Researchers around the world are collaborating in order to understand a fundamental building block within the human body.

These building blocks are stem cells, which exist within animals and are responsible for the growth and maintenance of their organs. They have been a topic of significant interest and controversy since their discovery, and recent developments within the field — such as induced pluripotent stem cells — have thrust the cells back into the scientific limelight.

Functions and Possibilities: What Are They Again?

Stem cells are pluripotent, which means they are able to differentiate into any cell type in the body. They are the precursors to differentiated cells — such as those in the liver or kidneys — and have regenerative properties that are of great interest to scientists.

Kenneth Kosik, co-director of the Neuroscience Research Institute at UCSB, said researchers are looking into stem cells to develop regenerative therapies for patients who have lost cells to disease or age.

“In general people are looking to stem cells as a possible [method of] repair for cells in the body that die, whether [they are] cells that die from diabetes or Parkinson’s disease.” Kosik said. “There’s much of that going on already.”

In 2004, California voters passed Proposition 71 in order to create the California Institute for Regenerative Medicine. CIRM was established to provide grants to stem cell researchers, and UCSB has received funding for a series of studies — as well as the renovation of the laboratories in Biological Sciences II building, where the Center for Stem Cell Biology and Engineering is located.

Each human stem cell project in Santa Barbara must be approved by a stem cell research oversight committee, as required by law. Michael Osborne, research professor of history of science and environmental studies, said ethics training is mandatory for stem cell scientists.

“Training in bioethics is a required part of the activities of the students and post-doctoral researchers who win a place in the laboratories of Professors Clegg and Soh,” Osborne said.

UCSB and Regenerative Medicine

Kosik said the CSCBE is trying to understand the basic mechanisms of how stem cells function.

“They’re incredibly fascinating cells because they have this dual identity.” Kosik said. “The stem cell can divide to create two daughter cells: One cell which retains the original identity as a stem cell, and another that can become any cell in the body.”

Last May, Kosik and postdoctoral fellow Na Xu published a paper in the journal Cell that detailed a control protein that scientists could use to return differentiated cells to their pluripotent state, allowing scientists to possibly generate stem cells for patients using their own cells.

UCSB is also home to the Center for the Study of Macular Degeneration, which recently received a $2.5 million grant from CIRM to study the use of stem cells for treatment of the disease.

Kosik said the UCSB researchers are also looking into the similarities between cancer and stem cells as well as the possible effect stem cells may have on the aging process.

“We’re very interested in trying to learn about the difference between a stem cell and a cancer cell, because some stem cells can become cancerous, and we’re also trying to learn whether or not stem cells have some control over the aging process.”

The Induced: Bringing Pluripotency Back

A controversial issue with stem cells began in the early stages of the research because embryonic stem cells would be best for research. According to Dennis Clegg, co-director of the CSCBE, induced pluripotent stem cells, or iPS, can circumvent many problems with the use of stem cells by turning some of the patient’s cells and con¬verting them back into their adaptable state.

“A big breakthrough that is one of the most exciting in stem cell research is induced pluripotent stem cells,” Clegg said. “IPS are made using four genes to reprogram any differentiated cell in a patient’s body into a stem cell. The first were made from lung fibroblasts… now reports show that you can make them from a variety of types of cells that you can reprogram.”

According to Clegg, Shinya Yamanaka, a stem cell researcher in Japan, discovered how to revert the cells back to a pluripotent state in mice. The next year, Yamanaka and Jamie Thomson — the first scientist to isolate stem cells and an adjunct professor at UCSB — independently did the same in humans.

IPS could end much of the controversy surrounding stem cell research as well as some health benefits in patients because it is made from the patient’s own cells, not from human embryos.

Sherry Hikita, director of the Laboratory for Stem Cell Biology and Engineering at UCSB, said the benefits of using iPS cells go beyond ethical concerns.

“The advantage of using an iPS cell for regenerative therapy is that there is no immune rejection. If I take your skin cell, and I reprogram it with the four genes … then I inject it back into you then your body would recognize it as itself.”

Clegg said the macular degeneration researchers are currently trying to use iPS cells to make ocular cells.

Out of the Test Tube, Into the Clinic… But Not So Fast

On Jan. 23 of this year, the first stem cell-derived treatment was approved by the Food and Drug Administration for clinical trials. Geron Corp., the company that developed the treatment, has used stem cells to repair spinal injuries in mice. The stem cells would repair the myelin sheath around the cells in the central nervous system, allowing the mice to walk again.

Researchers at UCSB joined with other scientists and doctors at USC, Caltech, City of Hope and University College in London with the goal of creating an Investigational New Drug — the first step of application to the FDA — in four years.

However, the road to FDA approval for clinical trials is long, and many prerequisites have to be met before the drug can be acceptable.

“There are certain standards that you have to adhere to if you want to apply for a clinical trial to the FDA.” Hikita said.
Many stem cells are grown with reagents that have animal products, such as mouse embryonic fibroblast. Secretions from the mouse embryonic fibroblast support the stem cell and help it grow. However, this can create complications in humans.

“But what can happen over time is that some of the mouse proteins will incorporate or bind to the surface of the humans cells,” Hikita said.

If the cells are injected into a patient, the patient’s immune system will not recognize them as its own and will reject the cells, according to Hikita.

Also, stem cell cultures require a large amount of care, according to Hikita. Although stem cells are grown in a matter of weeks, if they are exposed to the smallest amount of contamination, the cells are ruined. Then the scientists must start making the cells again, wasting weeks of work. Hikita said UCSB researchers are observing Geron’s methods in order to improve the culturing process.

“We wanted to learn from them what some of their protocols are, not specifically related to their spinal cord project, just basic culturing cells,” Hikita said. “There’s a lot of difference between growing stem cells for basic research purposes compared with growing stem cell derivatives that you intend to use as a treatment in patients.”

Looking Onward

Stem cells have been proposed as a treatment for many diseases, ranging from muscular dystrophy to type I diabetes. While treatments are not fully developed, the future looks bright for stem cell research.

Clegg said the lifted ban on federal stem cell research funding has opened new doors for scientists and physicians.

“When President Barack Obama lifted President Bush’s ban [on stem cell research], he made the point that there’s a moral obligation to cure the sick. If we make cells that can treat the diseases then morally we should do it,” Clegg said. “We have a moral obligation to do so.”

According to Kosik, there is still a good amount of research to be done.

“We face the mystery of nature. Nature does not reveal its secrets very easily,” Kosik said. “You have to be very clever and have a lot of research funds to figure out what looks very easy, but is very complicated.”