SUMMARY:
UCLA researchers in the Department of Bioengineering have developed a novel chemical cocktail for enhancing myogenic stem cell expansion both in vitro and in situ that could lead to more affordable and faster development of stem cell-based therapies and chemical delivery technologies for muscle regeneration.
BACKGROUND:
Skeletal muscle tissue serves numerous physiological functions, extending beyond locomotion to diverse vital processes such as regulating metabolism and body temperature. When injuries occur, skeletal muscles can activate resident myogenic stem cells to divide and repair the damaged tissue. However, traumatic injuries, such as severe muscle loss after traffic accidents, or progressive muscle loss associated with aging and genetic diseases, can compromise the regenerative capability of skeletal muscles, resulting in disability and poor quality of life. In the U.S., musculoskeletal diseases, including trauma and arthritis, affect more than half of adults age 18 and over. As the U.S. population is aging, musculoskeletal diseases are becoming a greater burden every year. Muscle stem cell-based therapies provide promising strategies for improving skeletal muscle regeneration. However, challenges remain in making these therapies clinically feasible, namely the scarcity of cell sourcing and the lack of an effective method to proliferate myogenic stem cells. Thus, finding methods to selectively and efficiently expand myogenic stem cells in muscle could transform treatment for musculoskeletal injuries and diseases.
The generation of skeletal muscle tissue in vitro has also enabled the rapid emergence of cultured meat technologies. As the global population increases, demand for meat proteins is projected to increase beyond what traditional livestock agriculture can supply. Diversifying methods for protein production will thus be criticl for increasing the resiliency of our food systems. Novel, scalable, and cost-effective methods for expanding myogenic stem cells in muscle could help make cultured meat commercially feasible.
INNOVATION:
UCLA researchers led by Dr. Song Li in the Department of Bioengineering have developed a chemical cocktail that can efficiently induce and expand myogenic stem cells from dermal cells and skeletal muscle stem cells for skeletal muscle repair. To test efficacy of the cocktail, the researchers used RT-PCR and immunofluorescence to confirm specific upregulation of myogenic markers. After successful expansion of myogenic stem cells in vitro, they demonstrated that upon transplantation, the injected stem cells successfully engrafted to repair pre-injured tibialis anterior muscles in adult and aged mouse models as well as in mouse models of Duchenne muscular dystrophy. The researchers also demonstrated that nanoparticle delivery of the chemical cocktail induces a robust response in situ activation and expansion of satellite cells in adult and aged mouse models. Taken together, this chemical cocktail provides a novel and clinically feasible approach to harnessing and maximizing the regenerative potential of sourced and resident cells to accelerate and promote muscle regeneration.
POTENTIAL APPLICATIONS:
• Provides a rich source of myogenic stem cells using efficient and specific in vitro expansion from dermal cells or skeletal muscle stem cells
• An in situ muscle regeneration therapy via a nanoparticle-based delivery system
• Muscle cell expansion in the food industry
ADVANTAGES:
• Expanded myogenic stem cells show high efficacy of engraftment
• Skin dermal cells can be conveniently isolated via minimally invasive procedures
• Promotes in vitro and in situ expansion of satellite cells
• Cocktail-treated muscles showed faster and better regeneration with lower number of macrophages
DEVELOPMENT-TO-DATE:
The researchers have successfully validated that their cocktail enhances expansion of myogenic stem cells and demonstrated its utility both in vitro and in situ in adult, aged, and Duchenne muscular dystrophy mouse models.