Matrix-mediated cellular rejuvenation

Abstract

Biomaterial surface morphology and chemistry influence cell responses mediated via signaling cascades that regulate a wide range of metabolic processes. These responses may range from changes in surface adhesion and remodeling of the extracellular matrix to activation of cytokine, cytoskeletal and other biochemical pathways regulating or modulating cellular morphology and function. The present study has focused on collagen Type I, a key extracellular matrix protein, and its potential impact on the process of cellular aging. This study was undertaken for several reasons. First, several investigators reported that growth of cells on a collagen matrix markedly enhanced the resistance of cells to stresses. Second, a large body of accumulated data strongly indicated a relationship between the potential to respond to stresses and cellular aging with the former strongly influencing the rate of the latter. Finally, it has been recently demonstrated that in aged cells one of the key aging-related processes previously considered irreversible, attenuation of the expression of a major stress response protein, Hsp70, can be reversed. This fact together with a probable regulatory role of the stress response potential in cellular aging suggested a possibility that the cellular aging process as a whole can be altered. Indeed, in the present study, growth on a denatured collagen matrices reversed in aged cells not only the attenuation of Hsp70 expression but also other aging-related processes, such as beta-galactosidase expression, increase in protein oxidation and changes in cell morphology. Moreover, it appeared to reduce the rate of aging in young cells. Understanding the nature of collagen matrix-mediated cellular rejuvenation might suggest approaches for interfering with organismic aging. Some immediate applications include cell rejuvenation for purposes of cloning and reduction of the rate of aging during expansion of stem cells for purposes of tissue engineering.