The purpose of this experimental paper is to evaluate in vitro characteristics of cells from Dupuytren’s nodules and cords in an effort to determine their respective roles in the evolution of palmar contractures. The authors outline the two competing schools of thought regarding the formation of contractile cords. First, that the nodule, or proliferative phase, develops directly and linearly into the cord in a phenotypic transformation. Second, that the nodule and the cord represent different structures entirely and are present at different phases of the disease as separate but related entities. Their study attempts to resolve this issue by using two parallel in vitro cell culture lines derived from Dupuytren’s nodules and cords in four patients. Two characteristics were measured in populations of cells from Dupuytren’s nodules and cords at early and late passages of cell lines, representing early and late stages of fibroblast maturation. These were contraction of fibroblast-populated collagen lattices and changes in gap junctional intercellular communication. The first marker is directed at quantifying the contractile properties of cells from both nodules and cords at varying stages of cell life. The second marker is directed at determining the relative maturity of the cell lines in an effort to correlate this with the phases of the disease. According to the authors, immature cells would be expected to have less intercellular communication between gap junctions than mature cell types. Early passage nodule fibroblasts contracted by 64%, versus 40% for late passage nodule cells (p<0.01). The values for early and late cord fibroblasts were 46 and 37%, respectively. The coupling index of the cell lines was measured as a relative indicator of the number of cell-sharing gap junction channels between cells. Early passage nodules exhibited a lower coupling index of 2.5 + 0.4, versus 4.0 + 0.4 for early cord cells (p<0.01). The values for late passage nodule and cord cells were equivalent, with no statistically significant difference. Thus, the coupling index of cord cells showed no change with passage through cell culture, while nodules changed significantly over time, approaching the value of cord cells by passage 8. This latter value also corresponded to the value for normal dermal fibroblasts.
The results of this study appear to support the hypothesis that Dupuytren’s nodules and cords are a progression of one precursor cell type from one phenotypic expression (nodule) to another (cord). This in vitro model allows a cellular representation of the maturation of Dupuytren’s cells over time, as harvesting these cells sequentially in vivo from patients with Dupuytren’s disease is not practical. The finding that early nodule cells have characteristics which would implicate them as the “active” cells in Dupuytren’s disease, with a higher contractile rate and a lower coupling index, is somewhat surprising, as clinical contractures do not appear until after the formation of cords. The authors use the evidence collected in this study to postulate that the proliferative stage of Dupuytren’s disease is limited to the formation of nodules. The maturation into the cord phenotype that attaches the contractile unit, the nodule, to the dermal elements, is what produces contractures over time. Their study does indeed appear to support the notion of a linear cellular maturation from more active nodule to less active cord. But the leap to determining the actual pathophysiologic mechanism of contracture formation remains somewhat elusive. Hopefully, further work on the cellular characteristics of Dupuytren’s tissue, with inclusion of study on growth and genetic factors, will lead to a true understanding of the pathogenesis (and control) of this disease.
Plastic and Reconstr Surg