Engineering Endometrial Tissue

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Hans van der Slikke, MD, PhD: "It's October of 2001, and we're in Orlando, Florida at the ASRM. Next to me is Professor Liu, and she's the Head of the Endocrinology Lab in Cornell University, Cornell Medical School. Welcome, Professor Liu."

Helen Liu, PhD: "Thank you very much."

Hans van der Slikke, MD, PhD: "You had a very exciting presentation about your biotechnology efforts in seeding endometrial cells in a matrix. Can you tell me the advantage and the meaning of this?"

Helen Liu, PhD: "In the past I tried to develop a co-culture with an embryo in a monolayer of endometrial cells for study, and we found a lot of important information out of that. First of all, they can enhance the endometrial reliability and more importantly they can improve the pregnancy of the IVF patient. This is very exciting and now this co-culture system is used routinely in IVF patients. But if I wanted to use this system for studying the mechanism of implantation I ran into problems because the monolayer of endometrium doesn't provide room for embryo penetration and invasion so I thought I should construct a three-dimensional human endometrium tissue for co-culture then I could simulate implantation in vivo."

Hans van der Slikke, MD, PhD: "I see, so you had this three-dimensional tissue, what did you do as the next step?"

Helen Liu, PhD: "The next step was to look into the literature and I found that a lot of people have done vitro engineering in different fields so I adapted this concept to my field. I used a matrix and this matrix is a copolymer; it's composed of two natural substances - one is chondroitin and the other one is collagen. The beauty of this copolymer is that when they grow, they form a three-dimensional platform so a cell can grow in there to be a three-dimensional tissue. The other thing is that this is biodegradable so when you culture for a long time they just dissolve or if you transplant it to the patient they will be reabsorbed so that's why I think it has a great application for the future."

Hans van der Slikke, MD, PhD: "Did you already do some tests with implantation?"

Helen Liu, PhD: "Yes, we successfully engineered human endometrium tissue which was composed of the glands and the stroma cells. Amazingly, those glands really mimic the in vivo structure. More importantly, we co-cultured with an embryo, and the embryo grows very happily and very healthy and they even remained grow-poe-ship and the characteristic of this embryo development is very similar to that in vivo. I have some slides to show you but I don't know whether you have a chance to show that to the audience."

Hans van der Slikke, MD, PhD: "Yes, we will show them."

Helen Liu, PhD: "So after five day's culture they reached the hatch stage as expected and after six days of co-culture then they were attached to the epithelium itself, simulating early implantation. I think it's very fascinating and very interesting and has a great future for this system."

Hans van der Slikke, MD, PhD: "This must have been a very exciting day for you, this sixth day. So you can now see the influence of these four kinds of hormones on the endometrium and the implantation. Is it kind of, let's say, science fiction to say maybe in the far future you could have a real breathing embryo and have a child in the laboratory?"

Helen Liu, PhD: "That's my final goal, I call it an ¨artificial uterus¨. I want to see whether I can develop an actual external device with this endometrium cell and then probably with a computer system simulate the feed in medium, feed out medium, simulating the abrupt stream and also have a chip controlling the hormonal level. Because throughout the whole pregnancy the hormonal level is changing, protein is changing, and the growth factor is changing. So I want to use a computer to help me do this, and I believe if this can be achieved, we could possibly have an artificial uterus so then you could grow a baby to term."

Hans van der Slikke, MD, PhD: "This will be very exciting."

Helen Liu, PhD: "This is a long term goal but I don't know how long it will take but I'm working in that direction."

Hans van der Slikke, MD, PhD: "Great, can we shift to another topic because I imagine that this kind of culture can serve several other goals. For example, women that don't have a proper lining of the uterus - do you think that there will be a possibility to seed new endometrium in the uterus?"

Helen Liu, PhD: "Yes, that's why we call it cell or tissue therapy. I hope if a woman has a problem with the endometrial lining, then if we culture and use this engineered tissue, we can transplant it to the woman and see whether it can help them for the implantation. Or if the woman has part of her uterus surgically removed, we can implant that to fix the uterus. Also, some patients like a DES patient who are born with a T-shaped uterus also has a problem on implantation, maybe we can make a so-called new organ for her and transplant it to her to fill the purpose of carrying the baby."

Hans van der Slikke, MD, PhD: "Another idea may be in cancer patients. Do you think with endometrial cancer that you can use it in a certain way?"

Helen Liu, PhD: "Yes, but this is a more advanced technology, you have to lump that with the microbiologist, you transect the cells before you introduce it to the organ. In other words, use gene multiplication, you introduce some kind of genes, which can produce anticarcinogenic agents and then this tissue engineers the tissue with modifying cells. You implant the two somewhere near the tumor and then they can secure the entire carcinoma agent to act directly on the tumor for integration. I think that's a great future and in animal studies it has been done and has been done successfully. I think this is a very important application in the future."

Hans van der Slikke, MD, PhD: "I think so and in conclusion, I would say it's a very, very broad field in reproductive endocrinology from early pregnancy until the early stage of carcinoma; it's a very broad view. It's very impressive and I want to congratulate you on your success so far, and I hope to hear some time in the future about your next success."

Helen Liu, PhD: "I hope so too and I'm working on that direction. Thank you very much."

Hans van der Slikke, MD, PhD: "Thank you very much."