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Feature Article Stem Cell Research and Health Education David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg ABSTRACT Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new mil- lennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the embryonic form. Consequently, there is public confusion over the benefi ts currently being derived from the use of stem cells and what can potentially be expected from their use in the future. The health educator’s role is to give an unbiased account of the current state of stem cell research. This paper provides the groundwork by discussing the types of cells currently identifi ed, their potential use, and some of the political and ethical pitfalls resulting from such use. INTRODUCTION become cells with specialized functions.2-6 “regenerative medicine.” Under “normal” Stem cells are believed to be one of These cells replicate to generate “offspring” conditions stem cells continue to replicate the greatest untapped resources currently cells that can be either stem cells (and hence, until they receive a signal to differentiate available for the prevention and treatment self-renewing) or specialized cells (i.e., dif- into a specifi c cell type.8 When stem cells of many diseases. Inasmuch as current ferentiated cells) that play a specifi c role— receive such a signal they fi rst become pro- knowledge of stem cells is a combination becoming blood, bone, brain, or skin cells, genitor cells, and later, the fi nal mature cell of scientifi c reality and cautious specula- among others.7 Stem cells, therefore, have the type. Determination of the different signals tion, considerable research is required to potential to act as repair systems for replace- that cause the stem cell to become a specifi c identify the true, long-term potential for ment of damaged cells.2-6 The fi eld in which type rather than just continue to replicate medical advances from these cells. As health a great deal of research is currently underway is important (and, in some cases, it is the resources professionals, communicators, and to determine the use of stems cells in the absence rather than the presence of a signal advocates,1 health educators are in a position treatment of diseases and injuries is called that is the important factor).8 The ability of to advance the public dialogue about this promising technology. This article offers a general overview of stem cells, their potential David Eve is an instructor at the Center of Excel- [email protected] and rmcdermo@health. for extending life and improving its overall lence for Aging and Brain Repair, Department usf.edu. Stephen K. Klasko is vice president of quality, and some thoughts on the role of of Neurosurgery, University of South Florida USF Health and dean of the College of Medi- health educators with regard to professional College of Medicine, 12901 Bruce B. Downs Blvd. cine at the University of South Florida; E-mail: and lay audiences. (MDC 078), Tampa, FL 33612; E-mail: deve@ [email protected]. Paul R. Sanberg is a health.usf.edu. Phillip J. Marty and Robert J. distinguished university professor and director WHAT ARE STEM CELLS? McDermott are professors in the Department of the Center of Excellence for Aging and Brain Stem cells are template cells found of Community and Family Health, University of Repair at the University of South Florida; E- throughout the body that can grow to South Florida College of Public Health; E-mail: mail: [email protected]. American Journal of Health Education — May/June 2008, Volume 39, No. 3 167 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 116677 44//3300//0088 66::2266::5588 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg stem cells from one area to differentiate into (described later in this article). Existing stem differentiating or changing in any detectable another completely different type is known cells for medical research can come from way. They can either be frozen for storage as plasticity, and embryonic stem cells ap- four primary sources: existing stem cell lines, or continue replicating. However, there is pear to be the “most plastic” of the four types aborted or miscarried fetuses, discarded some evidence that with continued passag- discussed below.2-6 embryos from fertilization treatments, or ing, a point may be reached in which the Stem cells are described as being of a cloned embryos. Only the fi rst source can be cells become less stable with respect to their specifi c cell line, dependent on the charac- used in federally funded research programs, ability to replicate, differentiate, or avoid teristics and location of the original template however.11,12 mutations.21 This instability seems to be cells from which all future offspring cells The cloning of embryos is another particularly true when adult and embryonic have grown (refl ecting the self-renewing controversial area of research. The cloning stem cells are compared (see below). capability of the cells). Assuming