5 February 2009
Some years ago, Dr Caroline Gargett had what she thought was a ‘crazy idea’: take stem cells from the lining of a woman’s uterus, or endometrium, and engineer them into remedial tissue to treat pelvic organ prolapse, an all-too-common condition following childbirth.
Here she explains to Dr Andi Horvath how she was spurred on by the breakthrough discovery that a woman’s endometrium, which regenerates every month during the menstrual cycle, does so courtesy of two types of adult stem cells it contains.
These stem cells, the focus of Dr Gargett’s research, are now pointing the way to better treatments for both pelvic organ prolapse and endometriosis, where the endometrium grows outside the uterus.
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Transcript of podcast
Voice-over: Welcome to this special National Health and Medical Research Council podcast on ten of the best research projects for 2008. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.
Introduction: Hi I’m Dr Andi Horvath and I’m at the Monash University Department of Obstetrics and Gynaecology. I’ve come to the Monash Institute of Medical Research to meet with Dr Caroline Gargett. Caroline is the chief investigator of one of the NHandMRC projects entitled Targeting Stem cells To Treat Endometriosis. Endometriosis is a painful condition and is often the cause of some infertility. Let’s find out more about this project.
Interviewer: Caroline congratulations to you and your research team. Take us back in time. What was the premise of your investigation, what didn’t you know at the outset that needed knowing?
Dr Gargett: Well no one knew whether there was adult stem cells in the endometrium, no one had ever looked at this before.
Interviewer: Okay so we don’t know much about the endometrium, so how did you formulate your research investigations?
Dr Gargett: Well what we did know about endometrium which is the lining of the uterus, is that it’s highly regenerative tissue and it regenerates every month during the menstrual cycle. Most of it gets shed each month and then in about the space of say four to ten days about a centimeter worth of mucosal tissue grows. This is amazing growth and it occurs about 400 times in modern women over their reproductive years, so we reasoned that there must be adult stem cell population in the endometrium to mediate this massive cyclical growth just like there are adult stem cells in the skin and in the bone marrow and in the intestine, other highly regenerative tissues in the body.
Interviewer: So what are the outcomes of this research project, what do we know about the endometrium now?
Dr Gargett: Well what we do know is that there are two types of adult stem cell in the endometrium which we didn’t know about before. There’s an epithelial progenitor and this cell produces all the glands in the endometrium and those glands actually provide all the nourishment for the embryo for the first three months of pregnancy. We also found an adult mesenchymal stem-like cell that in the culture dish we can produce fat, bone and cartilage and smooth muscle just like the bone marrow type of mesenchymal stem cell. We also found other things about these cells. We found that they had the properties of adult stem cells like self renewal and differentiation and large proliferative potential and so that was fine but we also needed to find ways of isolating these cells so we could study them further and look at their role in diseases like endometriosis. So we’ve been able to identify several markers of the mesenchymal stem-like cell that enables us to separate them and prospectively isolate them and we now know where they’re located too in the endometrium and they’re located around the blood vessels both in the functional layer that gets shed with menstruation and in the basal layer that remains and therefore we know that those cells could be involved in growing new endometrium each month but those that are shed could well have a role in establishing endometriosis and that’s what we’re wanting to investigate now.
Interviewer: There’s still work to do?
Dr Gargett: There is plenty of work to do.
Interviewer: What is the impact of endometriosis on society?
Dr Gargett: Endometriosis actually strikes young women and these are the women in the prime of their life and they lose a large amount of working days, for example probably at least one day per month and often more so. Many have to undergo repeated operations. It’s very expensive for them so it’s a huge impact on women personally in their personal lives and also on the health care system and a recent study demonstrated that there was about 22 billion spent in the USA in one year on treating endometriosis and the trouble is those treatments are quite poor and it comes back, so within five years the majority of those women will have that endometriosis back again.
Interviewer: Caroline can you give us some stats on endometriosis?
Dr Gargett: About six to ten percent of women will have endometriosis and about two percent will have quite severe endometriosis where they’re quite disabled by the disease and for those in the infertile population, infertile women, about about sixty to eighty percent of them will have endometriosis.
