Scaling up stem cells: Project aims to churn out cells in quantity, quality
March 28, 2007
For scientists, one of the charms of human embryonic stem cells is their ability to divide and replicate — as far as we know — forever in the culture dish. That defining trait, the ability to constantly make new cells, suggests it might be possible to generate a limitless supply for therapy, research and industrial applications such as high-throughput drug screens.
But human embryonic stem cells are far from tame. In fact, they are notoriously fickle in culture, always wanting to differentiate into something, and they require constant attention if the cell lines are to be maintained in their pure, undifferentiated state. What’s more, once scientists have directed the all-purpose stem cells down a specified developmental pathway to becoming, say, heart cells, for example, making enough of those cells to be used in clinical settings is a challenge so far unmet by biomedical science.
Now, however, with the help of a Wisconsin Institutes for Discovery (WID) seed grant, a team of noted UW–Madison stem cell researchers is taking the human embryonic stem cell down the path to mass production.
“If we are successful with an initial clinical trial with a few patients, it then becomes necessary to scale up for hundreds or thousands of patients,” explains Derek Hei, principal investigator for the WID seed project and director of the Waisman Clinical Biomanufacturing Facility. “The biggest challenge is consistency in the quality of the product.”
Working with cardiologist Timothy Kamp and chemical and biological engineer Sean Palecek, Hei is spearheading the effort to develop techniques for mass-producing human embryonic stem cells suitable for use in practical applications such as drug screening and human clinical trials.
“It’s a platform technology,” says Hei. “For us, it’s getting our foot in the door to move stem cells toward the clinic.”
For Hei and his group, the challenge is not just making stem cells by the truckload, but knowing the cells — each of which are composed of thousands of different proteins and genes — well enough to ensure they are both safe and effective.
“We have to understand the cells, characterize them and test them so we know that they’ll do what they are supposed to do.”
Hei’s group proposes developing a closed, computer-operated system to precisely control colony size, shape and spacing, which are key to keeping stem cells happy, healthy and undifferentiated. The team will also utilize engineered cells to inhibit differentiation and maintain pure colonies of the all-purpose stem cell. Different types of engineered cells will be used to drive differentiation in a particular direction, toward heart cells in the case of the group’s WID seed project.
“There are layers of complexity that normally aren’t there in manufacturing,” says Hei of the new WID project. “We need to determine what controls we can put in place to get a better handle on controlling the cells.”