Year 2

We are pleased to report that we have been able to address all of the specific aims of the grant funded by CIRM. This progress goes a long way toward enabling therapies that will contribute to a substantially enhanced quality of life. The aging population is increasing in industrialized countries and aged-related muscular pathologies are becoming increasingly common leading to escalating medical costs and highly debilitating muscular weakness. It is well known that in young adults, skeletal muscle has a remarkable ability to heal itself and this capacity is solely due to the robust proliferative and differentiative potential of muscle stem cells. What is needed is a means of harnessing this stem cell potential by finding ways to increase stem cell numbers and function in cell culture for use in cell based therapies. This CIRM grant has enabled us to make progress that would otherwise not have been possible given the current NIH funding crisis. We are extremely grateful. Due to this grant we have succeeded in characterizing the functional differences between young and old muscle stem cells. Importantly, we have defined culture conditions that enable the maintenance, self-renewal, and expansion of muscle stem cells for the first time. (Aims 1 and 2). Finally, we have successfully applied our knowledge of adult mouse muscle stem cells to their human counterparts. We have identified markers for the prospective isolation of human muscle stem cells and growth conditions that allow their propagation in culture for cell based therapies (Aim3). Our findings have been well received with a seminal publication in Science this year and invitations to speak in symposia and at universities worldwide. Moreover our work was featured in the Wall Street Journal and on the front page of the New York Times in 2010. Another major advance in our laboratory, which was not part of this grant, was our development of the first mouse model that mimics the human genetic muscle wasting disease, Duchenne Muscular Dystrophy, which was published in Cell in 2010. Our future work will focus on testing muscle stem cell based therapies developed in the course of this grant in this muscle disease model. The findings will have relevance not only to DMD, but also more generally to sarcopenia and the profound muscle atrophy that accompanies aging.