The Use of Stem Cells for Therapeutic Purposes: A Case Study for Middle School Students Bryan Nicklaus Brown, BS NIH NSRA F31 Predoctoral Fellow McGowan Institute for Regenerative Medicine Department of Bioengineering University of Pittsburgh AND Rosa Lynn Pinkus, PhD Professor Medicine/Neurosurgery Associate Director, Center for Bioethics and Health Law Director, Consortium Ethics Program University of Pittsburgh Note to Teachers: This module utilizes and builds upon the moral and ethical concepts and problem solving methods described in “The Use of Animals for Educational and Research Purposes: A Case Study for Middle School Students”. Teachers are encouraged to use the previous module as a simple “example” case before asking students to consider the more complex ethical dilemma presented in this module. Also, teachers are cautioned that this module deals with more complex and “adult” issues than the previous module. As such, you should tailor the specific details of the case to the demographics of your class. Joe is considering applying for graduate school. He knows that he really wants to work on something that will help people in a big way and sets about looking for schools that are involved in research that has the potential to make a real clinical impact. In his search, he comes across a university that is pioneering the use of cardiac tissue engineering to develop new therapies to help patients with heart disease. Specifically, the research is directed at helping people who have suffered heart attacks and lost heart muscle function. Joe knows that heart disease is not only a big problem, affecting millions of patients in the United States, but also that it runs in his family. In fact, his uncle suffered a heart attack less than a year ago. With this in mind, Joe decides that he would like to get a PhD in biomedical engineering and focus his thesis research in the cardiac tissue engineering lab of the university he has identified. His grades are excellent as are his GRE scores. His undergraduate advisor writes him supportive letters of recommendation. He applies to three schools and gets an interview at the university. In preparing for the interview, he does more background research about the laboratory that is doing the cardiac work. He learns that they use embryonic stem cells and collagen to repair damaged heart muscle following a heart attack. The research is considered to be very promising, and a number of scientific journals, newspapers, blogs, and TV programs begin to highlight the promise it holds for patients. Joe’s family, friends and neighbors have seen these reports and are excited that Joe may actually become part of the team that is working on the project. 1 In particular, Joe’s uncle has become interested in heart tissue engineering since he recovered from his heart attack. He sends Joe this article about the work being performed in the lab at the university to which he is applying: Embryonic Stem Cell - Based Tissue Engineering May Help Repair Damaged Heart Muscle Embryonic stem cells may hold the key to regenerating damaged heart muscle, when transplanted within a 3-dimensional scaffold into the infracted heart, according to a new study coming out in June in the Journal of Heart and Lung Transplantation. In the study, embryonic stem cells were more successful in restoring heart muscle when transplanted within a 3-dimensional matrix into damaged hearts in an animal model of severe infarction. The new study addresses several problems that have plagued previous attempts to regenerate damaged heart muscle, according to Theo Kofidis, M.D., who has an active tissue engineering program at Stanford. "Tissue engineering holds out promise of truly healing the heart after congestive heart failure," said Dr. Kofidis, lead author of the study and research fellow in cardiothoracic surgery at the Falk Research Center at Stanford University Medical School in Stanford, Calif. "There are 460,000 cases of congestive heart failure in the United States each year and the preeminently efficient treatment we have at this time is heart transplantation. Through tissue engineering we could actually restore the function of the heart by replacing large portions of the damaged heart muscle by a bioartificial one." Kofidis and his colleagues had been working with bone marrow stem cells, but these cells were not able to become heart muscle cells and regenerate the heart. "In our most recent studies we showed that mouse and human embryonic stem cells improved heart function, had superior survival within the heart – weeks later we still saw improved heart function – and had definitely differentiated into heart muscle cells," he said. "We inserted a bioluminescent marker (what causes fireflies to luminesce) into our stem cells and were able to see that they engrafted in the living organ." There are two components to tissue engineering, according to Dr. Kofidis: the cells that will replace the dead cells and regenerate the organ, and the supporting framework that will distribute the cells evenly and maintain the 3-D shape necessary for proper functioning of the organ. "We have been working for a long time on developing the ideal scaffolding to support the injected cells and the architecture of the organ," said Dr. Kofidis. "We have identified a collagen, a mesh-like structure, that we have manipulated into an excellent framework. The cells distribute evenly into this