UK HealthCare Publications » Advances & Insights » General Health »
Download Printable PDF (770 KB)
Spurred by ethical issues surrounding human cloning and the use of embryonic stem cells, scientists have been in a furious race to discover new ways to obtain stem cells for research. In November, two independent teams on opposite sides of the globe achieved that goal by creating stem cells from human skin cells. The discovery is being hailed as a major breakthrough that could speed up the development of new drugs for a number of diseases and conditions.
The discovery is being hailed as a major breakthrough.
The discovery is being hailed as a major breakthrough.
Until recently, the only method of obtaining stem cells in the United States was through embryos created by in vitro fertilization, a controversial process that involves destruction of the embryo. A few countries allow researchers to clone embryos for that purpose.
In the two recent studies, research teams led by Dr. Shinya Yamanaka of Kyoto University in Japan and Dr. James Thomson of the University of Wisconsin, Madison, were able to reprogram human skin cells into pluripotent stem cells, which have the potential to become any cell type in the body. Yamanaka used the facial skin of a 36-year-old woman and the connective tissue of a 69-year-old man. Thomson’s team used cells from fetal skin and the foreskin of a newborn baby. In both cases, they introduced a slightly different combination of genes into the skin cells to create stem cells that genetically matched the donor without the need for cloning.
Yamanaka’s study was published in the journal Cell on Nov. 20, 2007. Thomson’s appeared at the same time in Science.
Stem cells are unprogrammed cells that have the potential to change into specialized cells, such as those in the heart, lungs or central nervous system. Pluripotent stem cells can function as replacement cells or tissue and thus could have healing powers. A genetic match is important because there is less likelihood the cells will be rejected by a person’s immune system.
Previous research in cloning, which was first used successfully in sheep, helped Thomson and Yamanaka in their discoveries. In cloning, the adult cell’s chromosomes are inserted into an unfertilized egg from which all genetic material has been removed. The egg somehow reprograms the adult cell’s chromosomes, and the reprogrammed genes direct the development of the embryo. The result is an exact genetic match, or clone, of the adult.
Both Thomson and Yamanaka set out to replicate the reprogramming process without using the egg. Thomson compiled a list of 14 genes that have the ability to reprogram human cells. Yamanaka used the same set of genes he had obtained in experiments with a mouse model.
They whittled down the number of genes to four candidates each. Then they used a retrovirus to ferry the genes into human skin cells in a lab culture. For every 10,000 cells treated with this technique, Thomson was able to produce one pluripotent stem cell. Yamanaka’s method produced one in every 5,000 cells. In both cases, the stem cells created were a genetic match with the donor.
Using a retrovirus to insert genes into a cell carries some risks. Many of the new stem cells the scientists created carried multiple copies of the retrovirus, which could result in mutations and cancer. One of the genes used in Yamananka’s suite is a known cancer-causing gene.
Even with these limitations, the studies open the door for an understanding of disease mechanisms, drug screening and toxicology, Yamananka pointed out.
“Once the safety issue is overcome, human iPS (induced pluripotent stem) cells should also be applicable in regenerative medicine,” he said.
The next step would be to uncover a way to create iPS cells without a retrovirus. Additionally, scientists need to find out if these cells differ significantly from embryonic stem cells.
In two related advances, scientists at MIT and the University of Alabama demonstrated for the first time that stem cells created by the method Thomson and Yamanaka used can cure sickle cell anemia in a mouse model. And researchers at the Oregon National Primate Research Center reported another first—the successful cloning of a primate. As a result they were able to obtain embryonic stem cells, which could be useful in studying other diseases that also affect humans.
For more information, see:
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.
These breakthroughs in cloning and regenerative medicine are very exciting. We’ve been regenerating the stem cell system in the bone marrow for decades, using bone marrow transplants, which are really stem cell transplants. But until recently, it wasn’t known that stem cells would actually regenerate other organs.
“It won’t be long before further studies uncover a better method for creating stem cells.”
Research is now moving at a very fast pace. Because of these new discoveries, it won’t be long before further studies uncover a better method for creating stem cells without using retroviruses to insert genes into skin cells. The retrovirus technique is somewhat crude. It carries the risk of disrupting the gene and causing mutation.
With the knowledge gleaned from the Thomson and Yamananka studies, identifying reprogramming genes, someone will figure out a way to bypass gene insertion. The most elegant way would be to devise a small molecule that mimics a certain gene, a surrogate that stimulates the development of a stem cell, making the use of retroviruses unnecessary.
“If pluripotent stem cells are injected into the damaged area, conceivably the tissue could be reconstructed.”
Pluripotent stem cell lines are able to produce muscle, pancreatic beta cells or neurons. You can, in theory, inject them into the proper site of the body, where they then come under control of the tissue and operate in the rejuvenation of that tissue. Suppose a patient has a spinal cord injury due to trauma and lost brain or spinal cord tissue that cannot be replaced naturally. If pluripotent stem cells are injected into the damaged area, conceivably the tissue could be reconstructed. The same is true of other organs like the liver and lungs or in neurological conditions like Parkinson’s disease.
Previous research in mice has shown that the insertion of stem cells can reverse the effect of certain diseases. Now, for the first time, the MIT/Alabama study demonstrates that the induced pluripotent stem cells can cure sickle cell anemia in mice. Several hurdles must be overcome, however, before we find out whether this works in humans.
Human studies would take a long time. Potential toxic effects must be examined. The studies could be fast-tracked because of the possibility of helping so many people; but, certainly, it could be at least five years before the development of clinically safe methods and dosages that don’t cause unexpected side effects or worsen the disease.
The advantage of using skin cells is that they are plentiful and easily accessible, but many of the genes in skin cells are turned off because they’re not needed. We don’t know the long-term ramifications of having genes in the “off” position. It could have effects we can’t predict.
Diabetes would be a logical choice as one of the first diseases to test for stem cell injection in humans. Previous experiments have shown that it can be corrected if the proper cells are injected into the pancreas. Additionally, it’s a disease that affects a large population.
Parkinson’s is a genetic disease that is potentially curable by stem cell injection. A number of blood disorders are also possible targets for this type of treatment, as are some very rare genetic disorders. Rejuvenation of damaged heart tissue after a heart attack and some types of kidney or liver diseases should also be studied.
It would be naïve to say the first disease we’re going to target with stem cells is cancer because it’s a very complex disease that involves multiple pathways. We don’t fully understand most of those pathways. To show that stem cell therapy is efficacious and safe, the best choice would be a relatively simple disease that is surrounded by a lot of knowledge and affects a large population.
Dr. Van Zant is a professor of hematology/oncology in the UK College of Medicine and director of the clinical and research stem cell laboratories in the department of internal medicine. He holds the Lucille P. Markey Chair for Oncology Research.
Each issue of Advances & Insights summarizes an important piece of medical news, accompanied by commentary from a UK expert.
Subscribe here or call 859-257-1000 and provide your mailing address.
1000 S. Limestone
800-333-8874 (toll free)
connected with UK HealthCare. Become a fan of our Facebook and follow us on
Twitter and Youtube to stay up-to-date on community events, programs,
treatments, research, new physicians and more.
© University of Kentucky, Lexington, Kentucky, USA | An Equal Opportunity University