A technique called somatic-cell nuclear transfer
(cloning) has been applied to human oocytes, resulting in the generation of
personalized stem cells, albeit genetically abnormal ones.
A team of scientists led by Dieter Egli
and Scott Noggle at The New York Stem Cell Foundation (NYSCF) Laboratory in New
York City have made an important advance in the development of patient-specific
stem cells that could impact the study and treatment of diseases such as
diabetes, Parkinson’s, and Alzheimer’s. As reported in today’s Nature, for the
first time the scientists have derived embryonic stem cells from individual
patients by adding the nuclei of adult skin cells from patients with type-1 diabetes
to unfertilized donor oocytes. However, this technique creates triploid human pluripotent
stem-cell lines.
The achievement is significant because
such patient-specific cells potentially can be transplanted to replace damaged
or diseased cells in persons with diabetes and other diseases without rejection
by the patient’s immune system. The scientists report further work is necessary
before such cells can be used in cell-replacement medicine.
The research was conducted in The NYSCF
Laboratory in Manhattan in collaboration with clinicians and researchers at
Columbia University Medical Center. DNA analysis was provided by scientists at
the University of California, San Diego.
“The
specialized cells of the adult human body have an insufficient ability to
regenerate missing or damaged cells caused by many diseases and injuries,” said Dr. Egli, NYSCF senior scientist in the study.
“But
if we can reprogram cells to a pluripotent state, they can give rise to the
very cell types affected by disease, providing great potential to effectively
treat and even cure these diseases. In this three-year study, we successfully
reprogrammed skin cells to the pluripotent state. Our hope is that we can
eventually overcome the remaining hurdles and use patient-specific stem cells
to treat and cure people who have diabetes and other diseases.”
“The
ultimate goal of this study is to save and enhance lives by finding better
treatments and eventually cures for diabetes, Alzheimer’s, Parkinson’s and
other debilitating diseases and injuries affecting millions of people across
the US and the globe,” said NYSCF CEO Susan L. Solomon.
“This
research brings us an important step closer to creating new healthy cells for patients
to replace their cells that are damaged or lost through injury.”
The scientists demonstrate for the
first time that the transfer of the nucleus from an adult skin cell of a
patient into an oocyte without removing the oocyte nucleus results in
reprogramming of the adult nucleus to the pluripotent state. Embryonic stem
cell lines were then derived from the oocyte containing the patient’s genetic
material.
Since these pluripotent stem cells also
have a copy of the chromosome from the oocyte, resulting in an abnormal number
of chromosomes, these cells are not ready for therapeutic use. Future work will
focus on understanding the role of the oocyte chromosome so that patient
specific stem cells can be made that contain only the patient’s DNA.
In the study, skin cells from patients
with type-1 diabetes and healthy patients (control group) were reprogrammed,
allowing the derivation of pluripotent stem cells, cells that have the capacity
for universal tissue production. Such cells potentially could be used to create
beta cells that produce insulin.
Patients with type 1 diabetes lack
insulin-producing beta cells, resulting in insulin deficiency and high blood
sugar levels. Producing beta cells from stem cells for transplantation holds promise
for the treatment and potential cure of type-1 diabetes.
“This
is an important step toward generating stem cells for disease modeling and drug
discovery, as well as for ultimately creating patient-specific cell-replacement
therapies for people with diabetes or other degenerative diseases or injuries,” said Rudolph L. Leibel, MD, co-director of Columbia’s Naomi Berrie
Diabetes Center and a collaborator in the study.
The study raises the possibility of
using somatic cell reprogramming to create banks of stem cells that could be
used for a wide range of patients, noted another collaborator, Robin Goland, MD,
co-director of the Naomi Berrie Diabetes Center.
“In
theory, stem cell lines could be matched to a particular patient, much as we do
now when we screen an individual for compatibility with a kidney transplant,” she said.
“This
project is a great example of how enormous strides can be achieved when
investigators in basic science and clinical medicine collaborate,” said Mark V. Sauer, MD, a coauthor of the paper and Vice Chairman
of the Department of Obstetrics and Gynecology and chief of reproductive
endocrinology at Columbia University Medical Center. Dr. Sauer is also program director
of assisted reproduction at the Center for Women’s Reproductive Care.
“I
feel fortunate to have been able to participate in this important project.”
Zach W. Hall, PhD, former Director of
the NIH’s National Institute of Neurological Disorders and Stroke and former
President of the California Institute for Regenerative Medicine said:
“This
work represents a major advance toward the production of patient-specific stem
cells for therapeutic use by demonstrating that the nucleated oocyte has the
ability to completely reprogram the nucleus of an adult human cell.”
The study was funded solely with
private funding and adhered to ethical guidelines adopted by the American
Society for Reproductive Medicine and the International Society for Stem Cell Research,
as well as protocols reviewed and approved by the institutional review board
and stem cell committees of Columbia University.
The New York Stem Cell Foundation (NYSCF) conducts advanced stem cell research in its own laboratory
and supports research by stem cell scientists at other institutions around the world.
More information is available at www.nyscf.org.
Columbia University Medical Center (CUMC) provides international leadership in basic, pre-clinical and
clinical research, in medical and health sciences education, and in patient
care. More information is available at www.cumc.columbia.edu.
Source:
New York Stem Cell Foundation
Contact:
Diane Mathis Marr
Reference:
Human oocytes reprogram somatic cells to a pluripotent state Scott Noggle, Ho-Lim Fung, Athurva Gore, Hector Martinez, Kathleen Crumm Satriani, Robert Prosser, Kiboong Oum, Daniel Paull, Sarah Druckenmiller, Matthew Freeby, Ellen Greenberg, Kun Zhang, Robin Goland, Mark V. Sauer, Rudolph L. Leibel & Dieter Egli
Nature 478, 70–75 (06 October 2011), doi:10.1038/nature10397
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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/
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