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

Chromosome Therapy to Correct a Severe Chromosome Defect

Published: Tuesday, January 14, 2014
Last Updated: Tuesday, January 14, 2014
Bookmark and Share
Induced pluripotent stem cell reprogramming offers potential to correct abnormal chromosomes.

Geneticists from Ohio, California and Japan joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study, published online January 12, 2014 in Nature, used stem cells to correct a defective “ring chromosome” with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations.

“In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome,” said senior author Anthony Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and chair of Case Western Reserve School of Medicine Department of Genetics and Genome Sciences and University Hospitals Case Medical Center.

Wynshaw-Boris led this research while a professor in pediatrics, the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC San Francisco (UCSF) before joining the faculty at Case Western Reserve in June 2013.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The prospect for effective countermeasures has evaded scientists — until now. The international research team discovered the potential for substituting the malfunctioning ring chromosome with an appropriately functioning one during reprogramming of patient cells into induced pluripotent stem cells (iPSCs). iPSC reprogramming is a technique that was developed by Shinya Yamanaka, MD, PhD, a co-corresponding author on the Nature paper. Yamanaka is a senior investigator at the UCSF-affiliated Gladstone Institutes, a professor of anatomy at UCSF, and the director of the Center for iPS Cell Research and Application (CiRA) at theInstitute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University. He won the Nobel Prize in Medicine in 2012 for developing the reprogramming technique.

Marina Bershteyn, PhD, a postdoctoral fellow in the Wynshaw-Boris lab at UCSF, along with Yohei Hayashi, PhD, a postdoctoral fellow in the Yamanaka lab at the Gladstone Institutes, reprogrammed skin cells from three patients with abnormal brain development due to a rare disorder called Miller-Dieker Syndrome, which results from large terminal deletions in one arm of chromosome 17. One patient had a ring chromosome 17 with the deletion, and the other two patients had large terminal deletions in one copy of chromosome 17, but not a ring. Additionally, each of these patients had one normal chromosome 17.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, the researchers reprogrammed cells from two different patients that each had ring chromosome 13. These reprogrammed cells also lost the ring chromosome, and contained a duplicated copy of the normal chromosome 13.

“It appears that ring chromosomes are lost during rapid and continuous cell divisions during reprogramming,” Yamanaka said. “The duplication of the normal chromosome then corrects for that lost chromosome.”

“Ring loss and duplication of whole chromosomes occur with a certain frequency in stem cells,” explained Bershteyn. “When chromosome duplication compensates for the loss of the corresponding ring chromosome with a deletion, this provides a possible avenue to correct large-scale problems in a chromosome that have no chance of being corrected by any other means.”  

“It is likely that our findings apply to other ring chromosomes, since the loss of the ring chromosome occurred in cells reprogrammed from three different patients,” Hayashi said.

According to Wynshaw-Boris, “In theory, the way you could potentially correct a chromosome with deletions or duplications is to make a ring out of it and then get rid of the ring chromosome during reprogramming. Ring chromosomes are quite rare, but chromosome abnormalities are much more common and cause a variety of severe birth defects. So far, it is only possible to do this chromosome therapy for cells in culture, not in human beings. However, it may be useful to use this for tissue repair of birth defects and other abnormalities found in individuals with chromosomal abnormalities as techniques for regenerative medicine are developed in the future.”

Other collaborators on the paper included Guillaume Desachy, M.Sc., Edward C. Hsiao, MD, Salma Sami, Kathryn M. J. Tsang, and Lauren A. Weiss, PhD, of UCSF; and Arnold R. Kriegstein, MD, PhD of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Further Information
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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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 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

Stem Cell Survival Strategy Is Key to Blood and Immune System Health
Stem cells of the aging bone marrow recycle their own molecules to survive and keep replenishing the blood and immune systems as the body ages.
Monday, February 18, 2013
UCSF Receives $2 Million to Advance UC-Wide Biobanking Initiative
Goal of the project is to develop an ethical, efficient and sustainable system for obtaining, processing and sharing biospecimens and data.
Thursday, November 15, 2012
Gladstone Scientists Use Stem Cell Technology to Tackle Huntington’s Disease
International consortium uses patient cells to develop a human model of Huntington’s disease in a dish to improve and speed drug development.
Monday, July 02, 2012
Gladstone Scientists Reprogram Skin Cells into Brain Cells
Innovative technique lays groundwork for novel stem cell therapies.
Monday, June 11, 2012
Scientific News
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
CRI Identifies Emergency Blood-formation Response
Researchers report that when tissue damage occurs, an emergency blood-formation system activates.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
Promise of Newborn Stem Cells to Revolutionize Clinical Practice
In this article Shweta Sharma, PhD, discusses the potential of an Umbilical Cord Blood bank as an untapped source of samples for research and clinical trials.
The Life Story of Stem Cells
A model analyses the development of stem cell numbers in the human body.
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Advancing Genome Editing of Blood Stem Cells
Genome editing techniques for blood stem cells just got better, thanks to a team of researchers at USC and Sangamo BioSciences.
Skyscraper Banner

Skyscraper Banner
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos