Our studies will assess if donor skeletal muscle tissue (from human cadavers and mice) transplanted into host muscle through a novel Minimally Invasive Muscle Embedding (MIME) technique can promote donor-derived myogenesis. Our studies will also assess in neuromuscular electrical stimulation and forceful eccentric muscle contractions can enhance donor-derived myogenesis. We will perform our studies in immunodeficient NSG- GFP mice, which are not only good hosts for transplantation studies due to the low risk of immune rejection, but also because they express a green fluorescent protein (GFP) reporter in all their cells, making it easy to differentiate between host (GFP(+)) and donor-derived (GFP(-)) muscle fibers. We will assess donor-derived myogenesis through histological studies as well as physiological studies. If successful, our studies could have significant translational impact in the treatment of muscle loss arising from muscle disease and trauma. Our studies could also pave the way for a new line of research looking into the use of cadaveric muscle as a source of myogenic cells; provide important insights into the kinds of muscle activity needed to increase myogenesis from bioengineered muscle containing myogenic cells; and, also help in the development of animal models of human muscle disease where transplantation of human muscle into mouse is the approach of choice.

Public Health Relevance

Our proposed work will test if donor skeletal muscle tissue obtained from human cadavers and from mice can produce new muscle fibers when implanted into host mouse muscle. We will also test if certain types of exercise are capable of increasing the number, size and function of muscle fibers derived from muscle- generating cells present in donor muscle tissue.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD091648-02
Application #
9459949
Study Section
National Institute of Child Health and Human Development Initial Review Group (CHHD)
Program Officer
Nitkin, Ralph M
Project Start
2017-04-01
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Wayne State University
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202