meshwork, which is a liquid. Then, due to its liquid nature, we are able to inject it into the heart through an endoscope, with much less surgical trauma than if we had to open the chest to reach the heart. This liquid tissue solidifies at body temperature. "We let Nature integrate this tissue," said Dr. Kofidis. "We inject it as a liquid and let it consolidate within the affected heart where it supports the geometry of the damaged region. One of the problems in congestive heart failure is that the wall of the heart's chamber becomes thinner and thinner as the heart muscle cells die off. Eventually it is too weak to beat properly." With the integration of the human embryonic stem cells and their patented supporting framework, Kofidis hopes that they have the two pieces of the puzzle needed to successfully integrate regenerative cells into the damaged heart, maintain its geometry and restore its function. "A word of warning may be appropriate here. Only a few years ago many people thought an artificial heart was around the corner," said Dr. Kofidis. "We now know that there are many problems to overcome and questions to answer. In order to reproduce nature with the highest possible fidelity we have to build something that follows the natural architecture of the heart.” 1 Note to Teachers: This is only one of many examples of scientists using stem cells to develop regenerative therapies. Teachers are encouraged to supplement the above article with additional articles that further illustrate the use of stem cells in research, describe the ethical concerns associated with their use, or involve local researchers/patients in order to provide students examples to which they can relate. 1 Article adapted from: Embryonic Stem Cell - Based Tissue Engineering May Help Repair Damaged Heart Muscle. ScienceDaily (May 18, 2004). Online: http://www.sciencedaily.com/releases/2004/05/040518075414.htm 2 A few weeks before his interview, Joe’s uncle tells him how excited he is that Joe might soon be participating in the kind of research he read about in the article and wonders if a regenerative medicine treatment might have helped to speed his own recovery? Joe says “I think that the research that they are doing is great. It sounds like the embryonic stem cell treatment they are using is working and can help people. I really hope that I can get into the lab.” Peggy, overhearing the conversation that Joe is having with their uncle, becomes interested. She has been learning about the reproductive and developmental process in her science class. She knows that, during reproduction, an embryo is a cluster of cells that eventually goes on to become a baby animal, or person. She is confused, though, about what exactly a stem cell is, and how they get them from an embryo to use in research and asks Joe to explain. Note to Teachers: This is a good opportunity to stop and do an activity related to the development and biology of reproduction/embryos, if it has not already been covered in class. This is also a good opportunity to discuss the source of the embryos for research purposes (i.e. embryos remaining from in vitro fertilization). Teachers are referred to ??? (Dr. Pinkus, can you please fill in the name/pg number of the NIH materials that we have for this?) for more detailed information on this subject. You are encouraged tailor the content of this discussion to fit the maturity/demographics of your students. Joe explains, “You’re right. An embryo is a cluster of cells that has the potential to continually divide and differentiate to become an animal or a human. Scientists are able to collect cells from a part of an embryo that have the ability to develop into a variety of different types of cells in the body. These cells are called embryonic stem cells” “Are all of the cells in an embryo stem cells?” asks Peggy. “No, only some of the cells in an embryo are stem cells. The other cells aren’t. Scientists have to use special techniques to separate the stem cells from the other cells.” “Oh. So, what’s the difference between the stem cells and the other cells?” “That’s a very complicated question, but let me see if I can answer it. Stem cells are unspecialized cells that can make exact copies of themselves by dividing and can also turn into more specialized cells like bone cells or skin cells. Other cells are already specialized cells and can’t become another type of cell. For example, a cell that has already turned into a red blood cell can’t become a skin cell, but a stem cell can become a blood cell or a skin cell. Does that answer your question?” “I think I get it. But, what do stem cells do, exactly? Why are they so important?” “Well, like I said, they can create copies of themselves and turn into other types of cells in the body. This how they are able to divide and create new cells as we develop from an embryo. But stem cells aren’t only in embryos, adults also have stem cells that keep working as we get older.” “Really?” “Really. For example, our skin cells are dying and being replaced every day. There are stem cells in our skin that divide and produce new cells that turn into skin cells. This allows the skin to keep growing and protecting our bodies, even if some of the cells die or get damaged.” “In class we learned that our blood cells only live for a little while and have to be replaced all the time. Are we able to do this because of stem cells too?” “Yes, I think you’ve got it. Blood cells only live for about four months and our blood cells are dying by the billions every day. These cells have to be replaced to make sure that we have enough blood cells left to live. Actually, if you think about it, in four months every blood cell in your body right now will be gone. This is possible because we have stem cells 3 in our bone marrow that are able to create enormous numbers of blood cells that replace the ones that die. In fact, lots of our organs have cells that are dying and being replaced twentyfour hours a day. Stem cells allow us to create the specialized cells that we need to replace dying cells by dividing and then turning into more specialized cells like those in the blood or on our skin.” “Wow. I didn’t realize that stem cells could do so many things. Does this mean that if a scientist has a stem cell, he can make enough cells to replace any part of our bodies? That would be really cool, and I bet it would help a lot of people.” Note to Teachers: This is another good time to stop and highlight examples of the types of treatments being developed using stem cells. You can ask your students to discuss whether or not they would undergo a stem cell therapy and why. You can also ask students to discuss whether it is acceptable to use stem cells in life saving, life improving, or cosmetic/performance enhancing therapies. Is it more acceptable to use stem cells in one case than in another? Does it depend on the source of the stem cell (see the provided Ethics and Stem Cell primers for a description of various stem cell sources)? You can ask your students to answer these same questions again after completion of the module to see how their opinions have changed and why. “That would be really cool, but it’s a lot more complicated than that. Scientists have to treat stem cells using very complex methods just to get them to divide and change into the type of cells they want. It has taken many years just to figure out how to collect them and prove that they can do all of these things. Scientists are only just now learning how to use them as treatments for people and there are a lot of questions that still have to be answered.” Peggy, now with a better understanding of what an embryonic stem cell is and where they come from asks Joe, “Wait, do scientists have to destroy the embryos to get stem cells out?” “Usually,” says Joe. “Isn’t this the same thing as destroying a life? An embryo is the beginning of what eventually becomes a living animal or person, right? If they destroy it, it can never go on to become a living animal or person. I know that the research is meant to help patients, and it sounds like it really works, but is it right to destroy life?” Note to Teachers: This is a potential “red-flag” issue. The debate over the use of stem cells is driven by many views and opinions. Students should be encouraged to speak with their parents, siblings, teachers, and/or religious leaders, etc. to help them form their own opinions about the topics of “when life begins”. Teachers are encouraged to refer to the provided Ethics and Stem Cell Primers for more information on how to approach this question with students. Also, if you feel that a discussion of the subject of embryonic stem cells is inappropriate for your class, there are a number of other types of stem cells that may be examined instead of embryonic stem cells. Information on these cell types may be found in the Ethics and Stem Cell Primers that accompany this material.) “I guess I hadn’t really thought about that too much. I was just focusing on how much good these cells might be able to do for people.” “It sounds like they might be able to help a lot of people. But, couldn’t an embryo become a person? Aren’t there any alternatives?” “Actually, now that you mention it, there are a number of alternative sources of stem cells. But each one has its own scientific and ethical questions that must be answered before they can be used to develop a treatment.” 4 Note to Teachers: This case raises a number of questions about stem cells, their sources, and how they are used. You should choose which of these questions is most appropriate for your class to examine. Some suggestions: Discuss both the scientific and ethical considerations involved with the use of multiple types of stem cell (see the provided Ethics and Stem Cell primers for more information regarding the different types of stem cell, their sources, and ethical and scientific considerations). Have students split into groups and have each one present the considerations associated with one of the types of stem cell. Ask students to identify the ethical dilemmas and the types of moral and ethical reasoning associated with each type of stem cell. Ask students to create lists of the “Pros” and “Cons” associated with each type of cell. Ask students to use the line drawing techniques presented in “The Use of Animals for Educational and Research Purposes: A Case Study for Middle School Students” to organize and analyze their thoughts about each cell type (see the Harris text for a more in-depth description of the line drawing technique). Ask students to discuss how their opinions about the use of stem cells changed following a discussion of the ethical and scientific considerations associated with their use. Ask students for examples of how they think stem cells could be used to help people in a way that they think is ethically acceptable. 5