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Leonard Zon, M.D., is Director of the Stem Cell Research Program at Children's Hospital Boston, The Grousbeck Professor of Pediatrics at Harvard Medical School, and a Howard Hughes Medical Institute Investigator. Dr. Zon's laboratory uses the zebrafish as a model system for understanding blood development in all vertebrates, including humans. |
For a week in April 2005, Leonard Zon answered viewer questions about stem cells. See his responses to the questions below. Please note we are no longer accepting questions. Q: I watched the NOVA scienceNOW show but am not sure I understand how stem cells can actually help with studying the beginnings of disease. Or do I have this wrong and scientists are not considering that? Thanks. A: This is very important. Let's say I want to study Alzheimer's disease. Currently, the only way to study the disease is to look at autopsy samples of brains. In the brain cells, there are "tangles." These tangles clearly are important in the disease, but no one knows how they form and what would block them. It is possible to use a process called nuclear transfer to create embryonic stem cells from Alzheimer's patients. A skin cell from the patient would be removed and the nuclear material removed from that cell. The nucleus would be injected into a donor egg, and the egg is then activated by calcium. This causes cell division to start, and then cells are removed and placed in a tissue culture plate. Embryonic stem cells develop that carry all the mutations in the DNA that causes the Alzheimer's disease. Now, with embryonic stem cells available, it is possible to convert these to neurons. Perhaps we could then find the conditions that cause the tangles in the brain cells of Alzheimer's patients. Also, we could begin to look for chemicals that block the tangles from developing. This might be a new treatment for Alzheimer's disease. I believe that such Alzheimer's cells will be available over the next three years. This will really help doctors and scientists. Q: Scientists in India are going to be using discarded umbilical cords during childbirth to derive stem cells. How is this different than stem cell research in the U.S.? A: There are many researchers in the United States who study umbilical cord stem cells. Umbilical cords have many blood stem cells, and they are a source of "adult"-type stem cells. They can be used for transplants, particularly for treating cancer or leukemia. Q: Say scientists succeed in having human embryonic stem cells differentiate into insulin-producing cells, nerve cells, etc. How then would they use them to combat diseases such as diabetes, Parkinson's, etc. Do they inject them into a damaged area? What happens to the damaged cells—do they just stay there? Thanks for your time. A: That is correct. The cells must be transplanted. In some cases such as blood diseases or diabetes, the cells would be placed into circulation. The blood stem cells would travel to the bone marrow and amplify. The insulin-producing cells would be placed into a large blood vessel that leads to the liver. The protocol for islet cell transplants allows the cells to set up home in the liver and produce insulin. For neural stem cells, it would be necessary to place these into the brain. Q: Where are we in determining the use of stem cell transplants in lymphoma, diabetes, Alzheimers, and other debilitating conditions? A: We use adult stem cells to treat lymphoma and diabetes. For lymphoma, this involves bone marrow transplantation. Unfortunately, only one-third of patients have a matched donor so that the transplant can succeed. For the others, it might be possible to use nuclear transfer embryonic stem cells. This will take a while before they are available, because more science is necessary. It is critical to proceed with these experiments now. For diabetes, see answers elsewhere on this page. Q: Is there research being done towards the cure of autism with stem cells? My belief is that autism is caused by accumulation of mercury. A: I do not know of specific research in autism, although there is much research in nerve cell differentiation. Q: How can stem cell research repair demyelinating diseases like multiple sclerosis? A: There are several ways that stem cells can help multiple sclerosis. First, it may be possible to study the process of myelination in human cells. By studying the biology, more could be learned. Also, multiple sclerosis is caused by an abnormal response of the immune system. Stem cell research investigates aspects of the immune system that may help multiple sclerosis patients. Q: How can embryonic stem cells be made to differentiate, that is, be made to become blood cells or nerve cells or whatever? How do scientists go about doing that? Thanks for your time. A: Human embryonic stem cells are maintained in a certain culture condition, which keeps them in a primitive, that is, an undifferentiated state. Originally the cells were maintained on cells from mouse embryos, which provide nutrients and molecules that prevent differentiation of the human embryonic stem cells. The reason scientists used these so-called mouse feeder cells was that what exactly is beneficial to the support the human embryonic stem cells was not very well known. This has only been worked out recently and now scientists can grow human embryonic stem cells free of mouse feeder layer and thus avoid contamination by mouse molecules and pathogens. If one now wants to differentiate the human embryonic stem cells, all one has to do is to change the culture conditions by withdrawing the molecules that maintain the human embryonic stem cells in an undifferentiated state, and add in some other molecules, depending on what cell type one wants to obtain. And the cells then "obey" the cues given by these new molecules and differentiate into the wanted cell type. These molecules will be different for differentiating blood cells than for nerve cells, for example. While this sounds very easy and is now quite routinely practiced for blood cells, nerve cells, and other cell types, it took many years of trial and error to get there. Fortunately, much was already known through over 20 