Confining Cells within Geometric Structures Key to Replicating Embryonic Development

It’s like trying to capture, and then recreate, a moment in time: the exact instant after fertilization when a small group of dividing cells begin to organize themselves into the various cellular layers that will one day make up the skin, the heart, the liver and the brain. But for all the advances in our understanding of how an embryonic stem cell grows, matures and differentiates—scientists still can’t replicate that very important process in the lab.

Forty-two hours after they began to differentiate, embryonic cells are clearly segregating into the various layers that will one day become specific tissues and organs. Researchers say the key to achieving this patterning in culture is confining the colonies geometrically. [Credit: The Rockefeller University]

Forty-two hours after they began to differentiate, embryonic cells are clearly segregating into the various layers that will one day become specific tissues and organs. Researchers say the key to achieving this patterning in culture is confining the colonies geometrically. [Credit: The Rockefeller University]

But now, scientists at The Rockefeller University have tried something new, and in so doing have finally found a way to stimulate this organization, thus mimicking in a petri dish what happens in the human embryo. The missing ingredient, the researchers found, wasn’t a molecule or chemical compound. Rather, the team just had to use a bit of geometry.

Reporting in the June 29 issue of the journal Nature Methods, the Rockefeller team—led by Dr. Ali Brivanlou—describes how they constructed microscopic circular patterns on glass plates that confined embryonic stem cells inside, similar to a hedge maze.

To their amazement, the cells confined within these patterns soon began to go through gastrulation, the process by which embryonic stem cells begin to form highly organized layers that eventually mature into the body’s various organs and tissues. A second group of cells not confined within these patterns, however, did not.

The next question they had to figure out, according to the researchers, was why.

To solve this mystery, Brivanlou and his team next monitored specific chemical signals between the cells as they matured. In so doing they uncovered a delicate arrangement of chemical cues—molecular ‘on-and-off-switches’—that guided each cell down one developmental path as opposed to another. What were crucial to these cues going off without a hitch, the researchers found, were the geometric patterns.

As Dr. Aryeh Warmflash, one of the paper’s lead authors, stated in this week’s news release:

“At the fundamental level, what we have developed is a new model to explore how human embryonic stem cells first differentiate into separate populations with a very reproducible spatial order just as in an embryo. We can now follow individual cells in real time in order to find out what makes them specialize, and we can begin to ask questions about the underlying genetics of the process.”

Added Brivanlou:

“Understanding what happens in this moment, when individual members of this mass of embryonic stem cells begin to specialize for the very first time and organize themselves into layers, will be key to harnessing the promise of regenerative medicine.”

The Art of Public Service

Usually we use this space to talk about important or interesting developments in stem cell research. Developments that help increase our understanding of how stem cells work and how we can use them to develop much-needed treatments for a wide variety of diseases and disorders. But every once in a while it’s good to stand back and take a moment to appreciate the people who work hard to make all of this possible. I don’t just mean the researchers and the scientists; I’m also talking about our tireless staff. And in this case, I’m talking about one in particular, Art Torres.

Our Board Vice Chair and tireless patient advocate, Art Torres

Our Board Vice Chair and tireless patient advocate, Art Torres

Art is having a truly remarkable career, one that shows no sign of slowing down. He started out as a community organizer, worked with the legendary Cesar Chavez and then went on to serve 20 years in the state legislature (8 in the Assembly, 12 in the Senate) before becoming the Chairman of the California Democratic Party.

He joined the stem cell agency in 2009 as both a patient advocate (he’s a colon cancer survivor) and as the Vice-Chair of our governing Board, the Independent Citizens Oversight Committee.

In 2010 he was sworn in by then Mayor Gavin Newsom to a four-year term on San Francisco’s Public Utilities Commission.

And as if all that isn’t enough, he has now agreed to be a Trustee for the University of California Santa Cruz Foundation Board. He was elected, unanimously, by the other Board members to serve in a leadership role to help support what the Foundation’s website calls “the university’s vision of academic excellence and its commitment to public service.”

It’s not too surprising really that Art would take on this latest challenge. UC Santa Cruz is his alma mater and he rarely wastes an opportunity to cheer on the “Slugs” as they are affectionately known.

So it’s appropriate that as we celebrate the 4th of July we celebrate and honor Art for his devotion to public service. Long may it continue.

kevin mccormack