Caught between a ROCK

Courtesy of Xiangyunli

The paper:

K. Watanabe et al., "A ROCK inhibitor permits survival of dissociated human embryonic stem cells," Nat Biotech, 25:681–86, 2007. (Cited in 59 papers)

The finding:

To address the problem of human embryonic stem (ES) cells undergoing programmed cell death when dissociated into single cells, a team led by Yoshiki Sasai of the RIKEN Kobe Institute in Japan performed a comprehensive chemical screen for inhibitors of apoptosis. The researchers discovered that a Rho kinase (ROCK) inhibitor called Y-27632 significantly enhanced the survival rate of single ES cells in culture and in suspension.

The impact:

The study provides "a major technical advance," says Michael Olson, of the Beatson Institute for Cancer Research in Glasgow. "It enables people to more easily grow human [embryonic] stem cells, which are inherently fragile and difficult to culture."

The mechanism:

Derrick Rancourt and Roman Krawetz at the University of Calgary showed that ROCK interacts with adhesion molecules called cadherins (BioEssays 31:336–43, 2009). Rancourt says that the ROCK inhibitor changes communication patterns by desensitizing ES cells to their external environment, which gives them extra time to make important cell-cell interactions.

The sell out:

Soon after the Hot Paper came out, commercial supplies of Y-27632—which RIKEN patented—sold out and were unavailable for the next few months. "This well describes how people needed something like this," says Sasai. Rancourt and Krawetz are working on alternative formulations that don't involve ROCK inhibitors, but they're "not yet optimal" for cell survival, says Krawetz.