Comparitive Study of Matrix Metalloproteinase (I and II) Function on Different Fibroblast Culture Models


Khoramizadeh M.R.* *, Pezeshki M. , Safavifar F. , Ghahari A. ,

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Introduction: The process of wound healing sets in motion a complex and dynamic series of events, which includes the remodeling of the extracellular matrix degradation of matrix proteins, predominantly collagen fibers, mediated by matrix metalloproteinase (MMPs). Our aim was to demonstrate whether fibroblasts derived from various strains of human fetal foreskin (FS) and adult skin (AS), when cultivated in a 3-D tissue model, exhibit different matrix metalloproteinase activities as compared to plastic environment. Material and Methods: A total of 13 cell strains, 8 and 5 strains of fetal foreskin and adult dermal fibroblasts, respectively, were grown under sterile conditions. Synchronized cultures up to 80-90% confluency of either study groups were used for further analyses. The rates of collagenase activity and gelatinase zymography of conditioned medium derived from adult cells relative to fetal fibroblasts in plastic vs. 3-D gel were determined and compared. Results: Adult fibroblasts showed higher collagenase I activity vs. FS strains both in plastic and in 3-D substrate (14.38±1.33. vs. 9.79±2.27 in plastic, and, 27.05±1.28 vs. 25.2±2.97.± in 3-D gel, (p<0.05). FS strains produced nearly three times more collagenase I in 3-Dgel than in plastic; this increased activity rate was less than two times for AS strains. This finding was further added by enhanced gelatinase activities seen in both strains in 3-D gel. However, FS strains expressed more gelatinolytic activities in 3-Dgel, indicating different cellular functions derived from varied morphologies. Conclusions: These findings showed physiological differences in matrix components and could be due to phenotypic variations adopted by cells in response to local milieu, e.g. aging process. However, more studies are needed to address the question whether these phenotypic discrepancies could be further modified by the action of either growth modulators or cytokines