years of research with mouse embryonic stem cells, so in some instances it just was enough to adapt the protocols to human cells. Although it is important that these cells look like blood cells, it is also important that they function properly in the body. For this, everything has to be in place within the cell: the surface molecules to respond to the body environment and to get where the cell needs to integrate into the tissue; the molecules linking the outside signals to the inner signals of the cell; the molecules that transport those signals to the nucleus and make sure that the right genes are expressed in the right amount at the right time, and so on. For example, insulin-producing cells have to respond to very precise signals in the body to produce the right amount of insulin exactly when needed. Not more, not less, and not sooner and not later. An added challenge is to produce enough cells (it would take many more cells for curing humans than a tiny mouse), and at high purity, as one cannot inject residual, undifferentiated embryonic stem cells, as these would make tumors. And this is why although scientists now know how to make many cells of the body from human embryonic stem cells in culture, clinical applications are still many years away. Q: My name is Tahnee Day and I am 19 years old. I was diagnosed with type I diabetes two days before my 18th birthday. My GP concluded that my diabetes came around five months prior when I was sick with pneumonia and strep at the same time, and the virus eventually made it to my pancreas. I have only had diabetes for a short time. Does this mean that I have a better chance of being cured if stem cell research is successful? Diabetes does not run in my family. Though my Grandpa had type II, I know it is not hereditary unless it is the same type. Or does the fact that I am diabetic from an illness rather than it being hereditary make me unable to be cured? Or does it make the research more difficult? Before being diagnosed, I was healthy, athletic, and ate balanced meals. I still do. I just wanted you to know that I wasn't obese. Thank you very much for your time. I hope and pray that you are successful in your research. Good luck! Sincerely, A: Dear Tahnee, Thank you for your question. It is important to realize that you are not alone, and many people have Type 1 diabetes. In fact, your story is a common situation to discover that someone has diabetes. There is a link to viral infections and diabetes, but the interaction between the virus and the immune system that causes diabetes is not known. Strep is a bacteria and has not been associated directly to cause diabetes. Since you have only had diabetes for a short time, the immune destruction of the pancreas may not have happened completely. Some patients, in fact, have a short period of time when their insulin requirement gets better, called the honeymoon period. We currently do not have embryonic stem cell therapy for diabetes, but if we did, it would be an advantage to treat sooner than later. You should continue to monitor your diet and frequently check blood sugars. You may consider an insulin pump. We will continue our research that may help you some day. Q: It's Jackie Bernstein Weisman, from Muhlenberg! I teach 7th grade science in Marple Newtown. We have two questions: If you were cloned, would the new person have the same personality as you? If a child was born with a disability (chromosomal abnormality) and stem cells were taken when they were born, would it be possible to make them develop normally? Thanks! A: Dear Jackie and class, It is great to hear from you. I went to college with you, and also I'm a graduate of Paxon Hollow Middle School, and Marple Newtown. I still remember the school colors are black and gold. Even worse, I still remember the school song. I played soccer, ran track, and also played in the band there. Now I'm a Professor at Harvard. It would be very unlikely that the personality would be identical. It was thought for many years that personality may be due to genes (that is nature), but much of it is environment and education (that is nurture). A clone of a person would resemble that person at least as much as an identical twin brought up in a different family. For question 2, it would depend on what the genetic defect was. For example, kids with a certain form of immune deficiency, the so-called bubble kids, can be cured with blood stem cell transplants. But this is for a disease with a mutation in one single gene. If an entire chromosome or parts of a chromosome are affected, it is not possible to correct this with current technology. One would have to somehow swap the damaged chromosome with a healthy one. This would be difficult. One important area of research is to make embryonic stem cells from Down's children, who have an extra chromosome. These cells will be very helpful to understand the multiple problems of organ development and function in Down's children. I would hope that this would lead to a better understanding of chromosome problems, and could lead to some new therapies for such patients. Q: With cloning, after you replace the DNA of a woman's egg with someone else's DNA and you put the egg back into the woman, does that egg have to be fertilized to create a human? A: Dear Gary, No, fertilization is when the sperm (with one half of the chromosomes) and the egg (providing the other half of the chromosomes) fuse and make a zygote, which now contains a full set of chromosomes. The zygote then very quickly starts dividing and developing into an embryo. In the case of nuclear transfer, the DNA from the other person is already a full set of chromosomes. But as no sperm has entered the egg and has triggered the fusion process, the egg doesn't know that it now has a full set of chromosomes. So scientists have to coax the egg to divide and develop, by chemical or electrical stimulation. But whether that would result in the birth of a human is not certain, as in animal cloning the numbers are staggeringly low. On average, not even 5 percent of nuclear transfer eggs make it to birth. And even those are highly abnormal and have many major health problems. Which is why scientists agree that human reproductive