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U of M researchers improve method to create induced pluripotent stem cells
Date:7/20/2011

University of Minnesota Medical School researchers have developed a new strategy to improve the development of induced pluripotent stem cells (iPS).

Currently, iPS cells are created by introducing four defined genes to an adult cell. The genes reprogram the adult cell into a stem cell, which can differentiate into many different types of the cells in the body. Typically, the four genes introduced are Oct4, Sox2, Klf4 and c-Myc, a combination known as OSKM.

The U of M researchers found that by fusing two proteins a master stem cell regulator (Oct4) and a fragment of a muscle cell inducer (MyoD) they succeeded in "powering up" the stem cell regulator, which can dramatically improve the efficiency and purity of reprogrammed iPS cells.

"Our team discovered that by fusing a fragment of the powerful protein MyoD to Oct4 we could create a 'super gene' which would improve the iPS reprogramming process," said senior author Dr. Nobuaki Kikyo, Stem Cell Institute researcher and University of Minnesota Medical School associate professor. "The result is what we termed M3O, or 'super Oct4' a gene that improves the creation of iPS cells in a number of ways. In the process we shed new light on the mechanism of making iPS cells."

The challenge with the previous method OSKM has been that very few cells actually become iPS cells during reprogramming. In fact, the rates currently stand at about 0.1 percent. Another issue has been tumor development. Because some of the reprogramming genes introduced are oncogenes, the risk of developing tumors grows.

The research, led by Kikyo and Dr. Hiroyuki Hirai, both from University of Minnesota Medical School and Stem Cell Institute, led to a new gene model that minimizes such complications while amplifying the benefits of the process.

According to Kikyo, the new gene model called M3O-SKM improves iPS development by:

Increasing efficiency. The efficiency of making mouse
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Contact: Justin Paquette
jpaquett@umn.edu
612-626-7037
University of Minnesota
Source:Eurekalert

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