Distinct Stem Cell Protein May Play Critical Role in Regenerating Muscle

MINNEAPOLIS, June 27, 2017 – A new study published in the journal Cell Reports brings researchers one step closer to a stem cell therapy for skeletal muscle regeneration, a possible approach to treating conditions like muscular dystrophy.

Researchers from the University of Minnesota Medical School investigated a key protein called PAX7 that turns pluripotent stem cells (PSC) into skeletal muscle stem cells, which go on to develop into healthy mature muscle tissue. The investigators then catalogued all the sites in the human genome to which the PAX7 protein binds. Some of the genes bound and switched on by PAX7 proteins appear on the surface of the cell, the researchers found, and can be used as markers to purify those muscle-producing cells from PSCs that developed into other cells.

“Regenerative medicine based on the use of pluripotent stem cells can only progress to the clinic if selective cell expansion strategies are accompanied by purification of the key cell types,” said Rita Perlingeiro, Ph.D., professor in the University of Minnesota Medical School and member of the Masonic Cancer Center, University of Minnesota. “This is critical because pluripotent stem cells can turn into anything.”

Previous work relied on the use of a glowing fluorescent protein for the purification of these cells, which cannot be safely used in patients. But Perlingeiro, along with University colleagues Alessandro Magli, Ph.D. and Tania Incitti, Ph.D., show cells purified with these markers are able to rebuild diseased skeletal muscle in a way more suitable in patients. 

“Injecting diseased muscle with improper cell populations can make the disease worse,” Perlingeiro added. “This purification method represents an important advancement toward bringing stem cell therapy for muscle disease to the clinic, where it can benefit patients and parents who are fighting muscular dystrophy.”

This project was supported by NIH grants R01 AR055299, U01 HL100407R01, the Greg Marzolf Jr Foundation, ADVault Inc., MyDirectives.com, and Regenerative Medicine Minnesota. The cytogenetic analyses were performed in the Cytogenomics Shared Resource at the University of Minnesota with support from the comprehensive Masonic Cancer Center NIH Grant #P30 CA077598-09.