Haemopoietic origin of myofibroblasts formed in the peritoneal cavity in response to a foreign body

This study utilized both in vivo and in vitro techniques to investigate whe ther cells of bone marrow origin can differentiate into smooth muscle-like cells (myofibroblasts) with contractile filaments and proteins. Female C57B L/6 mice expressing the Ly5.2 antigen on the surface of their haemopoietic cells had four pieces of silastic tubing (3 x 0.5 mm outer diameter) or boi led blood clot (2-3 mm diameter) placed in their peritoneal cavity. After 3 , 5, 7 and 14 days (n = 4/group) the implants were removed and those that h ad remained free-floating were processed for light microscopy, immunohistoc hemistry and electron microscopy. in the first 3-5 days, rounded cells adhe red to the entire surface of the tubing then flattened. These cells stained with fluoresceinated antibodies to Ly5.2 showing that they were derived fr om haemopoietic cells. By 14 days the cells had become elongated and multil ayered in a collagen matrix, forming a thick tissue capsule around the tubi ng or boiled clot. They contained contractile filaments and stained with an tibodies to alpha-smooth muscle actin but no longer stained for Ly5.2. A se parate set of female C57BL/6 Ly5.2 mice were X-irradiated to destroy bone m arrow then immediately transfused with 10(6) nucleated bone marrow cells ta ken from the femur and tibia of a congenic strain of male mice expressing t he Ly5.1 allele. Eight of the female mice with successful engraftment (80-9 9%) had silastic tubing implanted in the peritoneal cavity. After 14 days, in situ hybridization with Y chromosome probe confirmed the male donor, and thus bone marrow, origin of the elongated cells that formed the capsule. I n vitro studies showed that cells of the murine macrophage cell lines RAW 2 64.7 and J774 express alpha-smooth muscle actin after exposure to the cytok ine gamma-interferon in vitro. These data show that bone marrow-derived cel ls can differentiate into smooth muscle-like cells and raises the possibili ty that blood-derived cells may contribute to the development of fibro-prol iferative vascular diseases such as atherosclerosis. Copyright (C) 2000 S. Karger AG, Basel.