Interviewer: Caroline if you could sum up why you do this research in one or two sentences, what would you say?
Dr Gargett: Well one is the scientific side of it that I’m really excited about the concept of adult stem cells and particularly in this very regenerative tissue and just to discover them and what their role might be, but the second thing is that really relates to perhaps translating this research to make a big difference for women’s health. Many women’s health issues and diseases are chronic, they are not very well treated and many women are suffering. Quite large proportions for example of endometriosis, six to ten percent of women, are missing large amounts of work time and they’re in huge amounts of pain, a lot of infertility, so we would like to make a difference there in finding novel and new ways of treating that disorder perhaps based on adult stem cells.
Interviewer: Tell us your expertise, where did you start off your scientific life?
Dr Gargett: I’ve had a very varied background and I have not come through the normal way. I had an academic career quite early on as a lecturer and I did a Masters Degree back then, then I had a family and completely took time out and went back again into academia but again as a lecturer without a PhD and finally in my 40’s I actually studied and did my PhD and in a completely different field, in haematology which has been my area of knowledge all along. But what that’s done is it’s given me the opportunity to bring that knowledge, including stem cell knowledge, into reproductive biology and I think that’s given us a real advantage in designing the project to begin with because I could read all the blood journals without being intimidated to get the basic information that we needed.
Interviewer: Introduce us to the other team members and the various research groups that you needed to recruit to get this investigation going.
Dr Gargett: Well I started off — this is a new investigator grant — so I started off with a very tiny group. I just had two students, PhD students, and the research assistant, part time research assistant, so I trained them in areas that I did know and we went on as a small group to work on this and then gradually we’ve recruited more people, particularly I needed people with expertise in small animal surgical areas and I’ve built up my team now to cover that, but we need expertise in flocytometry and fact sorting and working with human tissues and cell biology and general culture work and things like that so predominantly I have PhD students and now I’ve just got a post doc. and another one to come soon.
Interviewer: Caroline tell us about some significant events or significant people you’ve met.
Dr Gargett: Well one of the most significant things I think that really has helped this research go along was the fact that I received an award from the European Society of Human Reproduction and Embryology. This was quite a major award and I happened to be sharing accommodation in Hans Christian Anderson’s house with two professors from the Obstetrics and Gynaecology Department of Monash University. Those two professors took me out to dinner and they sat me down and they focused their whole attention on me and they said tell me your blue sky research ideas. This was quite an amazing thing for me. What I told them about was this crazy idea I had of taking the mesenchymal stem cell from the woman’s uterus or her endometrium and using it in a tissue engineering application for pelvic organ prolapse to support the herniated tissues that get damaged during childbirth and weaken then with ageing. Now that seemed a crazy idea so we sat around trying to work out how we might go about that. Now what’s happened with that particular incident is that we’ve obtained a small amount of funding, we’ve done a little bit of pilot data and that taught me that there were a number of things that we needed to do and I needed to go back to first principles yet again. That mentoring and that little bit of time that those professors gave me, gave me the courage to take on what seemed like a crazy idea through to at least the major grant stage.
Interviewer: Caroline some final reflections on being a chief investigator. Will you do it all again and why?
Dr Gargett: Ah well the thing about research is even though it’s long and hard work and quite repetitive is the excitement in discovery. I think discovery is really the most exciting thing and that’s what keeps you going. Those every now and then, that fantastic data that comes in, something unusual that you find, so that’s what keeps you going I believe.
The other thing I really enjoy watching is the development of your staff and students from really being quite inarticulate perhaps to being able to give prize winning presentations. It’s always a great pleasure when a paper is published and then we have had a number of awards along the way and that’s just the icing on the cake.
Interviewer: I’ve been speaking with Dr Caroline Gargett. She’s an NHandMRC, RD Wright Fellow. She’s also a senior scientist at the Centre for Womens Health Research, Monash Institute of Medical Research. Good luck with your research Caroline.
Dr Gargett: Thank you very much Andi.
Voice-over: This podcast was brought to you by the National Health and Medical Research Council working to build a healthy Australia. You’ll find more information about this and other health and medical research issues on our website at www.nhmrc.gov.au.