Reprogrammed Stem Cells Take Research To Greener Pastures

By reprogramming somatic cells, researchers at the Johns Hopkins research institute have achieved new feats in the field of studying sickle cell anemia, taking research in the field to a different level altogether.

According to the team, the method establishes a human cell based system, by reprogramming these cells to a state similar to those of embryonic stem cells, making the process of research much faster and efficient.

"We hope our new cell lines can open the doors for researchers who study diseases like sickle cell anemia that are limited by the lack of good experimental models," says Linzhao Cheng, Ph.D., an associate professor of gynecology and obstetrics, medicine and oncology and a member of the Johns Hopkins Institute for Cell Engineering.

Initially the team had tried to improve upon the already established methods of reprogramming adult cells into induced Pluripotent Stem (iPS) cells. The iPS cells look and behave the same way as the embryonic stem cells.

However, as testing continued on various genesdefine, improved reprogramming emerged, mainly after the addition of a viral protein known as SV40 large T antigen.

The change in efficiency of reprogramming after the introduction of the new viral protein was tested in both the fetal as well as adult human skin cells. Without the protein, cells form embryonic stem cell-like clusters in three to four weeks. Whereas, with the protein, the cells started looking like embryonic stem cells in just 12 to 14 days.

"Not only did T speed up reprogramming, we also found that it increases the total number of reprogrammed cells, which is great because often in reprogramming, not all cells go all the way," says Cheng.

He however necessitated rigorous follow-ups to determine whether the reprogrammed cells actually behaved like pluripotent embryonic stem cells.

"Many of them look right but they're probably just half cooked-like a boiled egg, you just can't tell the difference by looking at the outside," he said.

Once this efficient method of reprogramming was established, the researchers reprogrammed human cells that contain the mutation associated with sickle cell anemia.

It was found that, embryonic stem cell-like clusters were visible 14 days after they initiated reprogramming and from these clusters the researchers established three different cell lines that both look and behave like human embryonic stem cells.

"One challenge to studying blood diseases like sickle cell anemia is that blood stem cells can't be kept alive for very long in the lab, so researchers need to keep returning to patients for more cells to study," says Cheng. "Having these new cell lines available might enable some bigger projects, like screening for potential drugs."