Molecular regulation of muscle repair recapitulates the mechanisms operating in embryonic organogenesis. Namely, the evolutionary conserved Notch and Wingless (Wnt) molecular pathways regulate the cell-fate determination of the stem and progenitor cells in adult skeletal muscle regenerating after injury. Recent data strongly suggest that the decline in regeneration-specific signaling and deteriorated regenerative potential are not irreversible signatures of stem-cell aging. In contrast, I found that the aged stem cell exposed to a young systemic milieu up-regulated the regeneration-specific genes and successfully repaired the damaged old tissues. The identification and characterization of systemic factors, which are altered by age and influence stem cell regenerative potential are the top priority projects that are being pursued in my laboratory at UC Berkeley. The candidate age-related factors that modulate the efficiency of muscle repair via their effect on the key Delta-Notch signaling, will be discussed. The mechanism by which the systemic milieu influences aging and regeneration is another top research focus of my laboratory. A perusal of the genetic aging models and recent data from my laboratory suggest that the efficiency of DNA repair in myogenic progenitor cells is strongly determined by the age of the systemic milieu. These data provide a potential molecular mechanism of the dominance of the systemic environment over the stem cell behavior.
Yet another approach pursued in my laboratory combines expertise in stem cell biology and bioengineering with a goal to provide muscle stem cells with a supportive microenvironment. The abilities of modified extra-cellular matrix (ECM) gels to promote geometrically controlled satellite cell expansion and differentiation will be presented. This work may serve as a general model to engineer synthetic cellular niches to optimally control and harness the regenerative potential of stem cells.