- Category: Science & Technology
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. PBS - NOVA Science - For a week, Dr. Leonard Zon answered viewer questions about stem cells. See his responses to the questions below:
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 using discarded umbilical cords during childbirth to derive stem cells. How is this different than stem cell research in the U.S.? Ashu Jaiswal, Minneapolis, Minnesota
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. Anonymous
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? Shirley Gossett, Chapin, South Carolina
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. Rodolfo Klebahn, San Antonio, Texas
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? Anonymous
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.
Anonymous
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....MORE...