cloning should be banned. Which currently is NOT the case in the U.S. One is just not allowed to do it with federal dollars. Q: How far along are other countries in using stem cells to create cures for diseases such as Parkinson's? A: Currently several groups in the U.S. (4), in Korea (2), and in Japan (1) struggle with deriving good dopamine-producing neurons from human embryonic stem cells. While progress is promising, and the cells look like real dopamine-producing neurons in culture, it is still a challenge (for all of them) to make them perform properly in animal models. Q: What would be lost in the process of stem cell creation by restricting the research to "adult" stem cells or cord blood stem cells? In other words, what's the downside of these areas of research rather than "full blown" embryonic stem cell research? A: Dear Alden, As a scientist I have to answer that both adult and embryonic stem cells have to be studied extensively and in parallel, as both have something to teach us, and there are specific advantages for each stem cell type. Whether human embryonic stem cells or adult stem cells are used in future therapies will probably depend on the type of disease or injury. Thanks to the ease of growing them in the laboratory, human embryonic stem cells may one day become the source of artificial organs. Or, scientists might one day be able to mobilize one's own adult stem cells to repair tissue damage caused by trauma, disease, and even aging. But as adult stem cells don't grow well in culture, experimentation is very difficult and slow. Moreover, except for bone marrow and cord blood, it is difficult to obtain human tissue in sufficient quantities to extract meaningful numbers of adult stem cells. So progress is faster in the embryonic stem cell field. As a comparison, human embryonic stem cells were only first derived in 1998. Blood stem cells and mesenchymal stem cells (the two better characterized adult stem cells, both in the bone marrow) have been known for 100 years, and blood stem cells have only been routinely used to cure leukemia and blood disorders over the past 20 to 30 years, and mesenchymal stem cells have only been explored in clinical trials in the past one to two years. But the complementary information acquired from studying both stem cell types is key to unlocking their full potential. Q: I have heard conflicting reports as to whether stem cell trantsplants have ever been successful in humans. I thought they have been. A: Dear Kathy, The majority of stem cell clinical trials now underway use blood stem cells from the bone marrow or umbilical cord blood to treat blood disorders or diseases, such as leukemia, different types of anemia, systemic lupus, and certain other autoimmune diseases or deficiencies. In addition, a handful of clinical trials are evaluating the use of one's own bone marrow stem cells to repair heart tissue and to improve blood flow or to help to repair bone and cartilage. Other adult stem cells being explored for use in the clinic include stem cells in the eye and the skin. For several years tissue transplants have been performed. For example, insulin-producing cells for Type I diabetes, fetal neurons for Parkinson's disease, and skin for bladder reconstruction have been transplanted successfully. It is possible that in cases where long-term regeneration has been achieved, stem cells contained in these tissues have contributed to regeneration. No clinical trial has yet used therapeutic cells derived from human embryonic stem cells. But then, human embryonic stem cells were only first derived in 1998, whereas blood stem cells and mesenchymal stem cells have been known for 100 years. On the other hand, diseases such as myocardial infarction, severe immune deficiency, diabetes, Parkinson's disease, spinal cord injury, and demyelination have been successfully treated in mice with mouse embryonic stem cells, providing proof-of-principle that embryonic stem cells can be used. Now it just needs to be worked out in the human setting. Q: Hello, While the debate on whether allowing stem cells to be used for medical purposes rages on, I the diabetic need a better monitor. We need a monitor that does just that -- monitor. It would be inserted under the skin being constantly bathed in blood constantly monitoring blood and transmitting the results to a receiver worn on one's wrist like a wristwatch. A diabetic should always know what his blood sugar is without having to poke a hole in our bodies. A monitor like this could communicate with an insulin pump and regulate insulin as a pancreas would only artificially. I think that one day you will perfect stem cell use and it will one day be considered the norm, but until then use the technology that we have today for people that have the need today. It's like NASA sending a probe to Mars that takes seven years to get there, that technology is seven years outdated upon arrival. Thanks for your time. A: Dear Paul, Thank you for your comment. Monitoring blood sugar has become a major industry. You are talking about continuous monitoring. This is a great idea, and many companies are trying to do this. Medtronic's MiniMed device provides up to 288 glucose measurements every 24 hours. Please contact your physician. You should maybe contact your local university's bioengineering program; they may also be interested in developing such a device. But in the meantime, we will continue our work on stem cells. Q: At what point in the process of cleavage are embryonic stem cells isolated? A: Great question. The most common time to remove the cells is the blastocyst stage. This is usually at about six days of development. But the time varies by a few days depending on the laboratory. Q: What are the differences between stem cells in an embryo and stem cells in an umbilical cord? A: This is a frequent question that I receive. Umbilical cord stem cells are usually already committed to the blood system. They are the equivalent of blood stem cells from adults, but are actually of fetal origin. Some investigators have also cultured "mesenchymal" cells from umbilical cords, and these can be used to make connective tissues. The terminology is poor, but umbilical