Harvard Stem Cell Institute researchers have for the first time demonstrated that transplanted muscle stem cells can both improve muscle function in mice with a form of muscular dystrophy and replenish the stem cell population for use in the repair of future muscle injuries.
“I’m very excited about this,” said lead author Amy Wagers, PhD, HSCI Principal Faculty member. “This study indicates the presence of renewing muscle stem cells in adult skeletal muscle and demonstrates the potential benefit of stem cell therapy for the treatment of muscle degenerative diseases such as muscular dystrophy.”
Wagers’ findings are “extremely significant,” said HSCI Co-Director Douglas Melton, PhD. “This provides proof of concept for treating a degenerative condition by implanting stem cells.”
The study was designed to test the concept that skeletal muscle precursor cells could function as adult stem cells and that transplantation of these cells could both repair muscle tissue and regenerate the stem cell pool in a model of Duchenne muscular dystrophy. There are many forms of muscular dystrophy of which Duchenne muscular dystrophy is the most common. It is caused by a genetic mutation and is characterized by rapidly progressing muscle degeneration for which there is currently no cure.
The data from this new study demonstrates that regenerative muscle stem cells can be distinguished from other cells in the muscle by unique protein markers present on their surface. Wagers used these markers to select stem cells from normal adult muscle and transferred the cells to the diseased muscle of mice carrying a mutation in the same gene affected in human Duchenne muscular dystrophy.
“Once the healthy stem cells were transplanted into the muscles of the mice with muscular dystrophy, they generated cells that incorporated into the diseased muscle and substantially improved the ability of the treated muscles to contract,” said Wagers. “At the same time, the transplantation of the healthy stem cells replenished the formerly diseased stem cell pool, providing a reservoir of healthy stem cells that could be re-activated to repair the muscle again during a second injury.”
This two part solution demonstrated that these cells truly were stem cells as demonstrated by their ability to assist both in the immediate repair and in the follow-on repair, as a result of forming that “reserve pool” which can maintain muscle regenerative activity in response to future challenges.
In addition to showing that stem cell therapy could be beneficial for degenerative muscle diseases, this work will lead to other studies in the near-term that will identify pathways that regulate these muscle stem cells in order to understand ways to boost the normal regenerative potential of these cells. These could include drug therapies or genomic approaches. In the longer term, the goal will be to replicate these findings in humans.
“This is still very basic science, but I think we’re going to be able to move forward in a lot of directions. It opens up many exciting avenues,” said Wagers.