Stem cell research expands at UC Irvine

By CATHY TRAN

The Orange County Register

A major expansion is beginning at UC Irvine in the study of human embryonic stem cells, which have the potential to become any of the more than 200 cells in the body and offer hope of a repair kit for people suffering from injuries and disease.

The California Institute for Regenerative Medicine, which operates the state's publicly funded stem cell program, has awarded six UCI scientists $3.5 million to examine such things as whether certain drugs slow the growth of the cells or how mutations may cause such cells to go bad.

The institute was created in 2004 after voters passed Proposition 71 to fund human embryonic stem cell research through the sale of $3 billion in bonds. Litigation froze distribution of the funds for more than two years but a $150 million state loan launched this first wave of funding.

The $3.5 million is part of the $45 million that the institute gave in its first grants to investigators at 20 institutions to expand a field that is comparatively new and, so far, is not close to providing verifiable medical benefits.

"The value of these grants is tremendous," said Hans Keirstead, co-director of the UCI Sue and Bill Gross Stem Cell Research Center. "I'm most excited by the fact that the projects span basic discovery through applications to disease. We're in a very unique position for getting from bench to bedside."

The California Court of Appeal in San Francisco ruled last week that the proposition "suffers from no constitutional or other legal infirmity," a decision that is expected to free up more money. "It really ensures us that we're on the right track," Keirstead said. The university is now raising money to establish a new stem cell research center.

---

INVESTIGATING MULTIPLE SCLEROSIS

Thomas Lane, professor of molecular biology and biochemistry, $425,594

Lane is studying how embryonic stem cells may help repair nervous system damage in patients with multiple sclerosis. He is starting with mice that have a mild paralysis in their hind legs, causing them to wobble. The impaired motor skills are caused by loss of a coating, called the myelin sheath, around neurons. "It's like an electric wire with the rubber coating stripped," Lane said. Not having a myelin sheath disrupts communication among cells in the brain. With the grant, he hopes to start answering questions such as: How long do the stem cells survive and function? How can we direct the cells to migrate to the damaged neurons?

KEEPING STEM CELLS HEALTHY

Vincent Procaccio, assistant professor of pediatrics, $623,500

Embryonic stem cells may lose the capacity to generate desired cell types for therapy over time. Procaccio is testing whether this may be caused by damage to the mitochondria, commonly referred to as "the power plants of cells." Mitochondria are responsible for burning the calories in food with oxygen to generate carbon dioxide, water, and energy for cells. Some by-products of this process are reactive forms of oxygen that cause mutations in the mitochondrial DNA, disrupting its ability to produce energy and causing cell death. It's like "the smoke generated by coal-burning power plants," he said. Procaccio will monitor mitochondrial DNA mutations in embryonic stem cells to see how they affect the cells' ability to change into neurons and what treatments can slow their mutation rate.

COOPERATING WITH THE IMMUNE SYSTEM

Brian Cummings, assistant professor of physical medicine and rehabilitation, $619,223

Patients who will undergo future stem cell therapies will likely need drugs that suppress their immune system so that the foreign cells are not rejected. These drugs, however, have been shown to affect the fate of stem cells. Studying spinal cord therapy, Cummings found that "adult" stem cells successfully divided into two types of brain cells in mice that did not have an immune system. But when normal rats were given immunosuppressant drugs, only half of the stem cells survived. Cummings will test how the drugs and the immune system interact with embryonic stem cells and which immunosuppressive drugs may work best, by exposing the cells to different drugs before transplanting them into mice with spinal cord injuries. He'll look at how fast the cells divide, how long they divide, and what cells they eventually become. "Studying a basic mechanism like this could serendipitously affect other therapies, such as for heart disease or diabetes," he said.

GENERATING HUMAN EGGS

Grant MacGregor, associate professor of developmental and cell biology, $623,781

A shortage of human eggs is limiting progress in embryonic stem cell research and therapeutic cloning. Alternatively, animal eggs, such as those from rabbits, can be combined with human DNA and mitochondria, but the resulting cells can have problems producing optimal energy for cell growth. MacGregor is investigating how to produce female reproductive cells from human embryonic stem cells to generate a limitless supply of eggs. To do this, he plans to put embryonic stem cells into a substance that mimics the conditions inside a normally developing embryo by altering hormones and growth factors to coax the stem cells to develop into eggs. After removing the egg's nucleus, the nucleus from a patient's cell can be transferred into it.The eggs would then be stimulated to develop into embryonic stem cells that are compatible with the patient's immune system. This, MacGregor said, could make donation of eggs unnecessary. "It would be tragic if women were encouraged to donate (eggs) for stem cell research only to find out 30 to 40 years from now that there are significant health problems associated with that."

REPAIRING IRRADIATED TISSUES

Charles Limoli, associate professor of radiation oncology, $625,617

Limoli is studying how to improve the repair and recovery of normal tissues damaged during the course of radiotherapy. Irradiation of the brain to treat cancer can lead to certain types of cognitive impairment thought to be caused by the loss of neural stem cells. Limoli hopes to replace neural and other stem cells lost during radiotherapy through the use of implanted human embryonic stem cells. Radiation poses a challenge since it may change the course of development for a stem cell. "When you implant stem cells, the surrounding tissues impact what these cells will turn into," Limoli said. The fate of the same stem cell may be different depending on whether it's implanted in a normal tissue or an irradiated tissue. Limoli also plans to study the tumor risks of implanted human embryonic stem cells, and how to direct these cells to develop into the desired cell type.

UNCOVERING THE MYSTERIES OF WEAK MUSCLES

Kyoko Yokomori, associate professor of biological chemistry, $623,500

Yokomori is studying a form of muscular dystrophy that initially weakens the facial, shoulder and upper arm muscles, and sometimes spreads down to the legs. "The muscles sort of disappear," she said. "There's no effective treatment and the mechanism of how this disease happens is not very wellunderstood." But there's one clue that she's digging into: People with the condition have a shortened repeating unit at DNA sequences linked to disorder. Yokomori is using embryonic stem cells to study how the shortened repeats affect pathways that may lead to weakening of the muscles. "In order to understand this development disorder, we need to study it at the earliest possible stage," Yokomori said. "It's inheritable, so obviously there's some kind of abnormalities there at the beginning."

Contact the writer: 714-796-6009 or ctran@ocregister.com

Listen to stories like this and more: Audio news & Podcasts

http://www.ocregister.com/ocregister/healthscience/abox/article_1598288.php