The future of stem cells, Texas and politics

The Friday, January 26, 2007 Austin American Statesman editorial, “Stem cell opposition could steer research away from Texas,” flatly states that Governor Rick Perry’s $3 Billion dollar cancer research initiative won't help at all if it doesn't include funding for embryonic stem cell research. The Statesman editors doubt that there will be any scientists to spend the money on.

The editorial is ridiculous – and, as the editors admit, political - in light of daily strides in ethical stem cell research and Texas’ strong research community.

Texas hospitals were among the first in the nation to offer umbilical cord blood transplants. Cooperation between Texas universities, medical schools, NASA and foreign researchers led to technology which allowed the development of embryonic-like stem cells and liver cells from umbilical cord stem cells.

Texas is already enough of a leader in ethical stem cell research to lure the President of the International Society of Stem Cell Researchers, Paul Simmons, Ph.D., away from Australia to the University of Texas Health Sciences Center at Houston.

We also have Diego Castrillon, MD, PhD., who moved from Massachusetts to the University of Texas Southwest Medical Center. Dr. Castrillon is credited with research into the "Fox O's." These are "transcription factors," or local proteins that cause the expression of certain genes. They promote the health of adult stem cells and suppress cancer cells.

This month’s issue of the journal, Cell, will include a report on further research on FoxO’s. From a press release at "Newswise"

The FoxO1, O3, and O4 transcription factors regulate genes in the complicated cell signaling network known as PI3K-AKT, or simply PI3K. Scientists have discovered that PI3K signaling is intimately involved in fundamental cell processes such as metabolism, aging, and protecting the body against cancer. The PI3K circuit has been found to be disrupted in many forms of cancer, making it a hot topic in cancer research labs and drug company boardrooms.

Based on previous work in his laboratory, DePinho, working with Diego Castrillon, MD, PhD, (who is now at the University of Texas Southwest Medical Center), determined that the three FoxOs had redundant, overlapping functions: To uncover those functions, it would be necessary to engineer mice that lacked all three FoxO transcription factors.

To make the task even more difficult, mice lacking FoxO1 die in the womb. DePinho and Castrillon had to engineer mice whose FoxO genes would function normally during development, but would contain a mechanism allowing them to be switched off in adulthood at the scientists’ will. It took DePinho’s team about two years to get the system to work, which Gilliland hailed as a “true tour-de-force of mouse genetics.”

Mutant FoxOs have been implicated in leukemia, and for Gilliland, who studies blood cancers, the triple-knockout mice were an opportunity to dig deeper into the issue. Unexpectedly, however, deletion of FoxO1, 03, and 04 caused blood cell abnormalities but not outright leukemia. A bigger surprise was that the blood stem cells “were really in trouble without those transcription factors,” he said, dividing too rapidly, losing their ability to renew themselves, and dying out. “This means that FoxOs contribute to the longevity of stem cells, and if you take them away, you dramatically shorten stem cells’ lives.”

Looking further, Gilliland and his colleagues found that the damage was being caused by reactive oxygen species, or ROS, a toxic byproduct of cells’ energy production. When the mice were treated with anti-oxidants, the stem cells regained health and longevity. “So, the FoxOs are acting as natural antioxidants,” said Gilliland. Conceivably, he added, drugs could be developed to manipulate the FoxO pathway and extend the lives of stem cells beyond their natural limits, which could aid their use in repairing diseased body tissues.

Texas' limited research funds should be spent on supporting the State's cord blood bank system and continuing research that will give us real cures for Texas' patients.

Note: First paragraph edited for grammar at 10:25 AM CST.