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Medical Research Council - MRC podcasts, Professor Michael Schneider talks stem cells

In this MRC podcast, leading stem cell scientist Professor Michael Schneider, Head of Cardiovascular Science at the National Heart and Lung Institute at Imperial College shares his opinions on the importance of public dialogue and the future of stem cell research with MRC press officer Laure Thomas.

LT: Professor Schneider, this has been the year of the stem cell; why is it important to continue having these dialogues with the public?

MS: AS with any rapidly evolving medical therapy, there are important ethical issues to be discussed. One of those which is particular to the stem cell debate concerns public attitudes towards the use of embryos to generate the cells that are then used for human therapies.

LT: And why is it that we can't use adult stem cells as has been shown recently, to carry out these therapies? MS: Well that's a terrific question and in my lab, work goes on in parallel with adult stem cells that we purify from the heart as well as with human embryonic stem cells. And I think it's important for both to be studied. Human embryonic stem cells have the greatest capacity to turn into all cells types that might be needed clinically without exception. Adult stem cells taken from different organs might be predisposed to turn into particular cells, like cells of the heart and blood vessels in the case of the ones that come from the heart. Occupying the middle ground between those two is the so called induced pleury potent cell which can be engineered from a patient's own skin cells for example, using a cocktail of genes that make embryonic stem cells so particularly stemmy. The fact that induced pleury potent cells can be made, that can be turned into a large number of cell types, gives encouragement to the idea that these might be used to overcome the transplantation barrier and in addition if proven to be successful in all applications, might come in time to supersede the need for human embryonic stem cells. But two points need to be emphasised; the first is that the induced pleury potent cell is a wholly artificial construct that's made by artificially expressing a small number of genes at unusually high levels. Consequently the conversion of those cells into the different cell types of the body really can't be studies in precisely the same way as the real human embryonic stem cell can. It might lack fidelity to normal development, to normal maturation in one or more key ways. So as a test bed to learn how the different parts of the body form, it's different. The second is that ultimately the test for any cell product regardless of its origin is going to be not just what kind of cell it makes, but precisely how functional, precisely how mature those cells become. It's far from proven that induced pleuripotent cells would make cardiac myocites that beat as vigorously as normal ones or that human embryonic stem cells would make cardiac muscle that beat as vigorously as normal heart muscle cells do. So this is going to require a lot of cell biology, a lot of tissue engineering, a lot of imperical testing of these cells in a variety of different conditions and it's ultimately going to be a race determined by which cell works best in a particular context. LT: There are a number of risks involved with stem cell therapies, high levels of risks probably. How do we go from the bench to the clinic in as safe as possible a way?

MS: That's a wonderful question and it actually raises a point where different opinions in the public come into conflict with one another. On the one hand no physician and no patient would want a treatment to go into humans that hadn't been proven to be completely safe. On the other hand the path to proving that a treatment is safe ultimately requires validation in a large mammal. Those two goals are inherently in conflict with one another, developing and testing in humans only those therapies that are proving to be safe and on the other hand, avoiding large animal research.

LT: And what do you foresee for 2009 in terms of stem cells? We've had a very busy year in 2008, what's the next step? MS: So in 2009 we can expect the pace for stem cell research of all kinds to pick up even further. It's the single most exciting development in my field, in my professional career. At the very basic level we can expect discoveries in terms of how embryonic stem cells and adult stem cells proceed to become the different kinds of cells that are needed clinically. We can expect additional studies in animals proving that the engraftment of stem cells can rescue organ function in different circumstances. Although clinical trials of human stem cells may see far off and futuristic to some of your audience, in the cardiovascular field more than a dozen human trials have been reported worldwide, typically with bone marrow and the results are encouraging. But there clearly are ways to improve the outcomes, either by making those bone marrow cells more active or by supplanting them with cells that turn into heart muscle more efficiently. And so both at the bench and in the clinical trials we can expect a lot in the coming year.

