A Bed Of Mouse Cells Helps Human Cells Thrive In The Lab

Jan 7, 2015
Originally published on January 7, 2015 12:35 pm

A drug that is used worldwide to treat malaria is now being tested as a treatment for cervical cancer. This surprising idea is the result of a new laboratory technique that could have far-reaching uses.

Our story starts with Dr. Richard Schlegel at Georgetown University Medical Center. He's best known for inventing the Gardasil vaccine to protect women from cervical cancer.

Schlegel wished he could take cancer cells from women who came to the hospital for treatment and grow them in the lab to learn more about this disease.

"People have tried growing cells in culture before, but they've been very crude experiments, essentially," he says. Most of these freshly collected cells die off quickly in the lab.

But Schlegel had an idea for a radically new method to grow all sorts of human cells. The secret to keeping them alive indefinitely is to grow them on a bed of cells that come from mice. These mouse cells have been blasted with radiation to prevent them from multiplying, and the culture is then treated with a compound (called a ROCK inhibitor) that regulates cell growth.

You can see these spindly cells coating the bottom of a flask when you look at them through a microscope.

Schlegel says he doesn't know exactly what these mouse cells provide the human cells to keep them alive and growing. "There are probably several growth factors that they secrete that are important ... and we have experiments ongoing to identify what those factors are," he says.

If he can figure that out, eventually he can dispense with the mouse cells. But for now, the layer of mouse cells is the key.

So far, he has grown more than 30 types of cancer cells — as well as many normal human cells that he studies for comparison. All told, Schlegel says, he has grown up cells from 700 different samples of human tissue.

Recently he took some cervical cancer cells and started dosing them with drugs to see what would kill them. He tried all sorts of other available medicines, not not just drugs used to treat cancer.

And much to his surprise, he found that a drug commonly used to treat malaria will also kill cervical cancer cells. It's a form of artemisinin.

Schlegel is now collaborating with researchers at the Johns Hopkins University School of Medicine to test this drug in women who have precancerous growths on their cervix.

Dr. Connie Trimble is running the drug trial at Johns Hopkins. She will offer this drug to women who are likely to require cervical surgery in the coming months. She hopes that, instead, the drug will kill off the cervical cancer cells in women, as it did in the lab.

"If it works, this is a game-changer," Trimble says, "because it puts control of treatment in the hands of the woman. In low-resource settings, or settings where women don't have access to health care, they can do it themselves."

Doctors already know this anti-malarial drug is safe, so it could be a front-line treatment in parts of the world where surgery simply isn't available. It would require an easy diagnostic test women can use at home; Trimble says that's also in the works.

And cervical cancer is just the start. Dr. David Rimm at the Yale University School of Medicine learned about the Georgetown cell-growing method when it was first published two years ago. And now he's using it to generate cell lines.

"It's pretty cool," he says. "We have over 100 [types of cells growing] in our facility."

Rimm says this is a huge step for research labs. It used to be that he could only study a few perpetually growing cell lines, and those were biologically pretty messed up.

"We can now have 40 or 50 cell lines from 40 or 50 different tumors from a population, and they all grow," he says. "And we can now do cell-line type studies, but on populations of cell lines as opposed to two or three."

That gives him the same advantages scientists get when they test new drugs on dozens of people instead of just a few.

Schlegel says at least 30 labs around the world are now using this technique, which is called "conditional reprogramming" of cells. And at the moment, everyone is hopeful that it will be the next big thing for studying diseases in the lab. But it's still just a bit early to make that bold of a claim.

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STEVE INSKEEP, HOST:

Researchers are asking if a drug designed for one purpose might be used for another. The drug is used worldwide to treat malaria. The researchers want to know if it works as a treatment for cervical cancer. A new lab technique may help them find out, as NPR's Richard Harris reports.

RICHARD HARRIS, BYLINE: The story starts with Richard Schlegel, the doctor who invented the Gardasil vaccine to protect women from cervical cancer. Schlegel wished he could take cancer cells from every woman who came into the hospital and grow them in the lab to learn more about this disease.

RICHARD SCHLEGEL: People have tried growing the cells in culture before. But they've been very crude experiments, essentially.

HARRIS: Most of the time, these cells die off pretty quickly. But Schlegel had an idea for a radically new method to grow all sorts of human cells in his lab at Georgetown University. And these days, it's a finely honed system starting in the operating room and then going through the pathology department and up to his lab.

SCHLEGEL: The tissue comes in here, and it's processed over here on two different tissue culture hoods.

HARRIS: These carefully ventilated workspaces reduce the risk of contamination. The cells are gently moved into a flask where they can grow indefinitely. The trick is that these flasks have a layer of mouse cells that feed the human tissue.

SCHLEGEL: Yeah, you can see some of these spindly cells over here.

HARRIS: And so what exactly are the mouse cells providing?

SCHLEGEL: We don't know. There are probably several growth factors that they secrete that are important for the growth of these. And we have experiments ongoing to identify what those factors are.

HARRIS: If he can figure that out, eventually he can dispense with the mouse cells. But for now, the layer of mouse cells is key.

SCHLEGEL: So if you have the cells growing like this they'll grow forever.

HARRIS: And how many different kinds of cancer cells have you been able to grow up in this manner?

SCHLEGEL: We've probably got about 30 different types.

HARRIS: All told, Schlegel says he has grown up cells from 700 different samples of human tissue - some healthy, some diseased, all available for study. Recently, he took some cervical cancer cells and started dosing them with drugs to see what would kill them.

SCHLEGEL: And not just anticancer drugs. For example, we discovered and what we're working on right now is an antimalarial that kills cervical cancer cells.

HARRIS: It's a derivative of artemisinin, a common drug used around the world.

SCHLEGEL: We're starting a trial at Johns Hopkins. We're going to treat with the antimalarial and determine if it reverses the disease and eliminates it.

CONNIE TRIMBLE: It's formulated into a suppository.

HARRIS: Dr. Connie Trimble is running the drug trial at Johns Hopkins. Her main project is gearing up the human immune system to fight off cervical cancer.

TRIMBLE: This particular approach is completely different, and that's one reason I'm excited about it.

HARRIS: They're hoping this antimalarial drug will kill off precancerous cervical cells in women, sparing them from surgery.

TRIMBLE: If it works, this is a game-changer because it puts control of the treatment in the hands of the woman. In low-resource settings or settings where women don't have access to health care, they can do it themselves.

HARRIS: Doctors already know this malarial drug is safe, so it could be a front-line treatment in parts of the world where surgery simply isn't available. It would require an easy diagnostic test, but Trimble says that's also in the works. And cervical cancer is just the start. Dr. David Rimm learned about the Georgetown cell growing method when it was first published two years ago. And now, he's using it to generate cell lines.

DAVID RIMM: Well, it's pretty cool. We have over a hundred in our facility.

HARRIS: His lab is at the Yale University School of Medicine. Rimm says this is a huge step for research labs. It used to be he could only study a few different perpetually growing cell lines, and those were biologically pretty messed up.

RIMM: We can now have 40 or 50 cell lines from 40 or 50 different tumors from a population, and they all grow. And we can now do cell line type studies, but on populations of cell lines as opposed to two or three.

HARRIS: That gives him the same advantages as scientists get when they test new drugs on dozens of people instead of just a few. Dozens of labs around the world are now using this technique which is called conditional reprogramming of cells. And at the moment, everyone is hopeful that it will be the next big thing for studying diseases in the lab. But it is just a bit too soon to make that claim. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.