that no of humans to full term is banned almost Fetal stem cells, typically obtained fol- contamination of the cell line occurs as a worldwide.13,14 In some cases, short-term lowing abortion or miscarriage, are believed result of mutations or infections, and no cloning has been performed to allow for to be as pluripotent as their embryonic differentiating triggers occur, the cell lines the generation and extraction of stem cells, counterparts, though they occur at a later could potentially grow ad infi nitum.2 followed by the termination of the cloned stage than the true embryonic stem cell.22 embryo by the sixth day after fertilization. Several biotechnological companies are DIFFERENT TYPES OF STEM CELLS Cloning of some animals has been allowed experimenting with these cells as treat- There are several types of stem cells: em- to proceed to full term; the fi rst and most ments for a myriad of diseases. For instance, bryonic stem cells, fetal stem cells, adult stem famous example was the work of Scottish ReNeuron, Inc. (UK) has several cell lines cells, embryonic germ cells, and amniotic scientists resulting in the creation of a sheep derived from the fetal brain that they are and umbilical cord stem cells. These stem known as “Dolly.”15 That achievement be- testing for the treatment of neurodegenera- cell varieties and their distinct properties came the driving force for new regulations tive disorders, including stroke, Parkinson’s are discussed below. to prevent a similar event occurring with disease, and Alzheimer’s disease.23,24 Embryonic and Fetal Stem Cells human cells. The latest evidence suggests Adult Stem Cells The development of an organism can be that cloned cells do not “reset their longevity A small number of stem cells can be compartmentalized into several stages.9 Fol- clocks,” thus resulting in reduced lifespan. found in adult humans at specific loca- lowing the union of the egg and sperm, the Furthermore, not only is the success rate tions, such as in the bone marrow or the initial four to fi ve days from conception are of cloning low, but the cloned organism is subventricular zone of the brain.25,26 Until characterized by a period of rapid cell divi- beset with problems, some of which may not the discovery of these and other cells in the sion. A “ball” of 50 to 150 cells known as a become apparent until adulthood, assuming central nervous system, it was believed that blastocyst is created, so named because it is a life extends to that age.16,17 the brain was the only organ that could hollow sphere. The blastocyst is composed of For research to occur with embryonic not replicate. However, it is now clear that three parts: the trophoblast or outer surface, stem cells, the inner cell mass of the blasto- certain regions of the brain may have some the blastocoel or inner cavity, and the inner cyst is extracted (thus destroying the embryo) limited capability to replace damaged or cell mass found inside the blastocoel which and grown in cell culture.18,19 This process dead cells as a consequence of endogenous is composed of stem cells.9 These inner-lying enables cells to grow on plates coated with stem cells.27,28 cells are said to be “embryonic” even though a feeder layer that provides anchorage and Whereas embryonic stem cells are the term embryo does not technically apply nutrients. The stem cells become attached to derived from the inner cell mass of the until after this initial two-week stage. the plate and grow in the nutrient broth (i.e., blastocyst, knowledge of the origin of the The next eight-week stage is character- cell culture media tailored to the specifi c adult stem cell is less certain. Its source ized by cell growth and multiplication. Fol- needs of the cell line being grown).18,19 As could potentially be the same, with the adult lowing this eight-week stage, the organism the cells proliferate they fi ll the plate until stem cell being many generations removed has recognizable structures and is classifi ed a point is reached where they would be from the original source. If this speculation as a fetus. At this time, embryonic stem cells forced to compete for space and nutrients. is true, then one would expect the body to continue to proliferate and are said to be Shortly before such competition breaks out, have large numbers of these cells, which it pluripotent or plastic, meaning that they can the cultures are replated at the original cell does not. It has therefore been suggested that differentiate into almost any type of cell that density (meaning that one starting plate halting of replication is the means by which makes up the body.10 The embryonic stem could be divided across two or more plates) the number of stem cells found in the organs cell is believed by many scientists to be the and the process is repeated. This procedure is of the body is limited.29 The stem cells are most useful for potential medical treatments, known as “passaging.”20After several months, said to have entered a state of quiescence, but