Stem Cells and 'Stemness'

Chris -   Now we've been talking about stem cells this week in a big way, and someone who works on them is Roger Pedersen, he's from Cambridge University.  Hello Roger,

Roger -   Hello.

Chris -   Now listening to what Claudio Stern was saying to Meera there, the bottom line is then you have stem cells in tissues, those stem cells are there to make new cells in that tissue when the cells clap out and die.  I guess the key question is then; how do those cells become specialized to do that job in the first place?

Roger -   So, indeed, stem cell biologists start with this question:  What is 'stemness'?  That is to say what sets stem cells out and makes them special?  And that, as you've been hearing from Professor Stern, is the ability of unspecialised cells to renew themselves as unspecialised cells but still retain this ability to specialise.  That's a very special quality, we call it stemness.  Why this is important in out bodies is that this enables our bodies to replace cells, the specialised cells that either get worn out or get damaged.  It enables them to replace them and to renew our tissues using the unspecialised cells that are present in those tissues.  That's why we last as long as we do.

Chris -   So if you have, say if you look at your skin, there will be a population of cells in the base of our skin which are stem cells and know how to make not only new skin stem cells, but also new skin cells.

Roger -   That's in fact the case.  The cells in our skin that are stem cells are scattered throughout our skin, and there are probably some in our hair follicles too.  Certainly a lot of hair follicles in a mouse and we know for example there are a lot of stem cells in the follicles.

Chris -   So are those skin stem cells then different to the stem cells that will be in my bone marrow, making new blood cells, and can they swap places and do the same job?

Roger - The stem cells in our skin are almost certainly different than the stem cells in our blood, and that's why our skin makes skin on the outside of us instead of blood.  But what we want to know is what do they share?  What's this property of stemness that's shared between the skin and the blood?

Chris -   And presumably can you swap them round?  Can you persuade a bone marrow stem cell, which is easy to get at to become a cell that might be able to be a precursor for cells that make insulin in the pancreas, so you could maybe turn a diabetic pancreas into a normal pancreas?

Roger -   Well, to make them useful, stem cells of any kind would be fantastic if you could swap them around like that.  Some people say they think you can, but many other people believe you can't.  

Chris -   So there are many different types of stem cells then, and they're specialised to the job that they do in that bit of the body.

Roger -   Indeed.

Chris -   But do they understand how they actually get specialised to do that, because that's a big question, isn't it?

Roger -   Well right now we're just beginning; we're just scratching the surface to understand what this stuff, this stemness, is.  And it seems to be the postponement of the decision about what to be.  That is to say the ability to sustain ambiguity, to make a decision later on.  And that's a special state of the genes and the DNA in the cell.

Chris -   But to what extent is it due to the environment in which a cell finds itself?  If I transplant a skin stem cell to my bone marrow, do the cells around it say "Hey, you're in the bone marrow now, so stop behaving as a stem cell and start being bone marrow-ish".  Or does it still try and make skin in the bone marrow.

Roger -   Well I don't think that exact experiment has been done, people have in fact placed blood stem cells in other places and found that they only made blood.  

Chris -   Do we know why these cells make these decisions to say right, I am going to be a skin stem cell?  How is that achieved?  Because that sort of says that sort of cell is now hard wired to do one job, which is intriguing isn't it?

Roger -   I think to answer your question the environment is extremely important, and the environment that keeps the cells in early development from specialising is an environment like GCSE-era which keeps you from deciding whether to be a surgeon or a GP.  In other words, that's a decision they have to make later, so they aren't exposed to that decision early on.

Helen -   I think one of the questions on a lot of people's minds with stem cells is in relation to the applications, the medical applications that they might actually have in the future.  I take it at the moment we aren't using them for any diseases right now, but perhaps we would in the future?

Roger -   Well actually I should correct this impression that stem cells aren't used in therapy.  Blood stem cells have been used in therapy for well over a decade, and will continue to be.  Many patients have bone marrow stem cell transplants.

Helen -   Is that for leukaemia?

Roger -   For leukaemia and other diseases.  However, the question is when will the other kinds of stem cells be used, and in particular I'm interested in the stem cells that come from very early stages of development, that come from, in fact, growing fertilised eggs in the Petri dish from in-vitro fertilisation patients.  These surplus fertilised eggs can be developed into what we call embryonic stem cells, that seem to have the widest possible ability to specialise into useful tissues.

Chris -   So in other words, they haven't made decisions to be any particular part of the body, or they've made fewer decisions, and therefore they can turn into more things at that stage.

Roger -   They haven't made any decisions except, perhaps, deciding not to be a placenta.

Chris -   Right, so how do you turn those cells into the bits of the body you want, and are we able to do that yet?

Roger -   Well that's what we're trying to figure out actually.  And in fact we do have some answers but not all of them.  It seems that it's a mixture of decisions made by the environment based on the presence of certain things, proteins that make them make decisions, and on the absence of other things.  So the absence is just as important as the presence of things.  

Helen -   And going back to the therapeutic side of stem cells, what kind of things do you think we might be able to work towards in terms of treatments based on stem cell technology?

Roger -   So it almost seems certain that the earliest clinical applications that are relevant are going to be not actually based on transplantation, as most people think, but the use of stem cells to discover new drugs, or test the effectiveness or toxicity of new drugs which are developed for treatment of people.  In other words just using the cells to develop them in the Petri dish and test those nerves, or heart cells, or liver cells.

Helen -   Is that kind of replacing animals as a subject in terms of drug testing and so on?

Roger -   Well indeed, I think this is one of the most likely and one of the most intensive uses of stem cells.