Eli team ‘freezes’ stem cells

Stem cell researchers may find their jobs easier following a Yale team’s discovery of a way to halt stem cell development at the phase that is most useful for genetic therapy.

School of Medicine researchers Zhong Yun, Qun Lin and Yi-Jang Lee discovered that under conditions of hypoxia — low levels of oxygen — stem cells and progenitor cells derived from them are not only able to survive, but are inhibited from developing into mature stem cells. While the research was not focused on the medicinal use of stem cells, the researchers said the discovery will help give scientists more flexibility when conducting their experiments. They originally released their results in an Oct. 18 issue of the Journal of Biological Chemistry.

With the exceptions of adult bone marrow cells and embryonic stem cells, the vast majority of stem cells deteriorate in function as they age, losing the ability to differentiate into a range of cell types as they develop.

Yun, the principal author of the study, said the researchers subjected preadipocytes, or fat precursor cells, to conditions of less than 2 percent oxygen and found that the stem cells remained in a relatively unchanging state instead of differentiating into various cell types.

“Not only do cells not undergo differentiation, but the hypoxia managed to maintain them in that uncommitted state,” Yun said. “It’s just like arrested development.”

Because stem cells have been used to treat patients with leukemia and other genetic diseases, he said the research may prove promising for genetic therapy that involves modification of a patient’s stem cells.

“[Genetic modification] requires long-term maintenance,” he said. “[It] will require special technology to keep them in an undifferentiated stem cell state.”

Scientists were aware, Yun said, that bone marrow cells­ — which maintain their ability to differentiate even in old age ­— existed in low-oxygen environments. But while scientists knew that both phenomena were correlated, they had not established whether low oxygen levels caused development to stop.

Further research may have applications related to diabetes or obesity, but at this time the study’s conclusions are relatively general and unspecific, Lin said.

Like Lin, Yun said he was optimistic about the medical applications of the research but that he was unsure what direction Yale’s team will take in further studies. He said possible areas of future research may include intracellular pathways and the molecules involved in the process, and whether or not bone marrow cells react in exactly the same way as the progenitor cells involved in the study.

“There’s a lot of things we don’t know but we’re trying to understand,” Yun said. “We’re going to build upon this and use this knowledge to address bigger questions.”

Some students said they felt that the research can contribute significantly to simplifying stem cell research.

“If this can really maintain the undifferentiated state of stem cells, it would facilitate stem cell research to the next level,” biology major Carol Duh ’07 said. “It could also address the shortage of stem cell resources — which can circumvent a lot of ethical issues involved in stem cell research.”

The government currently only provides funding for research using existing stem cell lines, which has put financial strain on institutions that cannot experiment without federal subsidies.

This is the second paper that the team, which has been studying stem cells for about five years, has published on the subject. Their first paper, published in 2002, also centered on the inhibition of stem cell differentiation under hypoxic conditions.

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