its use is restricted by federal legislation the cells will number in the billions without until they receive an activation signal due 168 American Journal of Health Education — May/June 2008, Volume 39, No. 3 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 116688 44//3300//0088 66::2266::5588 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg to cell damage. Determination of the signal might be for use in treating human disease that it has been found to contain stem cells, that triggers adult stem cells to “wake up” and injury. there is potential for further research and is critical to maximizing their benefi t. In Most research on adult stem cells is based storage of such fl uid. The current belief is addition, identifi cation of what makes the on mesenchymal cells, i.e., cells from regions that amniotic fl uid contains a mixture of cells quiescent is of considerable merit. One originally derived from the mesodermal embryonic and adult stem cells.47,48 Testing study revealed the presence of a “master layer of the embryo. These cells include of these cells has been limited to date. It is be- switch” that can trigger the change from connective tissue and, in particular, bone lieved that they are able to differentiate into embryonic to adult stem cell characteristics, marrow and muscles. They are multipotent a variety of cell types, but it is not known suggesting that this signal may originate cells and are a relatively homogeneous popu- whether they are as pluripotent as other from the same source.30 lation of mononuclear progenitor cells that types of stem cells. Some authorities have There is considerable debate as to how can be made to differentiate into specifi c suggested they could be used as a potential pluripotent adult stem cells are. The original cell lines following environmental cues. Ad- treatment for diabetes.49 belief was that they were not as versatile, ditionally, there are stromal stem cells found Umbilical cord blood contains low healthy, or durable as embryonic stem cells in the bone marrow, which are a more het- levels of stem cells as well as a number of because they appeared to be limited to form- erogeneous population of different cell types hematopoietic (blood forming) cells, includ- ing only cells of a similar origin (e.g., bone with varying degrees of proliferation and ing lymphocytes and monocytes. There is a marrow stem cells could only produce blood differentiation potential.40 Adult stem cells considerable amount of research focusing cells). Consequently, these cells became also can be found in children, in the placenta, on umbilical cord blood for the treatment known as multipotent cells. These charac- and in blood from the umbilical cord. These of stroke, myocardial infarction, and a va- teristics meant that adult stem cells would be specialized cells are discussed below. riety of blood-related disorders, with some harder to manipulate or control compared Embryonic Germ Cells degree of success.50-53 The benefi ts of such with embryonic cells. Also, due to their pres- Germ cells are the precursors to the gam- blood have already been demonstrated in ence in adults, it is likely that the cells could etes (egg and sperm) and are therefore found the treatment of hematopoietic disorders, have accumulated abnormalities through in adult testes and ovaries, and in the areas of with over 6,000 transplants being performed continuous exposure of the organism to the embryo that ultimately differentiate into worldwide since it was fi rst used to treat a environmental hazards (such as viruses) or testes or ovaries.41 These cells appear to be as fi ve-year-old child affl icted with Fanconi to replication errors.31,32 The latter problems pluripotent as other embryonic stem cells. anemia in 1988.50 And there is good experi- are normally corrected, but with the aging However, they have been found to differenti- mental evidence that it can help with other organism, the ability to correct replication ate spontaneously, which would suggest that disorders as well.53,54 However, it is unclear errors is believed to diminish.32,33 In the there is less control over their development precisely how these benefi ts are obtained. majority of cases, the ability of adult stem than with other stem cells.42 Current evidence suggests that in many cases cells to replicate also appears to be limited Two studies43,44 suggest that adult stem it is not the stem cells per se that provide compared with embryonic stem cells, thus cells can be easily derived from germ cells the benefi t, but rather the growth factors reducing their usefulness.34 However, these of both sexes. Further research is needed these cells release. Some research shows that cells do have an advantage over embryonic to explore the validity of this hypothesis, umbilical cord blood cells do seem to have stem cells: theoretically, they can be removed though the fi ndings are certainly intriguing the ability to become neuronal-like cells in from a patient, grown in culture, and then