Recapitulation of fibromatosis nodule by multipotential stem cells in immunodeficient mice and identification of putative drug for treating fibromatosis

• Main Authors: Jung-Pan Wang, 王榮磻
• Other Authors: Shih-Chieh Hung
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/93651143490375769618

博士 === 國立陽明大學 === 臨床醫學研究所 === 99 === Musculoskeletal fibromatosis remains a disease of unknown etiology; surgical excision is the standard of care but recurrence rate remains high. Superficial fibromatosis typically presented as subcutaneous nodules due to rapid myofibroblast proliferation followed by slow involution to dense acellular fibrosis. In this study, we demonstrated that fibromatosis stem cells (FSCs) can be isolated from palmar nodule but not from the cord or normal palm tissues. We demonstrated that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105 and CD166 but do not express CD34, CD45, and CD133. We also showed that FSCs are capable of expanding into up to 20 passages and possess multipotentiality into the three germ layer cells, including myofibroblast, osteoblast, adipocyte, chondrocyte, hepatocyte and neural cells. When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human fibromatosis nodule. Two weeks after implantation, the cells expressed immunodiagnostic markers for myofibroblasts α-smooth muscle actin (α-SMA) and type III collagen. Two months after implantation, the number of myofibroblasts diminished and type I collagen became evident. Treatment with trichostatin A (TSA), an anti-fibrogenic compound, inhibited proliferation and differentiation of FSCs in vitro. Treatment with TSA before or after implantation further blocked formation of fibromatosis nodules. These results indicated that FSCs act as cellular origin of fibromatosis and may be used as a promising model to develop new therapeutic interventions.