 Awesome. So today I want to introduce you to this organ here. This is the placenta. It's probably one of the most underappreciated organs in the human body, I think. But we should all stop and just give this guy a bit of credit because this is what kept you alive in utero for 40 weeks. And it did this by being a pretty amazing multifunctional organ. So it acted as your lung, as your gut absorbing both oxygen and nutrients in mum's blood. It acted as a bit of a kidney taking fetal wastes and excreting them back into the maternal circulation. And it was also a major endocrine organ regulating not only the baby's growth but adapting mum's whole physiology so that she was able to sustain that baby throughout the length of gestation. So this is a pretty incredible organ, but it's also probably the least understood organ in the human body. And that's a bit of a problem because in one in ten pregnancies this organ doesn't quite do what it should. So this leads to things like fetal growth restriction when baby's born too small. And it also leads to conditions such as preeclampsia which is mum gets dangerously elevated blood pressure. And these are especially a problem because it's actually very little we can do about these disorders. Usually what happens is that baby is delivered to remove the placenta and that usually happens before it should do in gestation. So my group's major research question is how does the hemipocenta actually form in normal pregnancy? Why does this go wrong so often and what on earth can we do about it? And when we're trying to approach these questions we actually really need to focus on the very early events in pregnancy. So the pathophysiology of pregnancy disorders is established often within the first 10 to 12 weeks of pregnancy. But understanding this in humans is exceptionally difficult. Obviously it's ethically and logistically impossible to get early implantation sites from human pregnancies. And we need to study this in humans because actually most laboratory animal models don't have the same anatomical structure as a human placenta. So we've gone about tackling this problem by looking at the stem cells from which the placenta is formed. There are two types of stem cell populations that I work with, tropholus stem cells and mesenchymal stem cells. So to explain a little bit about what on earth these are, let me just talk you through the placenta a bit up here. So you can imagine the placenta like a branching tree and if you were going to take a crust section through one of the nice leafy branches at the end, this is what you'd see. On the outside here you have mum's blood circulating around and what you can see largely in blue here are the trophoblast layers. So these are responsible for taking the nutrients from mum's blood and bringing them into the placenta. And so when we look at trophoblast stem cells we're trying to understand how these different types of trophoblast form and how they're doing that, drawing up the nutrients into the placenta properly. Then if we look on the inside we can see in green here this developing system of blood vessels. So this is an early gestation placenta we're looking at here. And as we develop throughout gestation, we'll get to the next slide somehow, as we develop throughout gestation this network continues to develop and become extensively branched so that it sort of maximizes the ability to take these nutrients, the trophobusters, drawing up and transfer them through the umbilical cord to the fetus. And what we think mesenchymal stem cells are doing in the placenta is playing really key roles in both forming these blood vessels at the start of pregnancy and regulating how they branch and expand throughout pregnancy to optimize that process. I really can't get the slides going here. Awesome. Thank you. Go. And we know that this process of blood development, blood vessel development is really important because this is one of the key things that can go wrong in growth restriction. So in growth restriction babies we're not getting enough nutrients transferred into the placenta and we're not getting enough uptake into the fetal circulation. So let me start by talking a little bit about the work we've been doing on human trophoblast stem cells. The major problem when working with human trophoblast stem cells is that we actually don't have a human trophoblast stem cell that's been isolated and characterized to work with in vitro. So a bit of a stumbling block. Mouse trophoblast stem cells were isolated more than 15 years ago and we have this amazing knowledge of all the cell differentiation events happening in the mouse placenta. But as I said we need to know how this relates to the human and what's actually relevant from that data to what we can apply to the human pregnancy. So sort of for the last four to five years I've really focused on trying to pull out the first human trophoblast stem cell so that we can understand what's happening in early pregnancy so that we can learn what's important and what's not important. So to do this I've taken a characteristic of most adult stem cell populations so the stem cells that kind of live in all of your tissues and play roles in regeneration and repair and this is that they like to survive better than all the other