and potentially useful. vitro, but do not appear to produce neurons returned to the patient.35 Therefore, they Amniotic Fluid (or Placental) and Um- of any signifi cant number in animal models would not induce an immunological rejec- bilical Cord Blood Stem Cells of stroke.53,54 tion response that may be seen with embry- The amniotic fl uid that surrounds and The current research interest in umbili- onic stem cells.35,36 In addition, there is more protects a developing fetus in its mother’s cal cord blood cells53,54 has resulted in the fl exibility in using these cells than human uterus, as well as the placenta, have also been formation of many companies worldwide embryonic stem cells, especially with regard shown to contain stem cells.45 An amnio- that allow public and private storage of these to federal funding. centesis procedure—where amniotic fl uid cells. As a result, at least 18 states have pro- Some research shows that certain adult is collected through the insertion of a long, posed legislation to encourage and inform stem cells can differentiate into a number of thin needle into a pregnant woman’s abdo- the public about this potential resource, varied cell types, including neurons37-39 of men to check for abnormalities, including and in several cases to provide funding for the peripheral and central nervous system. Down syndrome—is generally considered the setting up and/or running of umbilical However, this observation may not be true safe for both the mother and embryo.46 cord cell banks (see http://www.ncsl.org/ of all adult stem cells, and more research is The collected amniotic fl uid is normally programs/health/genetics/geneticsDB.cfm required to determine how useful these cells discarded once testing is complete, but now for a searchable database of such legislation). American Journal of Health Education — May/June 2008, Volume 39, No. 3 169 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 116699 44//3300//0088 66::2266::5588 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg Additionally, offi cial Japanese, European, were revoked in April 2007 by the U.S. Patent of Cardiology’s Innovation in Intervention, and Australian banks exist, as well as the and Trademark Offi ce,65 but WARF appealed March 25, 2007). Also, Yacoub75 announced many private companies that are currently the decision. In March 2008, WARF’s appeal that his team has been able to grow a heart “getting in on the act.”55-57 This resource was upheld.66 To provide cells to researchers, valve from bone marrow stem cells using could prove to be valuable. Although the the National Institutes of Health has estab- a collagen scaffold. This procedure has potential benefi t of these cells still remains lished a subsidy that allows the purchase of yet to be tested to determine if the valve is relatively unexplored, the practice of bank- cell lines approved in August 2001, at much functional in vivo, but it clearly represents a ing them already has at least one undeniable reduced rates, thus resolving some of the promising discovery. Similarly, preliminary benefi t: providing donors with a source of previous issues related to their use. testing of the recently discovered stem cells their own cells, which considerably reduces Many of the adult stem cell trials are also in amniotic fl uid for treating heart disease the chance of rejection if they ever do need oncology studies rather than regenerative has demonstrated some encouraging results them for medical reasons. medicine studies.67,68 Ongoing clinical stud- that require further study and verifi cation.76 Two other recent papers have demon- ies include phase II trials in which patients Unfortunately, transplantation of these cells strated an additional potential source of suffering from myocardial ischemia have has been accompanied by a strong immuno- adult multipotent stem cells: menstrual their own adult bone marrow stem cells logical response. blood.58,59 transplanted into their heart, theoretically Elsewhere, a study using embryonic stem increasing revascularization of the affected cells has shown considerable improvement POTENTIAL USES OF STEM CELLS areas.69,70 Additional cardiac therapies are in mice specially bred to exhibit symptoms Adult stem cells derived from bone summarized in a review by Ramos and of Sandhoff disease, a childhood disorder.77 marrow (i.e., the hematopoietic system) Hare.71 The implanted cells appear to function by have been used frequently over the past 30 A myriad of basic research is underway replacing the neurons killed by the disease, years for successful treatment of numerous worldwide on both embryonic and non- as well as restoring normal levels of the en- blood-based disorders. Current treatments embryonic stem cells derived from a number zyme hexosaminidase (low levels cause the include nuclear radiation exposure and of sources. This research encompasses treat- disease). The disease was found to eventually transplantation for the treatment of genetic ment of various disorders including