Early fibrodysplasia ossificans progressiva-like lesion formation in nude mice following implantation of lymphoblastoid cells from FOP patients

Fibrodysplasia ossificans progessiva (FOP) is a genetic disease of progressive, heterotopic ossification, resulting in profound decreased mobility. To investigate the pathophysiology of this condition, lymphoblastoid cells (LCLs) derived from patients with FOP or unaffected family members were implanted subcutaneously into athymic (nude) mice. Cells from unaffected individuals persisted as small masses with little evidence of a fibrotic or angiogenic response. In contrast, cells from patients with FOP gave rise to palpable, solid, fibrotic cellular masses in the animals. Histological and immunohistochemical evaluation revealed that FOP cells proliferated in the host and induced a fibrotic and angiogeneic response similar to the early-stage FOP lesions in patients, but did not progress to form ettopic cartilage or bone. These results de monstrate that lymphoblastoid cells from patients with FOP induce early preosseous FOP-like lesions in mice, but are not sufficient to induce heterotopic ossification in immunocompromised host animals. Implantation of FOP-derived cells in nude mice provides a useful model system for examining the earliest stages of the disease.