Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

U of M Researchers Utilize Genetically Corrected Stem Cells to Spark Muscle Regeneration

Published: Monday, July 22, 2013
Last Updated: Monday, July 22, 2013
Bookmark and Share
Research is published in Nature Communications.

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.

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

Perlingeiro’s technology involves giving pluripotent cells a short pulse of a muscle stem cell protein called Pax3. The Pax3 protein pushes the pluripotent cells to become muscle stem cells, and allows them to be expanded exponentially in number. The Pax3-induced muscle stem cells were then transplanted back into the same strain of muscular dystrophy mice from which the pluripotent stem cells were originally derived.

Combined, the platforms created muscle-generating stem cells that would not be rejected by the body’s immune system. According to Perlingeiro, the transplanted cells performed well in the dystrophic mice, generating functional muscle and responding to muscle fiber injury.

“We were pleased to find the newly formed myofibers expressed the markers of the correction, including utrophin,” said Perlingeiro, a Lillehei endowed scholar within the Lillehei Heart Institute and an associate professor in the University of Minnesota Medical School. “However, a very important question following transplantation is if these corrected cells would self-renew, and produce new muscle stem cells in addition to the new muscle fibers.”

By injuring the transplanted muscle and watching it repair itself, the researchers demonstrated that the cell transplants endowed the recipient mice with fully functional muscle stem cells.

This latest project from the U of M provides the proof-of-principle for the feasibility of combining induced pluripotent stem cell technology and genetic correction to treat muscular dystrophy.

“Utilizing corrected induced pluripotent stem cells to target this specific genetic disease proved effective in restoring function,” said Antonio Filareto, Ph.D., a postdoctoral fellow in Perlingeiro’s laboratory and the lead author on the study. “These are very exciting times for research on muscular dystrophy therapies.”

These studies pave the way for testing this approach in reprogrammed human pluripotent cells from muscular dystrophy patients.

According to Perlingeiro, “Developing methods to genetically repair muscular dystrophy in human cells, and demonstrating efficacy of muscle derived from these cells are critical near-term milestones, both for the field and for our laboratory. Testing in animal models is essential to developing effective technologies, but we remained focused on bringing these technologies into use in human cells and setting the stage for trials in human patients.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,000+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

U of M Researchers Discover Link Between Heart, Blood, and Skeletal Muscle
Gene thought to make heart tissues turns out to make blood and muscles as well.
Tuesday, May 07, 2013
New Muscular Dystrophy Treatment Approach Developed Using Human Stem Cells
New process makes the production of human muscle cells from stem cells efficient and effective.
Wednesday, May 09, 2012
U of M Researchers Improve Method to Create Induced Pluripotent Stem Cells
By fusing Oct4 and MyoD proteins researchers succeeded in “powering up” the stem cell regulator, which improve the efficiency and purity of reprogrammed iPS cells.
Tuesday, July 26, 2011
U of M Performs First Systemic Therapy for Fatal Childhood Disease
Doctors have performed the first bone marrow and cord blood transplant to treat genetic skin disease.
Thursday, November 08, 2007
University of Minnesota Finds Cell in Adult Heart with Embryonic Stem Cell Capability
Researchers at the University of Minnesota have found a cell type in adult rat heart tissue that can make all types of cardiac cells.
Tuesday, January 23, 2007
Scientific News
Stem Cell ‘Heart Patch’ Almost Perfected
Scientists aiming to perfect and test 3D "heart patches" in animal model, last hurdle before human patients.
Stem Cells Growing 3D Lung-in-a-Dish
Researchers have created 3D lung-like tissue from lung-derived stem cells. The tissue can be used to study lung diseases.
MRI Guidance Aids Stem Cell Delivery
Scientists have delivered stem cells to the brain with unprecedented precision, infusing the cells under real-time MRI guidance.
Mechanisms of Parkinson’s Pathology
Defects that lead to cells’ failure to decommission faulty mitochondria cause nerve cells to die, triggering the symptoms of Parkinson’s disease.
Stem Cell Transplant Without Radiation or Chemotherapy
Researchers have successfully performed stem cell transplants without using radiation or chemotherapy.
Advanced Lymphoma in Remission After T-Cell Therapy
63% of trial participants who recieved two-drug combination chemo plus intermediate dose of engineered T cells went into complete remission.
Inherited Heart Condition Breakthrough
Using stem cells, scientists have created a specific heart condition model, yeilding insights into unexpected disease mechanisms.
Biobank Storage Time Affects Blood Test Results
Study finds storage time of blood samples at a biobank may affect test results as much as patient age.
Transplanted Stem Cells Age Cells by 30 Years
Research suggests stem cell transplants are linked to an increase in immune cell's “molecular age” from blood cancer patients.
Commanding Stem Cells to Build Bone
Natural molecule can coax stem cells into regenerating bone tissue, researchers have discovered.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!