organ return, but Lee et al.78 believe that additional diseases or cell cancers of the blood and the regeneration, cardiovascular improvements, treatments could inhibit recurrence and are blood-forming system.40,60-63 diabetes, and neurodegenerative conditions. conducting further research in this area. According to a White House report, there They comprise the complete continuum of Preliminary fi ndings from other studies are currently more than 1,200 non-embry- research from preliminary explorative stud- involving fetal neural stem cells in culture and onic stem cell clinical trials under way, while ies through preclinical and clinical trails. in animals have shown rescue of retinal cells none are being performed using embryonic Promising results include the promotion after injury or disease.79 This observation ap- cells.64 The freeze on federal funding to sup- of liver regeneration by bone marrow stem pears to demonstrate a restorative rather than port embryonic studies, rather than a lack of cells in patients with hepatic malignan- a replacement action by these cells. effi cacy, is most likely a major factor behind cies,72 the formation of blood vessels in In general, considerable research is this statistic. It is important to remember, mice from human embryonic stem cells underway to ensure that the development however, that embryonic stem cell research that have been made to differentiate into of treatments involves only those cell types has never been illegal in the United States; it endothelial precursor cells,73 the treatment being sought, and that it includes ways of just cannot be funded from federal sources of stroke and heart ischemia animal models ensuring desired outcomes—i.e., control- other than those lines that were approved by human umbilical cord blood transplants ling the stem cells so that they form the in August 2001. It is also noteworthy that in rats,51,53,54 and the ability of embryonic desired cells and do not proliferate indefi - adult stem cells have been researched for stem cells to differentiate into functioning nitely, which could lead to malignancy once three decades, whereas embryonic stem heart tissue (myocytes).74 Adult stem cells transplanted. Achieving such outcomes may cell research is considerably more recent, also have been used for the latter purpose, constitute one of the biggest stumbling with the fi rst human embryonic stem cell but the differentiated cells appear to impair blocks to stem cell research. One possible being isolated in 1998 at the University of heart function. However, preliminary data method would be to differentiate the cells Wisconsin–Madison by James Thomson.18 from a clinical phase I trial of an intrave- before transplantation; Keller79 has sum- That discovery led to several patents/li- nous formulation (Provacel) of adult bone marized various attempts at this method. censes by the Wisconsin Alumni Research marrow–derived mesenchymal stem cells Yet, a study involving transplantation of Foundation (WARF), further restricting appears to demonstrate some benefi t in de- stem cells obtained from the human central the use and research of such cells, given the creasing subsequent problems among heart nervous system into a primate Parkinsonian expense of purchasing them. These patents attack patients (Schaer, American College model resulted in behavioral improvements 170 American Journal of Health Education — May/June 2008, Volume 39, No. 3 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117700 44//3300//0088 66::2266::5588 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg and integration of cells without tumor benefi t may be more related to controlling most signifi cant involves moral arguments formation.80 Therefore, predifferentiation the infl ammatory response that causes cell regarding the use of embryonic material to of cells before transplant may not be neces- death or to promoting more rapid healing. harvest stem cells. The focus of this contro- sary, though further research is required A study by Capone et al.86 demonstrated that versy is on when life begins—which some to be sure that this is the case. This avenue stem cells do act in this fashion, modifying consider to be at conception—and whether of research is likely to see many initiatives, the microenvironment following stroke to any individual has the right to terminate a given the anticipated dividends. afford neuroprotection, rather than replac- life. Strong spiritual and religious beliefs are Additionally, study of the body’s ability ing “sick” cells. Similar fi ndings have been frequently central to this controversy, and to reject “foreign” tissue is also important observed in other studies, including the eye the practice is considered unacceptable by because certain embryonic tissue is likely to experiments mentioned previously. Thus, many. One study97 suggested the possibility have the ability to induce a signifi cant im- stem cells may help to support the cells that of removing one or a few stem cells without