cord stem cells are "adult"-type stem cells. That is why I would rather call them "tissue" stem cells rather than adult stem cells. Embryonic stem cells are derived from embryos during the blastocyst stage. They can become any tissue. Q: If stem cell researchers had all the money in the world, and their work didn't become illegal (as some politicians in this country would like to make it), how soon would you expect effective treatments using stem cells to combat serious diseases to be available? Where would you expect the field to be 25 years from now under such circumstances? Thank you for your time. A: There is still a lot of basic science that needs to be done before embryonic stem cell research can translate into the clinic. It is very important that scientists and doctors do not overpromise that therapies are just around the corner. My expectations are that it will take us about 10 years to determine how to make embryonic stem cells into tissues that can function in the body. We will also have to establish protocols to do this in the clinic, and this takes a lot of time. Some tissues such as blood and pancreas can be transplanted through protocols that already exist, but transplantation protocols for other tissues may need to be perfected. It may take 15 years before the protocols are routinely used as therapy. It is critical for the science to move forward right now. Any delay will extend this timetable. Q: I watched the NOVA segment about embryonic stem cell research and was struck by the scientist's perspective on personhood. It seems to me to be a bit convoluted to say that someone else's personhood is defined by one's attachment to him or her. Perhaps he did not express himself well, but to use his reasoning, he would have to allow that some people apparently do have extremely strong attachment to embryos in general. Considering that to these people using fertilized human eggs for research and experimentation is as abominable as cannibalism may be to the scientists who do stem cell research, how can one expect them to tolerate the idea that their tax dollars are to be used to fund this? Since almost no one has an objection to adult stem cell research, would it not make more sense to direct government money toward that? A: The important part about this discussion is that all opinions are respected. We believe that both adult and embryonic stem cell research must be pursued. Adult stem cell research has been helped significantly by understanding development, including through embryonic stem cell research. The goal is to develop the technology to ultimately treat a variety of diseases. Q: My husband was diagnosed with Type 1.5 diabetes five years ago, and we have been strong supporters of embryonic stem cell research. Do you have recommendations of what steps we can take to ensure this issue gains more importance in the national spotlight? Also, do you know if there might be a grassroots effort in our area where we might volunteer our time and expertise? A: Thank you for your comments. There are a number of organizations that support embryonic stem cell research. I suggest that you enter the public page of the International Society for Stem Cell Research Web page (http://www.isscr.org). This is a group of scientists and doctors who are the braintrust of the world doing stem cell research. Most importantly, please call your state representatives and congressmen to discuss your views on stem cell research. Q: I don't understand why feeder cells are not needed. How is it possible to create embryonic stem cells (ESCs) that can produce their own nutrition and hormones, and is it possible to turn ESCs into autotrophs? A: Interesting question. Many cell lines for tissues cannot grow on their own. This includes ES cells. The feeder layers produce growth factors and matrix factors that allow good growth and maintain health of the cells. If you remove the feeder layers, the cells will die. In the mouse ES cells, there is a growth factor called LIF that prevents differentiation. This allows the cells to be grown without feeders. However, this LIF does not work in human ES cells. Most ES lines from humans have been made on mouse feeder layers. The mouse feeders can produce factors that trigger an immune response, and may be a source of mouse viruses. To get around this, human feeders would be better. More research is necessary to come up with the LIF equivalent. Recently, some researchers have described interesting conditions that may accomplish the block in differentiation. As with many cell lines, one may be able to find a line that feeds itself growth factors, but this might not be helpful when looking at how tissues differentiate. Q: Doctor, I am a Type 1 diabetic, which happened when I was 59!? No one in my family has or had this disease. I have heard about islet transplants and watched your video about stem cell cloned transplants. How do these differ? And which one is more likely to be effective in growing new islet cells for Type 1's? Thanks so much for answering. A: Currently, the only treatment that is available is the islet cell transplants. We have not yet figured out how to make human embryonic stem cells into insulin-producing cells that could correct your disease. It is important to realize that the islets come from cadavers, and there are not enough islets to help all the Type I diabetics in the country. We need to have a limitless supply of insulin-producing cells. Since ES cells could potentially become islets, this is one of the most active areas of research. Many scientists are working hard on this problem, and I believe the problem will be solved. You will likely have to wait for years until the protocols are ready for the clinic, so I do not want you to think that such transplants will happen soon. But the good science that is being done will help in the long run. Q: Why are people afraid of cloning human beings when a person is more than a mass of cells and is also made up of his or her experiences? A: The word "cloning" is a poor term. It seems to evoke responses. A cloned animal resembles the donor, but there are many differences likely due to experiences, etc. |
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