Integrative Stem Cell Engineering Strategies to Rejuvenate Aging Skeletal Muscle

Young Jang, Ph.D.
School of Biological Sciences
Georgia Institute of Technology

ABSTRACT
Age-related loss of muscle mass and function often referred to as sarcopenia dramatically affects the quality of life in the elderly population and predisposes them to an increased risk of morbidity, disability, and mortality. As the elderly population rapidly grows in the United States, the healthcare cost to treat sarcopenia and frailty-related is projected to grow exponentially in the next decades. The etiology of sarcopenia is a multifactorial process that involves both intrinsic and extrinsic factors. However, mounting evidence from both animal and human studies suggests a decline in muscle stem cell (MuSC) function and an inability to repair/regenerate muscle following injury directly contributes to age-acquired deficits in muscle function. Although stem cell interventions and cell-based therapeutic approaches seemed promising to treat age-dependent muscle wasting, only limited success has been achieved due to extremely low donor stem cell engraftment and survival in the aged host muscle. Consequently, there is a growing need for a clinically applicable therapeutic strategy to attenuate age-related muscle loss. To overcome this challenge, we engineered a biofunctional matrix that harnesses key characteristics of native muscle microenvironment and maximizes MuSCs myogenic potential. By capitalizing MuSC delivery in the biomimetic matrix, I will discuss some of the strategies we can use to understand the mechanisms of sarcopenia and describe advanced stem cell niche-based therapy that rejuvenates aging muscle. In the second part of the presentation, I will discuss how heterochronic parabiosis, in which young and aged animals are surgically attached to share circulation, and how exposure of aged muscle, to a “youthful” systemic environment, reverse many indicators of age-related pathology and restores robust muscle regeneration after injury. I will also describe how we can leverage the organ-on-a-chip and functional biomaterials to mimic parabiosis and understand the systemic regulations of muscle aging and other muscle-wasting conditions.