Comparative Evaluation of Agents On Dupuytren's Contracture and Keloid Fibrosis

Purpose: Neoplasms are the result of abnormal cell proliferation. Dupuytren’s contracture and keloid scar are characterized by fibroblast hyperproliferation and collagen deposition resulting in abnormal scar tissue. This similarity has lead to investigation of antiproliferative/antimetabolite agents used in the treatment of neoplasms to control/alleviate Dupuytren’s contracture and keloid scar. While individual drug treatments show some decrease in contraction, there has not been a reported investigation comparing antiproliferative/antimetabolite substances and their proposed mechanism of action. The purpose of this experimental series is to comparatively evaluate respective levels of TGFβ1 and 2, and the rate and extent of contraction of fibroblasts derived from keloid scar and Dupuytren’s contracture compared with control and when treated with antiproliferative/antimetabolite agents.

Methods: Fibroblasts obtained from explants of Dupuytren’s contracture and palmar fascia (control) as well as keloid scar and normal scar were utilized. These fibroblast populated collagen lattices (FPCL) were exposed to 72 hours of non-cytotoxic doses of 5-Fluorouracil, Methotrexate, Paclitaxel, Tamoxifen, Mitomycin-C, and Bleomycin. Standardized photography was utilized to evaluate FPCL contraction. The supernatant of FPCL was analyzed using TGFβ1 and 2 immunoassays.
Results: Abnormal scar types showed increased contraction and when compared with controls. Dupuytren’s and keloid fibroblasts' FPCLs showed sensitivity after exposure to particular antiproliferative agents causing a significant decrease of contraction (p<0.05). While there was no statistically significant difference between drugs with Dupuyten's contracture fibroblasts, there was a significant difference found with contraction of keloid derived FPCLs noting differences in inhibition of contraction when treated with particular agents (p<0.005). Expression of TGF-β2 of untreated FPCLs was significantly increased (p<0.05) in abnormal scar tissue compared with control scar. Treatment of fibroblasts with all drugs tested resulted in significant down-regulation of TGF-β2 expression compared to untreated fibroblasts from these abnormal scar types. TGF-β1 secretion did not result in a significant difference between abnormal scars when compared with controls. Various antiproliferative treatment agents on abnormal scar groups decreased the expression of TGF-β1 compared to the untreated controls.
Conclusion: Non-cytotoxic doses of antiproliferative/antimetabolite agents used in this study decrease FPCL contraction significantly when compared with untreated FPCL. These agents also cause a significant decrease in both TGFβ1 and 2, a likely cause decreased contraction. Improved function, range of motion, and cosmesis are positive clinical effects of less scarring.