cells in the tissue. So if you put a toxin near them they spit it out really quickly. And that's exactly what we can see, yeah it's buzzing at me now, that's exactly what we can see up here. So we've put a fluorescent toxin essentially near these cells and the low standing intensity streak you can see is those cells spitting it out fast and we can separate out those cells. I've shown that they're 99% trophoblast so they're the kind of cells we want and they also when we profile the gene expression of these cells they express markers characteristic of other types of stem cells as well as mouse trophoblast stem cells and very early trophoblast lineage is in the placenta. So they look and smell like we would hope a human trophoblast stem cell would look and smell and that's really exciting. We can also isolate these from both early gestation placentas and from term placentas. So early gestation placentas are going to let us understand how the placenta grows and develops but actually I'm more excited about the fact we can get these out at term because this means we can take a normal placenta and a growth restricted placenta and this is exactly what we're doing in the lab at the moment and we can take the stem cells from those placentas and we can hopefully understand how they got to be like they are so how that pathology developed earlier in gestation. So mouse and camel stem cells are my nice easy stem cell to work with. There's a lot of data in the literature characterizing these cells. We know exactly what they should express on their cell surface so we can characterise them and show that the cells we've pulled out are mouse and camel stem cells. We can again isolate these from both first trimester and term placentas and I'm really interested in knowing how these cells contribute to that vessel development at the start of pregnancy, how they interact with the vessels throughout pregnancy because they actually live right around those vessels in the placenta and we think they secrete things that contribute to their ability to branch out extensively and why this goes wrong in fetal growth restriction. So in the popular press, mouse and camel stem cells often receive attention because of their roles in regenerative medicine and they kind of do some really neat things. So if you took a cardiac setting and a lot of this work has been done in the cardiac field and you induce something called a cardiac infarction so you damage an area of that cardiac tissue and you transplanted mouse and camel stem cells into that tissue what they would do is actually work to help heal and repair that tissue and they would do this in two ways. They would do it by improving angiogenesis so stimulating blood vessel growth and also by acting in an immunomodulatory way so dampening inflammation in that tissue and that's been shown to have clinically significant effects in improving the sort of regeneration and function of the heart. What I think is even cooler is that if you took a patient that had a cardiac infarction and actually not inject the cells into the tissue just inject them into the main circulation then what those cells would do is hunt out that area of damage in the body home there and then have those actions. So they're quite remarkable and placenta and mesenchymal stem cells have been used in this kind of way to treat other organs and actually what I want to know is could they be used on the organ from which they come so could we use placental mesenchymal stem cells to treat problems in placental development and blood vessel growth, areas of infarction in the placenta areas of sterile inflammation that we sometimes see in these growth reciprocating cases. That seems a little bit out there I guess so that's going to involve transplanting stem cells into a baby in utero but actually this is on the medical horizon at the moment so the first trials injecting mesenchymal stem cells in utero are already starting in the states to treat osteogenesis imperfecta so this is definitely something we could feasibly look at in the future but of course first we need to have some solid, solid science behind it so we've started out looking at this in vitro so what you can see here are that we've injected fluorescently labelled mesenchymal stem cells into chunks of first trimester and term placental tissue and when we do this what we see is that they branch out and form these networks throughout the tissue so they migrate throughout the tissue and they also scoop around the blood vessels so they're homing to their natural niche where they would live in vitro and that's excellent because that's exactly what we would want them to do if we were transplanting them in vivo so what we're now trying to figure out is actually what they're doing once they get there what are they secreting how are they going to influence those vessels and could we then take these cells into an in vivo model and see if we can actually rescue a growth-rejected phenotype by transplanting mesenchymal stem cells in there so all that remains is to hope that I've generated some level of excitement in the audience about placental stem cells and to thank the people that give me money to play around and do this and all my collaborators and students that have contributed bits along the way