munologic response. Some studies are now are already present and protect them from harming an in vitro–fertilized embryo prior suggesting that immature embryonic stem further injury or death due to the factors to implantation, thus maintaining its viabil- cells and umbilical cord blood cells are not that cause or perpetuate the initial disease or ity. As of yet, however, it is unclear exactly as likely to cause an immunological reaction injury. This support in turn leads to another what impact this action has on the growing as differentiated adult stem cells.81-83 With consideration: are pluripotent cells necessar- organism and whether such studies can be adult stem cells, harvesting from the same ily better than multipotent ones? Assuming confi rmed. Consequently, because of the patient undergoing the transplant generally that adult stem cells from a specifi c source controversy over when life begins, many eliminates this problem. (e.g., adult stem cells from the brain) can dif- countries either ban embryonic stem cell A few studies have found that co-trans- ferentiate into the required replacement cell research or severely restrict it. As indicated plantation of two or more different types of (e.g., neural cells) or provide the required previously, only those embryonic stem cell cells has resulted in a synergistic effect that supporting factors, they do not need to be lines approved for study in August 2001 can maintained their survival and execution of pluripotent. Therefore, pluripotent (em- receive federal funding and support in the benefi cial effects. For instance, the co-culture bryonic stem) cells would only be required United States. of amniotic epithelial and neural stem cells when adult stem cells are not present or Three connected groups of scientists promoted neuronal differentiation of the cannot differentiate into the cell of inter- reported success in transforming normal latter.84 Both trophic support and direct con- est or produce the necessary factors to give mouse skin cells into embryonic stem tact between the two cell types appeared to the desired result. Consequently, research cell–like cells via genetic manipulation.98-100 have important but independent effects on on both pluripotent and multipotent cells Further research is required to confi rm these the neuronal survival and differentiation. would seem to still be necessary.87 fi ndings and those of other studies101,102 have One caveat to consider in stem cell treat- Not only does stem cell research provide translated this technique to human cells. ment of disease is that the replacement of direct cell replacement benefi ts or improve Additionally, the transformed cells are prone dying cells by new ones is only a temporary the survivability of “sick” or “injured” to tumorigenesis, and therefore, would not solution because whatever resulted in the cells, it also offers considerable insight be useful for transplantation in humans in death of the cells initially—unless purely on what causes cells to proliferate and their current form. This technique would intrinsic to the dying cells themselves or only differentiate—an important phenomenon not necessarily replace the use of embryo- a onetime event—will eventually prove le- to understand in the fi ght against cancers derived stem cells, as further characteriza- thal to the new cells, too. This phenomenon and in general research dedicated to the de- tion is necessary to confi rm that the cells has been demonstrated in a paper on fetal velopment and normal life cycle of cells.88-92 do possess all of the same characteristics— tissue grafts for the treatment of Parkinson’s Studies of stem cells could, therefore, have including the same receptors and response disease.85 Consequently, calling stem cells far-reaching implications that are not lim- to treatments. Nevertheless, it is a small step a “cure” for diseases is really a misnomer; ited to just disease treatment.88-94 Finally, in the right direction for those opposed to instead, calling them the “best available stem cells could also be used to model or- embryonic sources. treatment” may be more accurate at present. gans for the testing of drugs or new surgical A second controversy surrounding stem This caveat makes the assumption that stem techniques—another potentially powerful cell research is the apparent groundbreaking cell transplants are replacing the dying cells. benefi t of stem cell research.95,96 outcome of studies performed by a research Studies on stroke models using umbilical team in South Korea. In 2004, this team cord blood–derived stem cells do not sup- PREDOMINANT CONTROVERSIES reported in Science that they had obtained port the idea of replacement, but do show an ABOUT STEM CELL RESEARCH human embryonic stem cells from the improvement in the size of the stroke lesion There are four main controversies cur- nuclear transfer of oocytes (i.e., the replace- and behavioral markers.53,54 Some of their rently surrounding stem cells. Perhaps the ment of the nucleus