Characterization of Human Skeletal Muscle Stem Cells for Clinical Application

Characterization of Human Skeletal Muscle Stem Cells for Clinical Application

Funding Type: 
New Faculty Physician Scientist
Grant Number: 
RN3-06504
Approved funds: 
$3,084,000
Disease Focus: 
Skeletal Muscle
Stem Cell Use: 
Adult Stem Cell
Public Abstract: 
Skeletal muscle makes up 40% of our bodies, dictates our form, is responsible for our ability to move, express ourselves, eat, breath and to look around. Restoration or preservation of the body’s normal form and function is the central goal of regenerative medicine and the central focus of my clinical specialty of plastic and reconstructive surgery. Skeletal muscle injury and disease are major sources of morbidity that affect millions. The potential for treating these ailments with regenerative approaches that use stem cells is enormous because skeletal muscle naturally has its own stem cell population. However, to make human muscle stem cells a usable clinical tool we need to be able to characterize them, transplant them, and induce them to function effectively. To accomplish these goals, our objectives are to identify appropriate human muscles to harvest stem cells from, to develop techniques to transplant them, and to test them in models of diseases. This work is expected to lead directly to treatments for patients with several disabling muscle degenerative conditions that affect small but critical muscles that could be regenerated with localized muscle stem cell transplants. Examples include facial paralysis or loss of hand function, and conditions affecting the eye muscles causing vision loss. This work also lays the groundwork for tissue engineering of muscles, and will contribute to approaches to correct genetic muscle defects or treat other systemic muscle diseases.
Statement of Benefit to California: 
Skeletal muscle injury and disease are major sources of morbidity that affect Californians of all ages, including the veteran population. Regenerative medicine and stem cell biology offer great potential for opportunities to improve upon current treatments and to develop approaches for many of the muscle ailments that remain essentially untreatable. Skeletal muscle stem cells have been well characterized in mice, and preliminary evidence suggests similar approaches in humans will enable clinical translation. Therefore, the proposed research seeks to develop stem cell therapies that will directly impact muscle ailments that are at the root of diverse deformities and disabilities of the face, body and limbs. California is the birthplace of many of the great advances in reconstructive surgery, including microsurgery and muscle flaps, largely through the support of its people, and their pioneering spirit. In turn, Californians have benefited and continue to benefit from the newest and best approaches that reconstructive surgery has to offer. We propose to continue to improve reconstructive and regenerative options for the citizens of California by building on our strong historical foundation to address current needs. Our research will carry on this tradition because of our focus on problems of form and function affecting many of our citizens, the logical path to muscle stem cell clinical application, and the unique clinical and scientific focus and potential of our team.
Progress Report: 

Year 1

In the first year of the New Faculty Physician Scientist award, my colleagues and I have made progress on all 3 Aims. The majority of our focus in accordance with our planned timeline has been on Aim 1, where we have made the most significant progress and are preparing our first manuscript based on Aim 1 results. Aim 1 focuses on identification of appropriate donor muscles for human muscle stem cell applications. We are using the backdrop of knowledge that we have concerning mouse muscle stem cell biology to study human muscle stem cells. As human muscle stem cells have not been definitively characterized or transplanted, the initial main focus of this CIRM grant is to do so with stem cells from diverse muscles and, combined with our clinical understanding of expendability of different muscles, choose human muscles that will be appropriate to harvest stem cells from in future applications. For the experiments in Aim 2, we are testing injury and transplantation methods for human muscle stem cells that could potentially be used clinically. We have also begun work on Aim 3, developing preclinical models in which to test human muscle stem cell transplantation.

© 2013 California Institute for Regenerative Medicine