmed to be of SMC origin using cell specific antibodies. Since SMC start to proliferate after mechanical injury and not after application of serum, we conclude in our experimental model that exogenous growth factors play a minor role in the process of induction of proliferation of these cells.