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Stem Cells Under the Microscope: A Stem Cell Primer by Thomas Robey  Thomas Robey The stem cell debate is a topic Americans are increasingly familiar with. The 2004 and 2006 elections brought stem cell research into the nation's political consciousness, and along with climate change and evolution, stem cell science will provide one of the few overtly scientific topics in the 2008 debates. Nearly everyone knows of a friend or family member with an affliction curable or potentially cured by stem cell therapies. Almost as familiar is the notion that certain kinds of stem cells are collected from human embryonic tissue. In fact, stem cell research is controversial among Christians for the same reason that contraception, in vitro fertilization and abortion generate rancor in public discussions. The hinge is the question, when does human life begin? Scientists and theologians both agree that science cannot offer a definitive answer. (This Christian stem cell scientist's attempt to wrestle with personhood in the context of embryonic stem cell research will be the topic of a future column.) The intention for this article is to provide a primer to stem cells; with it the reader will be better prepared to evaluate the latest stem cell reports from the media. The stem cell debate's roots are intertwined with religion and politics, but the language is very technical, and as the philosopher of biology Jane Maienschein argues, the language really matters (1). When you encounter any study or affiliated political statement that extols the virtues of a particular type of stem cell, there are three parts to one question you should ask yourself before writing home to the folks about it. That question is: What kind of cell is it? 1. Was the cell an embryonic or adult stem cell? 2. Did the experiments use human or mouse cells? 3. What were the measurements of this cell's potential, and what do they mean? Most readers leave this last question to the author scientist, but the flavor of these reports range from conservative skepticism to unbridled enthusiasm. Unlike in evolution or climate studies, there is no overwhelming agreement among stem cell scientists about different cells' properties or potentials. Stem cell science is still arrayed in camps and factions. Identifying answers to the questions above will prepare you to make a rational evaluation of the claims made by researchers, reporters and politicians. What Kind of Cell?  A stem cell under the microscope The first question you should ask is whether the research used adult or embryonic stem cells. If the answer is 'embryonic,' you should figure out which cell line was used. What is a stem cell line? Embryonic stem (ES) cells are derived from a hollow ball of one hundred cells called a blastocyst. In the human, the blastocyst forms after fertilization but before implantation into the uterus, so is referred to as a pre-implantation embryo. When you hear of the embryos frozen at in vitro fertilization (IVF) clinics, it's these five-day-old blastocysts they're talking about. The blastocyst has two components: the shell that eventually forms the placenta, and the inner cell mass, which develops into the fetus. Delicate techniques enable scientists to remove these inner cells and coax them into growing on a plate. Grown under certain conditions, these cells will renew themselves indefinitely. If cells taken from a blastocyst reach this point, they are called a cell line. Cells taken from ES cell lines have been guided down pathways to nearly every cell type in the body, so are pluripotent. Pluripotency is the distinguishing characteristic of embryonic stem cells, and is the reason scientists are so excited about them. No other cell has the ability to form every cell type in the body. Certain cell lines ("federally approved" means they were made before August 9, 2001) are eligible for federal money, but no law governs work with non-approved lines; scientists just can't spend taxpayer money on it. Private companies or university endowments finance research using lines produced after that date. The first mouse ES cell lines were created in 1981, but human lines weren't made until 1998. The seventeen-year gap is the reason it is important to know whether a new discovery occurred in mouse or human cells. For reasons that are not fully understood, human ES cells are very different from their mouse counterparts. A breakthrough in the mouse does not imply imminent success in the human. If the answer to "What kind of cell?" is 'adult,' you will need to ask a few more questions. There are more than 20 major classes of adult stem cells, and every month, revelation of a new type hits the media. Most adult stem cells serve a simple purpose: to renew and repair the tissue in which they are found. Some of these resident stem cells can lead to just one tissue, while others may differentiate in to several; this property is called multipotency. The blood, skin and gut have rapidly dividing stem cells, muscle cells divide less frequently, and it is still very controversial whether nerves and heart have stem cells that divide to a lesser extent. Despite promising reports in the 1990's, it is clear that adult stem cells very rarely trans-differentiate - that is, a blood stem cells do not turn into heart stem cells. This does not preclude the possibility that adult stem cells could