Background: Dupuytren�s disease (DD) is a slow, progressive fibroproliferative disorder affecting the palms of the\nhands. The disease is characterized by the formation of collagen rich- cords which gradually shorten by the action\nof myofibroblasts resulting in finger contractures. It is a disease that is confined to humans, and a major limiting\nfactor in investigating this disorder has been the lack of a faithful animal model that can recapitulate its distinct\nbiology. The aim of this study was to develop such a model by determining if Dupuytren�s disease (DD)- and control\ncarpal tunnel (CT)-derived fibroblasts could survive in the forepaw of the nude rats and continue to exhibit the distinct\ncharacteristics they display in in vitro cultures.\nMethods: 1x107 fluorescently labeled DD- and CT-derived fibroblasts were transplanted into the left and right\nforepaws of nude rats respectively. Cells were tracked at regular intervals for a period of two months by quantifying\nemitted fluorescent signal using an IVIS imaging system. After a period of 62 days rat forepaw connective tissues were\nharvested for histology and total RNA was isolated. Human-specific probes were used to perform real time\nRT-PCR assays to examine the expression patterns of gene products associated with fibrosis in DD. Rat forepaw skin\nwas also harvested to serve as an internal control.\nResults: Both CT- and DD-derived fibroblasts survived for a period of 62 days, but DD-derived cells showed a significantly\ngreater level of persistent fluorescent signal at the end of this time than did CT-derived cells. mRNA expression levels of\n?-smooth muscle actin (?-SMA), type I- and type III- collagens were all significantly elevated in the forepaw receiving DD\ncord-derived fibroblasts in comparison to CT-derived fibroblasts. Masson�s trichrome stain confirmed increased collagen\ndeposition in the forepaw that was injected with DD cord-derived fibroblasts.\nConclusions: For the first time we describe an animal model for Dupuytren�s disease at the orthotopic anatomical\nlocation. We further show that gene expression differences between control (CT) and diseased (DD) derived fibroblasts\npersist when these cells are transplanted to the forepaw of the nude rat. These preliminary findings indicate that, with\nfurther refinements, this animal model holds promise as a baseline for investigating novel therapeutic regimens to\ndetermine an effective strategy in treating DD.
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