Many amphibians can regrow entire limbs and organs, however, mammalian regeneration is essentially unheard of in the natural world. Recently, we have identified a remarkable mammal that has regenerative ability - the African Spiny Mouse (Acomys). Preliminary data from collaborations across our University are exciting and intriguing: Acomys tissues do not exhibit fibrosis (scarring) when repairing damage. After inducing injury to the skin, ear, heart, brain, and spinal cord, we find minimal, if any, fibrosis markers stereotypical of mammalian pathologies. Understanding fibrosis is the key to unlocking the secrets of regeneration. This research will test the hypothesis that mechanical stimuli can direct regeneration by providing controlled mechanical stimulation of cells from regenerative (Acomys) and normal (Mus) mice. If successful, we will have identified mechanisms to control scarring in adult mammals for the first time.
The long-term goal of the research is to identify the dominant mechanism of scar-free wound healing. We hypothesize that regenerative cells may not only be programmed to respond to injury differently but may also receive different physical signals. The key research objectives of this project are to (1) Establish the importance of mechanical tension cues on integrin expression and downstream signaling in cells from regenerative and fibrotic models, and (2) Define the role of white blood cells in mediating wound remodeling. Because the mechanical microenvironment of cells is so dissimilar in Acomys and Mus animals, we cannot investigate these hypotheses in vivo. Here, we control the mechanical microenvironment independent of cellular matrix production by applying mechanical stretch stimuli through 2D silicone membranes or compliant hydrogels bound to the silicone with custom methods. Molecular biology assays and protein expression analyses will help us determine which cell types are responding to mechanical signals through which pathways. Development of a model to control fibrosis may be one of the secrets to successful regeneration in mammals.
