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Great numbers of studies have been done on myofibroblasts in recent years. Advancement in diagnostic techniques has permitted accurate identification of this enigmatic cell. Controversies still continue regarding its origin. Broad spectrum of activities of myofibroblasts in diverse group of conditions ranging from wound healing to benign proliferations to malignancies has drawn the attention of multiple disciplines towards this cell. It is clear that our understanding of the myofibroblast, its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally. Recently, some unpublished studies have shown that cardiac myofibroblasts retain differentiated phenotype for longer period than lung and subcutaneous myofibroblasts. Considering the heterogeneity of their precursors, question arises that, are all myofibroblasts equally responsive to mechanical factors? Does it matter which mechanical condition cells have experienced to become differentiated? Many more such questions are still left unanswered.