Engineering Myoblasts for Transplantation
DESCRIPTION (provided by applicant): The primary goals of stem cell biology are to develop practical cell-based tools: 1) to enhance the repair of damaged organs and tissues; and 2) as vehicles for gene therapy to introduce engineered genes to the body to either correct a genetic defect or to provide therapeutic molecules.
The use of embryonic stem cells is both controversial and fraught with technical limitations that restrict their current use in a therapeutic setting. In contrast, the use of adult-derived, lineage-specific stem cells is currently the focus of several clinical trials. For example, two clinical trials are under way to assess the value of autologous muscle satellite cell transplantation to improve myocardial function following infarction. Since congestive heart failure accounts for more than 43% of Medicare's annual expenditures, the market for this therapy is substantial.
Satellite cells are a resident population of muscle stem cells that can be harvested from virtually any patient with a simple needle biopsy. These cells can be expanded in vitro and then reintroduced in vivo to either repair tissues such as damaged myocardium or skeletal muscle, or instead engineered to express ectopic genes that are of therapeutic value. One of the major hurdles limiting the utility of myoblasts for transplantation is that relatively few of these cells survive past the first few days.
We have identified a novel gene that plays a key regulatory role in the myoblast survival and differentiation in mammals. We have also demonstrated that expression of a dominant-negative form of this gene allows myoblasts to survive in the absence of trophic support, thus making it an ideal target for developing cell-based therapies. In this Phase I SBIR project, we will: 1) optimize methods for targeting the function of this protein in primary mouse myoblasts, and 2) determine if these engineered cells survive and contribute to muscle function in vivo.
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Research Institution Information:
BIOMEDICAL RESEARCH MODELS, INC.
BIOMEDICAL RESEARCH MODELS, INC. 67 MILLBROOK, ST, STE 422 WORCESTER, MA 01606
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UNIVERSITY OF MASSACHUSETTS AMHERST
GRANT & CONTRACT ADMINISTRATION
Amherst, MA 01003
Nonprofit college or university