title: Recapitulation of fibromatosis nodule by multipotential stem cells in immunodeficient mice.
abstract: Musculoskeletal fibromatosis remains a disease of unknown etiology. Surgical excision is the standard of care, but the recurrence rate remains high. Superficial fibromatosis typically presents as subcutaneous nodules caused by rapid myofibroblast proliferation followed by slow involution to dense acellular fibrosis. In this study, we demonstrate that fibromatosis stem cells (FSCs) can be isolated from palmar nodules but not from cord or normal palm tissues. We found that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105, and CD166 but do not express CD34, CD45, or CD133. We also found that FSCs are capable of expanding up to 20 passages, that these cells include myofibroblasts, osteoblasts, adipocytes, chondrocytes, hepatocytes, and neural cells, and that these cells possess multipotentiality to develop into the three germ layer cells. When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human fibromatosis nodules. Two weeks after implantation, the cells expressed immunodiagnostic markers for myofibroblasts such as α-smooth muscle actin and type III collagen. Two months after implantation, there were fewer myofibroblasts and type I collagen became evident. Treatment with the antifibrogenic compound Trichostatin A (TSA) inhibited the proliferation and differentiation of FSCs in vitro. Treatment with TSA before or after implantation blocked formation of fibromatosis nodules. These results suggest that FSCs are the cellular origin of fibromatosis and that these cells may provide a promising model for developing new therapeutic interventions.
authors: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Jung-Pan
authors: JP
authors: Wang
authors: Yun-Ju
authors: YJ
authors: Hui
authors: Shih-Tien
authors: ST
authors: Wang
authors: Hsiang-Hsuan Michael
authors: HH
authors: Yu
authors: Yi-Chao
authors: YC
authors: Huang
authors: En-Rung
authors: ER
authors: Chiang
authors: Chien-Lin
authors: CL
authors: Liu
authors: Tain-Hsiung
authors: TH
authors: Chen
authors: Shih-Chieh
authors: SC
authors: Hung
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D005350:Fibroma / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; D024061:Collagen Type III; D006877:Hydroxamic Acids; C544013:alpha-smooth muscle actin, mouse; C012589:trichostatin A