of an egg with that of American Journal of Health Education — May/June 2008, Volume 39, No. 3 171 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117711 44//3300//0088 66::2266::5599 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg an already differentiated cell). The following tested in stem cells, perhaps creating the abil- of Yamanaka101 and Thomson102 may make year, this team again reported in Science that ity to turn off the malignant characteristics this controversy a moot point. Expanding they were able to generate patient-specifi c of these cells. on the mouse studies98-100 mentioned in an immune-matched embryonic stem cells for At the same time, another recent study earlier section, they reported two similar the treatment of diseases. In the end, the data suggested that although stem cells—specif- methods of converting adult human skin were found to be fraudulent, and some of ically, those obtained from bone marrow— cells into embryonic-like stem cells. This was the female researchers had apparently been may look like malignant cells, they do not achieved by the insertion of 4 genes that led coerced to donate their own eggs for the necessarily function like them. In other to the reprogramming of the cells (interest- process of obtaining stem cells, a signifi cant words, stem cells may not be cancerous and ingly, two of the genes differed between the ethical breach in the fi eld.103 As a result of may not be able to seed tumors.106 Further research groups but had similar functions). these fi ndings, both papers were retracted in research is required to determine whether This research has great potential but requires 2005, and signifi cant penalties were imposed this is true for all stem cells found in tumors, considerable additional testing to ensure that on the researchers. This scandal cast a large and whether they are acting as “developmen- the embryonic-like stem cells behave in a shadow over the competitiveness in the fi eld tal mimics” or seed tumors. similar fashion to embryonic stem cells ob- and the possible unethical means of obtain- The fourth main controversy concerns tained in the “normal” fashion. Additionally, ing stem cells for research purposes. whether adult stem cells are as benefi cial there is the concern that one of the genes the A third controversy has to do with stem as embryonic stem cells. A seminal paper researchers inserted was a cancer gene, which cells’ alleged potential to produce malignan- from a group led by Catherine Verfaillie (see could increase the likelihood for tumorigen- cies once implanted due to their theoretically Jiang et al.107) reported that adult stem cells esis using this approach. There is also concern immortal nature (viewed as such because from the bone marrow of rats, which they over the retroviruses used to insert the genes, stem cells can reproduce ad infinitum). called “multipotent adult progenitor cells” which can have potentially carcinogenic and Some research suggests that certain kinds (MAPCs), had the potential to differentiate other detrimental effects due to their ability of stem cells could cause cancer because a into almost every type of cell in the body, a to randomly insert the gene of interest into small number of defective stem cells have claim that previously applied only to embry- the genome. A major bonus of this approach been found in tumors, where they may onic stem cells. Unfortunately, little success is the ability to take the cells from the patients have acted as a seed.104 Given their ability to has been made in replicating these results. themselves and therefore reduce the likeli- proliferate continuously, these cells carry an More recent evidence suggests that the paper hood of transplant rejection. There is also increased likelihood of mutations, which in was fl awed, adding further consternation to the potential to model a disease more directly turn increases the probability that they will this area of investigation.108,109 Subsequent by removing the affected cells from a patient grow out of control and become cancerous. research from a number of teams reported and growing them in culture so that they can Therefore, their use in treatments could that when MAPCs could be successfully be characterized and compared with healthy be fraught with problems, at least until a isolated from bone marrow using a differ- cells. Research by Jaenisch’s group117 has clearer understanding emerges regarding ent technique than that originally proposed, demonstrated that reprogrammed skin cells the signals that turn them on and off in their they did have the ability to become any type can treat the sickle cell anemia mouse model, growth cycles. Adult stem cells are normally of blood cell but not other cells. But overall, thus confi rming the potentially benefi cial ef- quiescent, meaning that identifi cation of the it is still unclear whether this and other fects of such cells. process by which mutations occur could types of adult stem cells are as effi cacious prove to