Cell origin in experimental repair of cricoid cartilage defects treated with recombinant human bone morphogenetic protein-2.

We determined the origin of new cartilage and new bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage defects in rabbits randomly divided into eight groups. The cricoid cartilage was split vertically along the anterior midline and a strip was excised from the anterior part of the cricoid cartilage in all rabbits. The perichondrium from the anterior part of the cricoid cartilage was trimmed off in four groups; two groups treated with rhBMP-2 and two control groups. In four other groups, the anterior perichondrium was detached and used as a flap with two groups treated with rhBMP-2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks after surgery. The larynges were removed, fixed and sectioned, and the sections were stained for light microscopy using various cytochemical and immunological techniques. New cartilage was only present close to the host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was present 4 weeks after surgery, although calcified matrix and alkaline phosphatase activity could be detected at the site of cricoid defects as early as 1 week after surgery. The cell proliferation marker Ki-67 was strongly expressed in granulation tissue and bone marrow, and it was moderately expressed in muscles adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors were strongly expressed in cartilage and moderately expressed in adjacent muscles. We conclude that new cartilage originates from the mesenchymal progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone may originate from local muscle.