NOVEMBER 14TH, 2023POSTED BY UC IRVINE

One disorder the Hicks lab hopes to treat with their lab-grown muscle progenitors is tears to the rotator cuff muscles, which affects up to 30% of people over the age of 65. (Credit: Getty Images)

Researchers have identified a gene expressed during regeneration that is critical for muscle repair.

The key human skeletal muscle gene was also found in a subset of muscle fibers that were able to support human muscle stem cells after transplantation.

Although skeletal muscle is one of the most regenerative organ systems, there exists a need to improve regeneration for the more than 400 chronic muscle disorders and injuries that present clinically, including rotator cuff injuries and certain muscle disorders like Duchenne Muscular Dystrophy (DMD) or congenital muscular dystrophy.

The study appears in the journal Nature Cell Biology. Michael H. Hicks, assistant professor in the department of physiology and biophysics at the University of California, Irvine School of Medicine, is the co-corresponding author of the study, along with April D. Pyle, professor in the department of microbiology, immunology, and molecular genetics at UCLA.

“With our discovery, the development of ‘muscle in a dish’ is one step closer to reality,” says Hicks. “We’ve been researching this for years, and it’s implication for treating disease and muscle disorders and tears are immense.”
MUSCLE REPAIR

When confronted with an injury, our muscles naturally do a good job at repairing themselves. However, in severe injuries and genetic muscular diseases the muscle is unable to meet the demands of regenerating new tissues. Researchers say one solution is to take the cells from a dish and replicate how a healthy human body repairs muscle as newly generated muscle made in a lab can support stem cells better than the exhausted muscle tissue.

One disorder the Hicks lab hopes to treat with their lab-grown muscle progenitors is tears to the rotator cuff muscles, which affects up to 30% of people over the age of 65.

Damage to the rotator cuff muscles and tendon result in loss of mobility, prolonged hospitalization, and increased dependency on health care providers. Even after surgical attachment of the rotator cuff tendon to the bone, the muscle often fails to regenerate or incompletely regenerates, leading to decreased function.
STEM CELL NICHES

Hicks has funding from the UCI Anti-Cancer Challenge to use his approach for muscle reconstruction after radiation therapy for cancer survivors.

“Muscle stem cells are exposed to significant doses of radiation during radiotherapeutic management of cancer,” says Hicks. “The use of ionizing radiation has the potential to damage muscle stem cells and limit the recovery of muscle mass following disuse or overtime with age.”

Muscle stem cells are supported within anatomically defined specialized compartments, termed niches, that regulate their balance of self-renewal and differentiation over a person’s lifetime. The ability to establish new stem cells niches is essential for long-term cell therapies, in which transplanted muscle stem cells must balance the formation of new muscle fibers and maintain the stem cell pool to respond to future injuries.

Researchers demonstrated the formation of regenerating human myofibers following transplantation are a key source of niche emergence from transplanted human cells, which has previously been overlooked.

“This subset of regenerating muscle fibers resulted in a 50-fold better ability to support transplanted muscle progenitor cells,” said Pyle. “It would be interesting to determine whether myofibers in homeostasis or in disease settings