someday be reprogrammed to do so, such as the recent case of a skin stem cell being pushed to a less differentiated progenitor that is ES cell-like. The irony is that this technology borrows heavily from knowledge gained from ES cell research! A second major type of stem cells resides in the bone marrow and are called mesenchymal stem cells. These cells are less differentiated and have been shown to form more types of cells than resident stem cells. They have many of the same protein markers on their outer surface as embryonic stem cells, and scientists have been able to definitively lead these cells down paths to become bone, cartilage, muscle and fat. Claims have been made that they form nerve, heart, blood, liver and pancreas cells, but this is where it is important to answer the third question: How was 'potential' measured? A tricky characteristic of mesenchymal stem cells is that they tend to fuse with other cells, thereby acquiring their partner's characteristics. The result is a case where the cell looks like a duck, and quacks like a duck, but wouldn't have a clue what to do if it were put in water. The true test of whether a stem cell is pluripotent is if it forms many different cells, which in addition to displaying correct surface markers, appropriately conduct electrical signals, contract like muscle, secrete insulin, and so on. Shown these things, you can be confident that the cells can swim like a duck. Three other classes of adult stem cells bear mentioning. Cord blood stem cells are isolated from the umbilical cord and placenta after birth. These stem cells are a kind of super blood stem cell. This somewhat diverse population of stem cells can be coaxed into all blood lineages and most mesenchymal cell types. For this reason, and because everyone has an umbilical cord, several companies offer to store cord blood in the event that future disease requires a stem cell-based treatment. Fetal stem cells are classified as adult stem cells because they are not pluripotent. These cells should not be confused with ES cells. They are collected from the tissue of aborted fetuses, and were used in human clinical trials to treat Parkinson's disease in the late 1990's to modest success, but the technique has not been pursued to a significant extent. A discovery recently in the news was of a stem cell found in amniotic fluid. This cell is very similar in behavior to fetal stem cells and displays many of the characteristics of mesenchymal stem cells, so much so that skeptics suggest that these are simply cells shed off of the fetus as it grows in the womb. There will likely be additional exciting discoveries of currently unknown adult stem cell types, but before holding them up as proof that ES cell research is unneeded, we must consider whether the new cells actually have the same properties of ES cells. History of Hype and Hope Senator Sam Brownback (R-KS) and other political opponents to embryonic stem cell research have claimed that 69 different human illnesses are being treated by adult or cord blood stem cells (2,3). This number is a blatant misrepresentation. In fact, only nine of the conditions on this list are treatable with adult stem cells (4). The most common stem cell therapy is bone marrow transplant, which was first used in 1968 to treat immune deficiency, a disease of the blood, and can now treat some blood cancers and diseases. Forty years of human adult stem cell research were preceded by several decades of study in animals, and we see today the benefit of this investment. Thousands of people a year, including many children, receive cures for deadly diseases. On the other hand, human embryonic stem cell research is approaching its tenth year. No treatment has been approved, but many have been hypothesized. (Emphasis on the hype.) It is still too early to tell how many, if any therapies will come from embryonic stem cell-derived cell transplants. No one knows if transplanted embryonic stem cells will be rejected like in organ transplants. The problem of tumor formation is real but not insurmountable; some of the same chemicals that lead ES cells to form specialized tissues also prevent them from forming cancerous overgrowths. Even in this short time, human ES cell research is already teaching us about early human development and about cancer. New ES cell based techniques are providing ways for complex diseases previously only known to exist in patients to be studied in a Petri dish. And most notably, techniques applied to control the developmental pathways in ES cells are being tested on adult stem cells. In this way, embryonic stem cell research's legacy may be as a bridge to new adult stem cell therapies. Notes 1. Jane Maienschein. The Language Really Matters in The Stem Cell Controversy, 2nd edition. M. Ruse and C.A. Pynes eds.; p 37-53. Amherst, NY; Prometheus Books. 2006 2. David Prentice, Christianity Today, 49 (no. 10), p 71 (17 Oct 2005). 3. Sam Brownback, Stem Cells, Congressional Record, Senate p S4005-S4006. (4 May 2006). 4. Shane Smith, William Neaves, and Steve Teitelbaum. Adult Stem Cell Treatments for Diseases? Science, 313, p 439 (28 July 2006). Thomas Robey is an MD/PhD student who studies both adult and embryonic stem cells at the University of Washington. Past issues - Print edition - Media Kit - About Christian Faith and Reason ©2007 Christian Faith and Reason
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