If you'd like to read more about public opinions of stem cell research, you can download a copy of the stem cell dialogue report from our website, visit mrc.ac.uk. LT: Laure Thomas MS: Professor Michael Schneider

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In this MRC podcast, leading stem cell scientist Professor Michael Schneider, Head of Cardiovascular Science at the National Heart and Lung Institute at Imperial College shares his opinions on the importance of public dialogue and the future of stem cell research with MRC press officer Laure Thomas.

LT: Professor Schneider, this has been the year of the stem cell; why is it important to continue having these dialogues with the public?

MS: AS with any rapidly evolving medical therapy, there are important ethical issues to be discussed. One of those which is particular to the stem cell debate concerns public attitudes towards the use of embryos to generate the cells that are then used for human therapies.

LT: And why is it that we can't use adult stem cells as has been shown recently, to carry out these therapies?

MS: Well that's a terrific question and in my lab, work goes on in parallel with adult stem cells that we purify from the heart as well as with human embryonic stem cells. And I think it's important for both to be studied. Human embryonic stem cells have the greatest capacity to turn into all cells types that might be needed clinically without exception. Adult stem cells taken from different organs might be predisposed to turn into particular cells, like cells of the heart and blood vessels in the case of the ones that come from the heart. Occupying the middle ground between those two is the so called induced pleury potent cell which can be engineered from a patient's own skin cells for example, using a cocktail of genes that make embryonic stem cells so particularly stemmy. The fact that induced pleury potent cells can be made, that can be turned into a large number of cell types, gives encouragement to the idea that these might be used to overcome the transplantation barrier and in addition if proven to be successful in all applications, might come in time to supersede the need for human embryonic stem cells. But two points need to be emphasised; the first is that the induced pleury potent cell is a wholly artificial construct that's made by artificially expressing a small number of genes at unusually high levels. Consequently the conversion of those cells into the different cell types of the body really can't be studies in precisely the same way as the real human embryonic stem cell can. It might lack fidelity to normal development, to normal maturation in one or more key ways. So as a test bed to learn how the different parts of the body form, it's different. The second is that ultimately the test for any cell product regardless of its origin is going to be not just what kind of cell it makes, but precisely how functional, precisely how mature those cells become. It's far from proven that induced pleuripotent cells would make cardiac myocites that beat as vigorously as normal ones or that human embryonic stem cells would make cardiac muscle that beat as vigorously as normal heart muscle cells do. So this is going to require a lot of cell biology, a lot of tissue engineering, a lot of imperical testing of these cells in a variety of different conditions and it's ultimately going to be a race determined by which cell works best in a particular context.

LT: There are a number of risks involved with stem cell therapies, high levels of risks probably. How do we go from the bench to the clinic in as safe as possible a way?

MS: That's a wonderful question and it actually raises a point where different opinions in the public come into conflict with one another. On the one hand no physician and no patient would want a treatment to go into humans that hadn't been proven to be completely safe. On the other hand the path to proving that a treatment is safe ultimately requires validation in a large mammal. Those two goals are inherently in conflict with one another, developing and testing in humans only those therapies that are proving to be safe and on the other hand, avoiding large animal research.

LT: And what do you foresee for 2009 in terms of stem cells? We've had a very busy year in 2008, what's the next step?

MS: So in 2009 we can expect the pace for stem cell research of all kinds to pick up even further. It's the single most exciting development in my field, in my professional career. At the very basic level we can expect discoveries in terms of how embryonic stem cells and adult stem cells proceed to become the different kinds of cells that are needed clinically. We can expect additional studies in animals proving that the engraftment of stem cells can rescue organ function in different circumstances. Although clinical trials of human stem cells may see far off and futuristic to some of your audience, in the cardiovascular field more than a dozen human trials have been reported worldwide, typically with bone marrow and the results are encouraging. But there clearly are ways to improve the outcomes, either by making those bone marrow cells more active or by supplanting them with cells that turn into heart muscle more efficiently. And so both at the bench and in the clinical trials we can expect a lot in the coming year.

If you'd like to read more about public opinions of stem cell research, you can download a copy of the stem cell dialogue report from our website, visit mrc.ac.uk.

 

LT: Laure Thomas
MS: Professor Michael Schneider