Stem Cell Preconditioning and Transplantation as a Therapeutic Strategy to Revitalize Growth and Function in Aged Skeletal Muscle
Aging is associated with decreased regenerative potential as well as greater susceptibility to damage and reduced anabolic response to factors that stimulate skeletal muscle maintenance and growth. With numerous mechanisms involved such as decreased growth factor (GF) levels, dennervation and declining vascular supply, developing effective therapeutic strategies for the age-related loss of muscle mass and function has proven to be a considerable challenge. Recently our lab has isolated and characterized a population of muscle-derived Mesenchymal Stem Cells (mMSCs). We have demonstrated that preconditioning these multipotent cells with mechanical strain in vitro enhances their ability to secrete GFs and stimulate muscle, vessel, and neuronal growth in young mice. It is unknown however, if mMSC transplantation would provide a viable therapy for age-related muscle loss. With many systems displaying deficits that contribute to loss of muscle mass and function a multifactorial, multisystem approach is likely needed. Using a PDMS based cell culture system that closely mimics the aged skeletal muscle microenvironment and aged animal models the focus of my research is to understand how the mechanical environment regulates stem cell behavior with the long term goal of elucidating key mechanisms and translating them into more effective prevention and treatment strategies for age-related loss of muscle mass and function.