NATIONAL QUALIFICATIONS CURRICULUM SUPPORT Biology/ Human Biology Case Study on Stem Cells Support Materials [HIGHER] The Scottish Qualifications Authority regularly reviews the arrangements for National Qualifications. Users of all NQ support materials, whether published by Learning and Teaching Scotland or others, are reminded that it is their responsibility to check that the support materials correspond to the requirements of the current arrangements. Acknowledgement Learning and Teaching Scotland gratefully acknowledges this contribution to the National Qualifications support programme for Biology and Human Biology. The publisher gratefully acknowledges permission to use the following sources: diagram of stem cell cultivation, illustrations produced by the Imaging Core, University of Kansas Medical Centre, www.kumc.edu; diagram of stem cell cultivation © University of Wisconsin-Madison, image used with permission; diagram of the skin, taken from CancerHelp UK, the patient information website of Cancer Research UK, www.cancerhelp.org; article ‘Neuron breakthrough offers hope on Alzheimer’s and Parkinson’s’ from The Times Online, 28 January 2010 © Hannah Devlin/The Times/NI Syndication. Every effort has been made to trace all the copyright holders but if any have been inadvertently overlooked, the publishers will be pleased to make the necessary arrangements at the first opportunity. © Learning and Teaching Scotland 2011 This resource may be reproduced in whole or in part for educational purposes by educational establishments in Scotland provided that no profit accrues at any stage. 2 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 Contents Activity 1: An introduction to stem cells 4 Activity 2: An introduction to stem cell research and regulation 9 Activity 3: Therapeutic use of stem cells 15 Activity 4: Roslin Cells video 28 Activity5: The great stem cell debate 30 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 3 ACTIVITY 1 Activity 1: An introduction to stem cells Teacher’s notes Area of curriculum Higher Biology Unit 1 – 2 c i, ii Higher Human Biology Unit 1 – 1 a Aim The aim of this activity is to introduce the students to what stem cells are and where they originate. It also introduces them to their value as thera peutic agents. Suggested delivery and lesson plan The PowerPoint can be used to introduce the basics of stem cell biology , which should take approximately 15 minutes. However, the focus of the lesson should be to generate discussion and encourage the dev elopment of research skills. It is suggested that the slides of the focus questions at the end of the PowerPoint are printed out and used for group work. Each group could be allocated a question and then nominate a person to feed back to the class. Each student could then fill in the answer from each group into their own sheets. This should take approximately 15 minutes. The last slide of the PowerPoint allows for another group task for which students can get the information through discussion or access to appropriate level biology books or the internet. It should be stressed to the class that the media is an important way in which information can be communicated to the public. Each group could prepare an A4 leaflet containing the information required that could be used for class discussion at the next lesson. 4 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 1 Knowledge and skills Introduction to stem cell biology Expansion of vocabulary of biological terms Explore some physiology Opportunity to revisit gene expression in Higher Biology Sets the scene for the discussion of gene expression in Higher Human Biology Group work Communication skills Research skills IT skills Suggested solutions to focus questions 1. 2. 3. 4. 5. 6. Self-renew Specialised to perform a particular function through gene expression Pluripotent – can become many different types of cell Multipotent – can become different cells of the same type Repair and renew tissue Diseases where the tissue has degenerated and need replaced Pluripotent cells as they have a greater flexibility CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 5 ACTIVITY 1 Student’s notes In this activity we are going to explore the biology of stem cells further. Your teacher will go through the PowerPoint with you. At the end of the PowerPoint there are some focus questions for you to complete and a short research task. Introduction to stem cells What is a stem cell? A stem cell is a ‘master cell’ that is found in multicellular organisms. Stem cells are found in developing embryos and the adult organism , where they have slightly different roles to play. In both cases they are undifferentiated and have a unique property in that they can not only make new copies of themselves, but can also differentiate to become a specific cell type. Activity Can you give examples of differentiated cells and their functions? What is the difference between an embryonic and an adult stem cell? Embryonic stem cells The cells formed following the first few divisions of a fertilised egg are described as totipotent, which means they have the total capacity to become, or differentiate into, all the specialised cells of an organism plus the placenta. Figure 1 Stem cell cultivation. 1, in-vitro fertilised egg; 2, blastocyst stages (5–7 days old); 3, inner stem cell mass; 4, cultured undifferentiated stem cells; 5, specialised cells: (a) blood cells, (b) neural cells and (c) muscle cells. 6 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 1 Once the blastocyst stage has been reached (5–6 days after fertilisation) the cells have now become pluripotent, which means they can still differentiate into all the specialised cells of an organism, but not the placenta. Adult stem cells Figure 2 Adult stem cells. Illustration by the Cell Imaging Core of the Ce nter for Reproductive Sciences. The developed adult human also has stem cells in particular organs of the body (Figure 2). These are described as being multipotent. They are also undifferentiated but can only develop into a limited number of cell types that are closely related. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 7 ACTIVITY 1 Focus questions 1. What is the unique property of stem cells whi ch makes them different from specialised cells? 2. What does it mean when we say a cell has become differentiated? 3. Embryonic stem cells are described as pluripotent whereas adult stem cells are multipotent. Describe in your own words what these terms mean. 4. Why does adult tissue need stem cells? 5. Why are research scientists so interested in using stem cells? 6. We have discussed several types of stem cells. Which type would you think would be most useful to treat human disease? Give a reason for your answer. Group task Each group has to investigate a disease that could be treated with stem cells. For this disease: describe the condition identify the organ/system affected give a reason as to why stem cells rather than drug therapy would be beneficial. 8 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 2 Activity 2: An introduction to stem cell research and regulation Teacher’s notes Area of curriculum Higher Biology Unit 1 – 2 c i, ii Higher Human Biology Unit 1 – 1 a Aim The aim of this activity is to provide students with some ba sic information regarding how research using stem cells is carried out. Examples of their therapeutic use are dealt with in another activity and it is advised that this one is carried out first. This activity will take approximately 40 minutes. Students should be encouraged to read the material through and make notes of any questions they have as they are going through it. Knowledge and skills Encourage independent learning Obtain knowledge regarding health and safety and risk assessment regulations that companies producing therapeutic products have to adhere to Introduction to part of the process involved in human fertilised egg donation Introduction to a potential use of stem cells in blood production Numeracy and analysis Suggested solutions and discussion points 1. The regulatory bodies are the Human Tissue Authority and the Human Fertilisation and Embryo Authority. 2. GLP and GMP are necessary throughout to ensure there is traceability. If there is a problem following clinical use then traceability is obviously important. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 9 ACTIVITY 2 A useful website which contains related information can be found at: http://www.mhra.gov.uk/Howweregulate/Medicines/Medicinesregulator ynews/CON041337 It is not intended that this document is issued to students, it is merely to provide background information for teachers who do not have either GLP or GMP in their own background. 3. O type blood can be given to anyone and if it is stem cell derived then the SBTS is not totally reliant on donors. Also the blood will be contaminant free – no further screening is needed once it has been passed for clinical use. 4. Animal products may carry viruses that can be passed on if the stem cells are used for clinical use. Allergic reactions may also occur. 5. (a) (c) (d) (e) 10 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) 5 × 4 × 10 5 cells × 20cm 3 . Cytokines are needed for cell survival. Same cell number so that the two flasks could be compared . The two flasks have to be compared to observe the ce ll number with and without cytokine, ie flask 1 acts as a control. © Learning and Teaching Scotland 2011 ACTIVITY 2 Student’s notes Stem cell research is a very emotive subject which generates a lot of public debate and opinion. In this activity you will be introduced to some of the aspects involved in stem cell research and its regulation. You have some material to read through and a video clip to watch which will help you to answer the questions at the end. There is also a problem -solving activity in the last question that you will need graph paper for. What is involved in stem cell research? Before stem cells can be used to treat human disease we need to find out a lot more about them, just like the medicines we take for granted today , which have all gone through a research programme and have been considered to be safe. In order to study stem cells we need a supply of them. Any research group wanting to study stem cells, perhaps to develop a therapy from them, begins by creating a stem cell line. Cell lines are used routinely in research; they are a collection of cells that are derived from (come from) a parent group of cells. Stem cell lines are grown in culture dishes; they divide constantly and remain undifferentiated and pluripotent for many years. The example shown in Figure 3 is from a fertilised human egg created by IVF. The donors of this egg have gone through ‘informed consent’ to obtain their permission so that this egg can be used to harvest stem cells and derive a cell line from them. Figure 3 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 11 ACTIVITY 2 The stages involved in creating a stem cell line are shown below. Step 1 – Isolation. This could be from an embryo, as shown in the diagram above, or from an adult. Step 2 – Characterisation. The cells are tested for cell markers that let the scientist know they are indeed stem cells. A fraction of the cells are treated with drugs to make sure they have the potential to differentiate. Step 3 – Scale-up. To provide lots of cells for clinical studies. A Scottish company called Roslin Cells produces stem cell lines that are of clinical and therapeutic grade. Search for the following YouTube clip on Roslin Cells by searching for High Growth Award Winner 2010 – Roslin Cells within the YouTube site. Read through the questions first so that you are ready to take notes. 12 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 2 Questions 1. What are the two regulatory bodies in the UK that license work regarding stem cells? 2. The video stresses that the cells are produced to good manufacturing practice (GMP) and good laboratory practice (GLP). This is part of the quality assurance system that Roslin Cells operates within. Discuss with the class why you think this is important. 3. The video mentions a project that Roslin Cells are involved in with the Scottish Blood Transfusion service. The NHS requires 4000 litres of blood a day. The project is looking at the mass production of O -type blood using stem cells. Why is this blood type of particular interest? 4. At the moment many stem cell lines are grown in culture dishes surrounded by a fluid that provides nutrients. The nutrient solution contains products of animal origin. Suggest why Roslin Cells are trying to refine culture conditions so that they do not need these animal derived products. 5. A scientist is working on a stem cell line and is investigating the necessary growth conditions needed to make the stem cells differentiate into blood cells. The cultures were set up on day 0. The scienti st took the original flask of cells, counted the cell number and made sure each of the new flasks received the same cell number (as shown below). Original flask of cells Flask 1 with 4 × 10 5 cells per cm 3 Flask 2 with 4 × 10 5 cells per cm 3 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 13 ACTIVITY 2 (a) The scientist performed a five-fold dilution of the cells before transferring them into flasks 1 and 2. How many cells per cm 3 were in the original flask if the original flask contained 20 cm 3 of growth media? After 6 days of collecting results the scientist analysed the data , which is shown in the table below. (Note: Viable just means the cells that are alive.) Flask 1 – media only Day result collected Viable cell number × 10 5 per cm 3 Flask 2 – media + cytokine Viable cell number × 10 5 per cm 3 0 4.0 4.0 2 4.6 4.6 4 5.0 9.2 6 3.3 10.7 8 2.1 13.8 10 1.2 27.6 12 0.3 32.9 Use this data to plot the results of this experiment. 14 (b) What conclusion can you draw from these results? (c) Why did the scientist put the same cell number into flasks 1 and 2? (d) Why did the scientist need the two flasks a nd not just flask 2? CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 3 Activity 3: Therapeutic use of stem cells Teacher’s notes Area of curriculum Higher Biology Unit 1 – 2 c i, ii Higher Human Biology Unit 1 – 1 a Aim The aim of this activity is to allow students to explore stem cell therap ies already used in regenerative medicine through exemplification, and to consider the future of this area. This activity can be used in different ways. Examples of how the activity could be used are detailed below: Students could be divided into groups and each group could choose one of the therapies to study and answer the questions. Each group could then take it in turn to feed back to the rest of the class in a PowerPoint or scientific poster session. Each person in the group could be allocated a role such as reporter, note taker, researcher , etc. The class could go through one or more of the examples collectively . Each student could go through each of the examples independently. It is recommended that all students do the activity entitled ‘Therapeutic use – the future’. Knowledge and skills Deepen understanding of stem cell biology Broaden knowledge of physiology Depending on the approach presentation, communication and team working skills could be developed Independent learning Stem cell research regulation in the UK Consideration of ethical issues CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 15 ACTIVITY 3 Possible solutions to focus questions Therapeutic use – skin grafts 1. The patient has only to donate a small biopsy from which stem cells can be isolated and multiplied, as opposed to a larger section of skin. With a traditional skin graft patients have two areas which have to heal: the injury and the site of graft tissue. The stem cell technique suggests that scarring is also minimal. 2. If the biopsy is taken from an area close to that which is damaged the new skin will be of a similar thickness and pigmentation, which improves the appearance of the graft. Therapeutic use – bone marrow transplant 1. These stem cells can only differentiate into blood cells and not any other cell type. 2. The donor can replenish the stem cells because they self-renew. Therapeutic use – cornea repair Corneal transplant Advantages Can be used if both eyes are damaged. Disadvantages Not a permanent solution as the cells of the conjunctiva eventually invade. Relies on a suitable donor. Stem cell therapy Advantages Regenerative process with self-renewing epithelium. Uses individual’s own cells so there is no problem with rejection. Disadvantages Relies on the patient having one healthy eye. Therapeutic use – the future 1. Skin cells are easy to obtain. 2. In induced pluripotent stem cells (iPS) skin cells are converted back into pluripotent cells, then induced to differentiate into a different cell type. The new technique involves switching on the genes necessary to make it become a nerve cell, bypassing the pluripotent stage. 3. The cells signal to each other and behave physiologically like nerve cells. 4. iPS work is unlikely to be licensed as the cells can induce tumours. 5. Ethical discussion. 16 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 3 Student’s notes Therapeutic use – bone marrow transplants The following information describes a therapeutic application using stem cells. There are some questions at the end of the information to help you to develop deeper understanding of this therapy. Stem cell based therapies – bone marrow transplants Where do you find bone marrow? Bone marrow is the material found inside bones. It contains blood stem cells. Why might someone need a bone marrow transplant? An individual may have an inherited condition , such as aplastic anaemia, or they may have suffered a viral infection, such as hepatitis, or developed a type of cancer of white blood cells called leukaemia. In any of these conditions the bone marrow is destroyed and the body loses its ability to make new blood cells, fight infection, clot blood or transport oxygen/carbon dioxide. There are no drug treatments to cure these conditions and transplant of blood stem cells is the only option. Where do bone marrow stem cells come from to transplant? A person with the same genetic tissue type as t he person who needs the transplant has to be found. In 20–30% of cases this is most likely to be a brother or a sister. In the UK there is a British Bone Marrow Registry where people can register to become potential donors, and this can be searched for potential donors if a relative is not a suitable match. How are the cells collected? Directly from the bone of a donor during a surgical procedure. The donor can be given drugs to encourage the stem cells to move from the bone marrow to the blood. Filtering the donor’s blood removes the stem cells and the rest of the blood can be returned. Once a baby is born the umbilical cord blood can be filtered to isolate the stem cells, which are then genetically typed and frozen for future use. In 2009 the NHS Cord Blood Bank was established in the UK. What about the person needing the transplant? The patient has to undergo chemotherapy to destroy any of their own bone marrow, and then they receive a transfusion of the donated stem cells. These donated stem cells migrate to the bone and begin to grow – this is called cell engraftment. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 17 ACTIVITY 3 Focus questions 1. Explain why the stem cells described here could not be used for any other type of stem cell transplant, eg skin graft. 2. Stem cells have a unique property that means that even if some are taken from a donor, as described above, the donor is not harmed in any way. What is this unique property? 18 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 3 Therapeutic use – cornea repair The following information describes a therapeutic application using stem cells. There are some questions at the end of the information to help you to develop deeper understanding of this therapy. Stem cell based therapies – cornea repair The cornea covers the eyeball and is responsible for producing an image that is transmitted to the lens and then to the retina at the back of the eye. The cornea is covered with corneal epithelium (epithelia = the name of a cell type that lines or covers surfaces). For good vision the corneal epithelia needs to be intact and transparent. The corneal epithelium is connected to the conjunctiva (covers the white of the eye) by a small area called the limbus. The limbus has been shown to produce corneal epithelium stem cells. These stem cells ensure that if the corneal epithelium becomes damaged it can be replaced. The problem If the limbus in one eye is destroyed, perhaps by infection or as a result of a burn injury, the eye cannot make corneal epithelium s tem cells, so cannot repair the corneal epithelium. To protect the eye, the cells of the conjunctiva instead cover the cornea. The result is that the cornea becomes covered in blood vessels (because it is not the correct tissue) and eventually the individual loses their sight. Stem cell therapy Stem cells from the limbus of the patient ’s other (healthy) eye can be isolated and cultured in the laboratory. These cells can be transplanted into the damaged eye to repair the corneal epithelium and therefore recover the person’s sight. Interestingly, researchers discovered that if they screened the culture of stem cells for a particular ‘transcription factor’ (a specific type of protein) then they can tell how successful the transplant will be. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 19 ACTIVITY 3 Focus question The alternative to stem cell therapy is a corneal transplant through the organ donation scheme, where the patient’s damaged cornea is replaced. In this case the limbus remains damaged. Use the following table to list the advantages and disadvantages of each of the potential treatments for this condition. Corneal transplant Advantages 20 Disadvantages Stem cell therapy Advantages CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 Disadvantages ACTIVITY 3 Therapeutic use – skin grafts The following information describes a therapeutic application using stem cells. There are some questions at the end of the information to help you to develop deeper understanding of this therapy. Stem cell based therapies – skin grafts Did you know that the skin is the largest organ in the human body and makes up approximately 16% of total body weight? Figure 6 shows a cartoon of what a section of skin looks like under the microscope. The skin has several functions, including temperature regulation, sensation of touch and pressure as well as insulation. The epidermis is the outermost layer, which is renewed approximately every 2 weeks. The melanocytes provide pigmentation. Figure 4 The degree of epidermal thickness depends on the area of the body. For example, the epidermis is thicker on the soles of the feet compared to on the face. It has an additional function in providing a barrier to prevent the entry of pathogens (disease-causing agents, such as bacteria). The bottom layer of the epidermis is where the basal cells are found – these are the stem cells of the skin. Epidermal skin cells begin here and travel up through the epidermis to the outer layer. In cases where a person has either a second-degree burn to the skin or a large wound, or if the skin has become ulcerated, the epidermis is damaged and the delicate tissue of the dermis exposed. As the basal layer of the epidermis is no longer there , the skin cannot repair itself. In cases like these a skin graft is necessary. Traditionally, skin grafts involve the removal of skin from another area of the patient. This skin is used to graft over the damaged area. More recently, a new treatment has been developed using the patient’s basal cells. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 21 ACTIVITY 3 This procedure is summarised below: Skin biopsy taken from an area close to the site to be treated Sample treated with enzymes that isolate and loosen the basal cells Basal cells grown in culture to make a cell suspension that is sprayed over the damaged area The basal cells cover the damaged area and regenerate the skin. The quicker this process is carried out following injury the more effective it is. Focus questions 1. Suggest the benefits to the patient of this new procedure using stem cells compared to traditional skin grafting. 2. Why is it important that the skin biopsy is taken from an area close to the damaged area? 22 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 3 Therapeutic use – the future The information contained in this activity will let you find out more about the direction in which stem cell research is heading, and how it is regulated. It is also there to help you understand the newspaper article that ends this section. Once you have read the article you should answer the questions that follow it. What is the future of stem cell research? The examples of the therapeutic use of stem cells you have looked at so far are well-established procedures using adult stem cells. While these are successful techniques, their major drawback is the fact that adult stem cells offer little flexibility to treat other conditions. For example, although there are stem cells in the bone marrow they can only differentiate into blood cells because they are multipotent (can make different cells but only of the same type). New stem cell therapies for the future hope to offer a ‘stem cell repair kit’ that will enable injured, dead or degenerated cells, tissues or organs to be repaired or replaced. To do this we need to have stem cells that are pluripotent – that is they can differentiate into many different cel l types and not just, for example, blood cells. Where can we get pluripotent stem cells from? Embryos Cells found within a developing embryo are pluripotent. However, the use of human embryos in research brings up many ethical concerns. The laws in the UK give the early embryo rights, but they can be used in research that is tightly regulated and monitored. These surplus embryos are donated from patients undergoing in-vitro fertilisation treatment. Only embryos up to 2 weeks old can be used as the law prohibits work on embryos that are older than 14 days from the day of fertilisation. This is because at this stage a nervous system begins to develop. To work on human embryonic stem cells (hESCs) an organisation needs to have a license from the Human Fertilisation and Embryology Authority (HFEA), plus a license from the Human Tissue Authority (HTA). An HTA license is necessary because it is hoped that the research will eventually produce tissue that can be used to treat people. In the license application organisations have to show that hESCs are the only way that information about a serious human disease or its treatment can be obtained. If there are alternatives then a license will not be granted. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 23 ACTIVITY 3 Induced pluripotent stem cells Harvesting stem cells from an embryo destroys it. Research is now looking for an alternative to the pluripotent stem cells we get from embryos. This technique, which is called induced pluripotent stem cells (iPS), takes adult differentiated cells, like a skin cell, and reprogrammes them by switching off the genes that make it a skin cell. The reprogramming converts the adult cell to one that is in an embryonic-like state using genetic engineering. This produces cells that are like the pluripotent stem cells found in an embryo , but the cells are actually from an adult. Differentiated cell, eg skin cell Genetic engineering switches off genes that make it a skin cell iPS cell Muscle cell Nerve cell Other genes switched on that send the cell down another pathway of differentiation Liver cell This research has progressed even further, with a report published in 2010 describing the creation of nerve cells directly from skin cells, bypassing the iPS stage altogether. The following article reports on this study. There are questions after the article. 24 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 3 Neuron breakthrough offers hope on Alzheimer’s and Parkinson’s Source: The Times, 28 January 2010 by Hannah Devlin Neurons have been created directly from skin cells for the first time, in a remarkable study that suggests that our biological makeup is far more versatile than previously thought. If confirmed, the discovery that one tissue type can be genetically reprogrammed to become another could revolutionise treatments for conditions such as Parkinson’s disease and Alzheimer’s, opening up the possibility of turning a patient’s own skin cells into the neurons that they need. The study by scientists from Stanford University, California, also suggests that skin cells could be reprogrammed to provide a limitless supply of blood or bone marrow for personalised transfusions. Until now, the consensus was that only master cells from embryos, or adult cells that have been ‘rewound’ into an embryo-like state — a process that takes several weeks — have the ability to form all the different types of tissue in the body. The latest study, carried out in mice, reveals that while cells choose and maintain their speciality during the earliest phase of development, they retain an underlying flexibility. Provided that the correct genes are turned on or off they could potentially be turned into any other variety of tissue in the body. The work has been hailed as a huge conceptual leap forward in fundamental biology. ‘The possibility that cells could be directly reprogrammed is something that people had thought about, but to see it in black and white is still slightly shocking,’ said Professor Jack Price, a neurobiologist at King’s College London. ‘This suggests that there are no great rules — you can reprogramme anything into anything else.’ The finding will address some of the ethical objections of groups who oppose embryonic stem-cell research, in which the embryo is destroyed. And the new process is much quicker than the alternative method, where adult cells are ‘rewound’ to create versatile master cells, known as induced pluripotent stem (iPS) cells. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 25 ACTIVITY 3 In the study, published in the journal Nature, skin cells were infected with a genetically modified virus that inserted genes into the cells’ DNA. The researchers began by introducing 19 genes that are known to be switched on when mice stem cells first differentiate into neurons during embryonic development. Using a mix-and-match approach, the researchers found that of the 19 genes initially tested, only three were truly necessary to get the skin cells to develop into neurons. When these three genes were switched on, 20 per cent of the skin cells had turned into fully functioning neurons in less than a week. The neurons were able to make connections with and signal to other nerve cells — critical functions if the cells are eventually to be used as therapy for Parkinson’s disease or other disorders. ’We were very surprised by both the timing and the efficiency,’ said Irving Weissman, a stem cell expert at Stanford University in California, who led the research. ‘This is much more straightforward than going through iPS cells, and it’s likely to be a very viable alternative.’ In terms of clinical applications, a further advantage of skipping out the intermediate iPS state is that it is known that iPS cells promote cancers. Many researchers believe it would be difficult to obtain a license for the use of cells that are grown from iPS cells. ’People have been saying that iPS cells could be used therapeutically in the near future, but frankly they’ve been lying,’ said Professor Price. ’These cells don’t go through a tumourigenic phase, which means it would be much easier to get a licence to use them.’ The Stanford group are now working to reproduce the finding using human cells, but say that there is no reason to expect it should not apply to most species. A further question is why, if cells retain an underlying versatility, they don’t switch between cell types throughout our life. One possible explanation is that genes interact via ‘see-saw’ mechanisms, whereby when one set of genes are switched on, they automatically keep other genes switched off unless an artificial intervention is made. 26 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 3 Focus questions 1. Why do you think skin cells and not any other cell type were chosen as a starting material? 2. What is the main difference between the technique described here and that used to produce iPS? 3. How did the scientists know they had made nerve cells? 4. What is the main health concern if iPS are used to treat people? 5. Do you think the same ethics that govern hESCs should apply to these cells? CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 27 ACTIVITY 4 Activity 4: Roslin Cells video Teacher’s notes Area of curriculum Higher Biology Unit 1 – 2 c i, ii Higher Human Biology Unit 1 – 1 a Watch video at http://www.ltscotland.org.uk/video/h/video_tcm4664297.asp?strReferringCha nnel=highersciences&strReferringPageID=tcm:4 -654100-64 Aim The purpose of this activity is to introduce students to how stem cells for potential therapies are created and regulated, and the sorts of research the cells are used for. It is suggested that this video (which is 4 minutes long) is used as a prelude to Activity 5, so it could potentially be used as a piece of work the students do in their own time in preparation for Activity 5. Alternatively the activity can be used in class. Depending on the ability of the class, the following questions (some or all) can either be printed on paper for distribution for the students to answer as they watch the video or put on the board and used as discussion point s afterwards. There are no suggested timelines for this activity as it depends entirely on how the activity is used. Potential focus questions and answers 1. What type of cell was Dolly created from? Answer: Adult somatic cell 2. Human embryos are used to create human embryonic stem cell lines. Where do these human embryos come from? 28 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 4 Answer: They are donated by couples undergoing IVF. CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 29 ACTIVITY 4 3. What is the cut-off time by which embryos are either used or destroyed? Answer: Day 14. 4. What is the role of the quality control department at Roslin? Answer: They record patient information and number the embryo for traceability purposes. 5. Which authority regulates stem cell lines once they are cr eated? Answer: Human Tissue Authority. 6. What is the optimal stage in embryo development from which human stem cell lines are created? Answer: Blastocyst. 7. What are induced pluripotent stem cells (iPS)? Answer: Adult cells that behave like embryonic stem cells. 30 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 ACTIVITY 5 Activity 5: The great stem cell debate Teacher’s notes Aim This activity is designed to summarise many of the points that have been discussed in Activities 1–4, and gives students a chance to bring their own ideas and thoughts into the class. It must be stressed that there are no right or wrong answers here. Activity There are four characters, each representing people with an opinion on stem cell research. These characters could be used in a variety of ways: as a basis for an online discussion, for example via a blog or chat room to produce a newspaper article representing the viewpoints of the characters: groups of students could represent each of the characters, while others could interview them, and the article could be distributed within the class for discussion or distributed to other classes to gain a wider opinion as a basis for a debate where groups of students are involved in gathering and presenting the material for it as a basis for a more informal class discussion. Knowledge and skills Depending on the approach, presentation and IT skills could be developed Student-led activity that could help students gain confidence in expressing their opinions Independent research skills CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011 31 ACTIVITY 5 Characters Joseph Young ‘I am a 15-year-old who has been confined to a wheelchair since I was in a car accident several years ago. I can’t take care of myself and I rely on my parents to do most things for me – things that other teenagers take for granted. There is no drug or medicine I can take to cu re me, but I have heard that there are trials in America with scientists using human embryonic stem cells to repair the spinal cord of people just like me. I’d like to see the same sort of trials taking place in the UK. As far as the embryo is concerned, i t was a ball of cells that was going to be destroyed anyway – so why can’t the cells be used to help me?’ Rose Williams ‘I am a scientist who works in embryonic stem cell research. Donation of organs is now an accepted practice in this country, so why can ’t couples who have gone through IVF donate eggs that would eventually be destroyed if not used? There are many scientific reports coming out just now with iPS and similar, however, therapies using these cells are a long way off as they come with their own issues. At present embryonic stem cells offer the most promise to help those with incurable conditions and to relieve human suffering.’ Amelia Clark ‘My partner and I went through IVF in the hope we could have a child to love and care for. The other embryos that were created were more than we needed to use; they have the potential to be a brother or a sister to our child. It would feel wrong for me to allow scientists to use them for experiments.’ Josh Brown ‘I am a charity worker who campaigns tirelessl y for my charity. Research on human embryos is never going to gain public acceptance because there are too many ethical issues with it. The money that is given by the government to fund this research should be spread amongst other charities , which will help a lot more people in the long run.’ 32 CASE STUDY ON STEM CELLS (H, BIOLOGY/HUMAN BIOLOGY) © Learning and Teaching Scotland 2011