John Gearhart Interview (page: 5 / 8) Stem Cell Research	Print Interview

Where do you see as the next great frontier in this? There are so many medical implications of what you're doing.

John Gearhart: As you can imagine, the press has put us in a very awkward position. When we report scientific progress we are very conservative in what we're stating. We say, "Where are we right now?" Okay. Where we are right now is...

We have been able to demonstrate -- I mean, Jamie Thompson and myself using different procedures -- that you can isolate and have in culture these very important cells that have this ability of replicating in culture and then, under the right conditions getting them to -- what we call -- differentiate, or become specialized into different tissues. That's where we are. Where are we going right? Well, what we're trying to do right now is to identify the conditions under which you can take these cells and instruct them to only form one cell type. In other words, let's say you have a million cells in a dish of these embryonic stem cells and you say, "I want only dopaminergic neurons." Big term, but it's a specific type of a neuron and it's one that is clinically relevant because it's the one that's at risk in Parkinson's disease. Now how do we get all those cells in a dish to go in one direction? That is a difficult biologic problem. Or to form heart muscle? Or to form islet cells in the pancreas? Or anything else? So this is where we are going to be for the next ten years, figuring out the conditions under which you can take these cells that can form anything and saying, "But I only want this."
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One thing we haven't touched on is some of the medical implications of your research. We've heard about your interest in Down's syndrome. Can you tell us a little bit about how HPSEs can be a factor in tissue transplantation?

John Gearhart: If you have a cell in a laboratory setting that is capable of forming a variety of cell types, this opens up the possibility of culturing large numbers of specific cells that are at risk in a number of diseases. Now what we're talking about here are cells. We're not talking yet about organs, body parts or anything like this.

But there are many diseases that affect a single cell type, and that cell type is destroyed, whether it's Parkinson's, Alzheimer's disease, diabetes. Stroke for example, which will wipe out a region of the brain. There are a variety of neurons there, but some type of tissue transplant therapy would work. Or tissue damage, when someone accidentally cuts something or is burned or something like this.

Where there are specific cell types involved, it is reasonable to assume now that we can take these cells from a culture setting and transplant them into humans. Now it's actually more than reasonable. Proof of concept has already occurred in the mouse system, where the same types of cells have been isolated. They've been grown in culture to form, for example, all the blood cells. These blood cells then have been transferred into a mouse in which the blood producing capacity has been destroyed by radiation or chemicals. These cells -- these animals once they've been reconstituted -- are normal. Cardiac cells grown in culture have been placed in damaged mouse hearts, physically damaged, where they have integrated and have formed normal junctions and these hearts have been repaired. In the mouse, neural stem cells from these embryonic stem cells have been transplanted into the brains of animals and they have integrated and functioned.
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There's a very interesting clinical trial going on now in Pittsburgh in which these cells were first placed into an animal model of stroke and they ameliorated the effects of that stroke. Now these cells are being placed into stroke victims. So proof of concept is already there, so it will work. It absolutely will work, but when you start using it in humans you've got to be sure that all of the cells you have in that dish are the cell type that you want. So there are some other hurdles.

Isn't there a concern about rejection?

John Gearhart: Yes, certainly. Any time you transfer cells from one human being to another they'll be rejected unless you use these immunosuppressive drugs. Another advantage of these cultured cells is that we can genetically manipulate them to alter what we call cell surface determinants that your body responds to when they are different than yours. We can genetically manipulate them so that your body won't respond as, or won't respond at all. These cells give us that ability, so this is a very active area of research.

I feel that this work will only be successful if we can come up with what we're referring to as a universal donor cell. In other words, we would have banks of cells where we've genetically manipulated those genes that are involved in the rejection process so that they're compatible with a wide variety of people. It's a single bank and if you need cells of a certain kind you don't have to worry about them being rejected by anybody.

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