You are hereFebruary 18, 2019
Study provides insight into cell replacement therapies to treat Muscular Dystrophy
MINNEAPOLIS, MN (US), February 2019 – Researchers from the University of Minnesota Medical School have collaborated to gain a deeper understanding of the cells generated in vitro for the purpose of muscle regeneration.
Rita Perlingeiro, Ph.D., professor in the Department of Medicine and member of the Lillehei Heart Institute, Stem Cell Institute and Wellstone Muscular Dystrophy Center, pioneered the development of muscle stem/progenitor cells from pluripotent stem cells in vitro. These cells are able to generate new functional muscle upon transplantation into mice with muscular dystrophy, and also populate the new muscle with muscle stem cells also derived from the pluripotent stem cells. This allows that new muscle to repair itself if it is injured.
Now, the researchers have advanced their findings to identify for the first time the molecular signature of muscle stem cells generated in the dish, compared to that of the newly generated muscle stem cells in the newly formed muscle. They also compared these profiles to muscle stem cells isolated from mice at different developmental stages (embryonic, fetal, neonatal and adult).
These studies revealed that muscle cells generated in the dish are embryonic in nature; however, upon transplantation, the stem cell population they provide to the new muscle changes remarkably to a post-natal molecular signature, resembling neonatal and adult stem cells.
“While the engrafted muscle stem cells did not look identical to adult muscle cells, they no longer looked like embryonic cells either, which tells us they are changing after they are transplanted into the muscle environment,” said co-author Tania Incitti, a postdoctoral associate in Dr. Perlingeiro’s lab. The investigators also re-transplanted the engrafted muscle stem cells and found that very small numbers of the cells had tremendous potential for muscle regeneration upon secondary transplantation.
“We now are asking — what are the environmental cues that are changing our cells? We wanted to know more about the cells we have been working on for the last 10 years,” Dr. Perlingeiro said. “This study brings us more knowledge about the mechanism behind their tremendous regenerative potential.
“We knew that new muscle stem cells were present after transplantation, but understanding what role the environment plays and understanding that the cells are truly reshaped by exposure to muscle environment is an exciting finding,” she added.
“Knowledge at the molecular and functional level of what happens to these cells upon transplantation is particularly important to provide the rationale for future therapeutic applications.”
Their study is published in PNAS.