U of M researchers utilize genetically corrected stem cells to spark muscle regeneration

Public release date: 5-Mar-2013 [ | E-mail | Share ]

Contact: Caroline Marin crmarin@umn.edu 612-624-5680 University of Minnesota Academic Health Center

MINNEAPOLIS/ST. PAUL (March 5, 2013) Researchers at the University of Minnesota's Lillehei Heart Institute have combined genetic repair with cellular reprogramming to generate stem cells capable of muscle regeneration in a mouse model for Duchenne Muscular Dystrophy (DMD).

The research, which provides proof-of-principle for the feasibility of combining induced pluripotent stem cell technology and genetic correction to treat muscular dystrophy, could present a major step forward in autologous cell-based therapies for DMD and similar conditions and should pave the way for testing the approach in reprogrammed human pluripotent cells from muscular dystrophy patients.

The research is published in Nature Communications.

To achieve a meaningful, effective muscular dystrophy therapy in the mouse model, University of Minnesota researchers combined three groundbreaking technologies.

First, researchers reprogrammed skin cells into "pluripotent" cells cells capable of differentiation into any of the mature cell types within an organism. The researchers generated pluripotent cells from the skin of mice that carry mutations in the dystrophin and utrophin genes, causing the mice to develop a severe case of muscular dystrophy, much like the type seen in human DMD patients. This provided a platform that would mimic what would theoretically occur in human models.

The second technology employed is a genetic correction tool developed at the University of Minnesota: the Sleeping Beauty Transposon, a piece of DNA that can jump into the human genome, carrying useful genes with it. Lillehei Heart Institute researchers used Sleeping Beauty to deliver a gene called "micro-utrophin" to the pluripotent cells they were attempting to differentiate.

Much like dystrophin, human micro-utrophin can support muscle fiber strength and prevent muscle fiber injury throughout the body. But one key difference between the two is in how each is perceived by the immune system. Because dystrophin is absent in muscular dystrophy patients, its presence can prompt a devastating immune system response. But in those same patients, utrophin is active and functional, making it essentially "invisible" to the immune system. This invisibility allows the micro-utrophin to replace the dystrophin and progress the process of building and repairing muscle fiber within the body.

The third technology utilized is a method to produce skeletal muscle stem cells from pluripotent cells a process developed in the laboratory of Rita Perlingeiro, Ph.D., the principal investigator of the latest study.

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U of M researchers utilize genetically corrected stem cells to spark muscle regeneration