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Stem Cells 2.0: Beyond the Hype, Engineers Look to Build Fast

By Alex Hutchinson, Popular Mechanics, November 27, 2007

Engineers who figure out how to take the delicate results of lab experiments and make them robust enough to survive the onslaught of industry, have a long road to follow in order to get from breakthrough to application. Thus, the news last week that adult skin cells had been reprogrammed using a novel technique, to transform them into embryonic stem cells, was seen as only the beginning and not the end by biomedical engineer PeterZandstra and others like him.

“It’s a huge step,” Zandstra says. “But the stem cells themselves are not useful for anything. That was the problem before this announcement—and that’s still the problem today.”

"Any lab with standard molecular biology can do reprogramming without difficulty”, said James Thompson, whose team authored one of the bold new studies. Even though the ultimate focus is still on recombining cells in order to cure illness and disease such as Parkinson's, Heart Disease, and Autism, the international focus is now on efficiency. While tailoring them to a specific purpose, and using a process that is repeatable and straight forward, researchers need to be able to produce the new stem cells in large quantities with high purity. The development of "bioreactors" to fulfill precisely those requirements is already underway by many groups around the world. One such group is Zandstra and his team at the University of Toronto’s Stem Cell Bioengineering Lab.

“I feel kind of funny saying this to Popular Mechanics, but this is not rocket science,” Zandstra says. “It’s an engineering challenge: How do you take a phenomenon that’s clearly robust enough that it can be reproduced, but isn’t yet something that is routine, and move it in that direction?”

The process of laying out the groundwork has already been initiated by stem-cell engineers, although, they are still under-the-radar.

To grow adult stem cells with the goal of enabling bone grafts, Teng Ma, an engineer at Florida State University, developed a “perfusion bioreactor”. Earlier this year, the Department of Defense awarded him an $824,000 grant spanning four years to further develop his patented device.

Resulting in a dramatically increased stem cell yield of billions of cells per milliliter, a bioreactor was created that used polymer threads as a scaffolding to help stem cells grow. The accomplishment was achieved by Ohio State University researcherShang-Tian Yang.

The yield of stem cells from umbilical cord blood as also dramatically increased in 2005 by a method developed by Zandstra's group.

Engineers will be seeking to develop new bioreactors, new environments that facilitate rapid cell production, that put all the new cells into action. But taking skin cells and applying them to treatment probably isn't the best first step, even though the simple act of adding four genes to human skin cells was a straightforward breakthrough and opened the door of stem cell research wide.

“It’s not clear how efficient the process is,” Zandstra says, “and it’s not clear what the mechanisms underlying the process actually are.”

The method needs to be proven safe and free of mutations before any other step. But the most immediate goal will remain unaffected by this temporary concern: using stem cells to create “diseases in a dish” to learn more about how genetic diseases develop. Later, once the issue is resolved, tissue engineering can commence for application in human transplants.

"Further studies are essential," said the Japanese research team. In order to accelerate stem cell production, three approaches must be considered.

In Silico
This refers to computer testing by researchers prior to taking their work into the laboratory. Zandstra created detailed computer models of how stem cells grow and then differentiate into their final adult form. He said that, "if you describe something mathematically, you have a much better understanding of it than if you just observe it."

In Vitro
This refers to evaluating the cells while in a test tube or Petri dish. Zandstra says that the practical impact of the cells is first noticed in this stage. New ways of treating or controlling a disease can be developed. He added that, “if someone has sickle-cell anemia, or any disease that’s due to a mutation, and you take a cell from that patient, then you can generate a stem cell that also carries that same mutant gene."

In Vivo
Humans testing will not be the first step, but in vivo translates to "in living creatures". The immune systems of living mice were regenerated by injecting their bone marrow with stem cells last week. Researchers at Stanford University were able to accomplish this but their announcement was missed by most due to the excitement surrounding last weeks announcements.

So the next big question remains: When we can expect the next major milestone? The word "years" has been used by Johns Hopkins and the White House. But Stem Cells 2.0 may be in effect before we even realize it; a sentiment thatZandstra agrees with.

“These things happen so quickly,” he says. “Who would have thought that we could even do what we can do now, a few years ago?”


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