be vitally important in preventing as originally proposed.110-112 Criteria that STATUS OF LEGISLATION ON STEM transplant tumorigenicity or in preventing stem cells have to meet to be classifi ed as CELL USE cancers altogether. pluripotent have been proposed,113,114 and In the United States, federal funding for Interestingly, studies using embryonic few studies have actually met these criteria, embryonic stem cell research from sources carcinoma cells—which are malignant, with the majority being explained by cell such as the National Institutes of Health is similar to stem cells, and generally derived fusion115 and incorrect interpretation.111,116 restricted by congressional legislation, which from germinal cells—have provided some Thus, many researchers still believe that mandates that only cell lines approved in Au- neurodegenerative improvement in animal embryonic stem cells may provide more gust 2001 be used in funded research. At that models.105 These cells can be made to differ- benefi t due to their hypothetical ability to time, there were more than 60 lines, but only entiate into human neurons under retinoic differentiate into all cell types, though most 20 have proven to be viable and available acid treatment. When this conversion oc- would prefer both avenues to be explored, for general use. All of these cell lines have curs, the cells appear to lose their malignant acknowledging that adult stem cells could been grown on a mouse fi broblast feeder properties.105 Once the mechanism for this be useful in some circumstances. layer to restrict differentiation and only al- process has been determined, it could be Two independent studies by the groups low replication. Unfortunately, it has been 172 American Journal of Health Education — May/June 2008, Volume 39, No. 3 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117722 44//3300//0088 66::2266::5599 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg found that these stem cells are likely con- state level is California, which proposed its exceeding any that the National Institutes of taminated with mouse proteins and sugars own legislation in 2004 (Proposition 71) Health would likely provide. This alternative that could generate severe immunological involving the sale of $3 billion in bonds to funding source has also piqued the interest responses following transplantation into provide $295 million annually for 10 years of pharmaceutical companies. Such compa- humans to treat diseases.118 However, some to the funding of stem cell research.124 nies may be able to position themselves for studies suggest that the proteins and sugars Since then, several other states have a larger share of patents and licenses from can be removed or cultured out to make sought endorsement of similar propositions state-funded research—they already have a the cells safer for human transplantation.119 (Tables 1 and 2). Currently, at least 33 states near monopoly on drug therapies derived Newer procedures that use completely hu- have specifi c guidelines with respect to the from this research. This apparent paradox man components have been developed, so use of embryos in research, which in several was discussed in an opinion piece in The any future cell lines are unlikely to have cases (e.g., Arizona, South Dakota, Texas) Scientist by Dr. Paul Sanberg.126 this problem. Research involving adult conform to federal legislation. However, stem cells is not limited under the current there is considerable variation among these STEM CELL RESEARCH AND HEALTH federal restrictions. states regarding their support of separate EDUCATION PRACTICE The 20 embryonic cell lines that are feder- initiatives for stem cell research. Health educators are charged with ally permissible represent only a small frac- The International Society for Stem Cell numerous roles and responsibilities in the tion of the genetically and immunologically Research recently proposed international public sector.1 These essential tasks inter- heterogenous population of the world.120,121 guidelines for the use of embryonic tissue to sect with current and anticipated research This limitation casts doubt over whether any ensure uniform research and experimental involving stem cells. What follows is an treatments derived from these cell lines will practice worldwide.125 At the core of these iteration of ways in which health educators be suitable for treating all of the ethnically guidelines is that embryonic research should might be expected to address relevant stem diverse populations that exist in the United be rigorously overseen by sponsoring orga- cell knowledge and research issues. Although States and abroad. This limitation is both nizations or regulatory bodies with specifi c not exhaustive, the points below highlight an incentive for developing additional cell policies and procedures that conform to the the importance of keeping public dialogue lines and an important factor that should be recommendations of the scientifi c com- about this topic both vibrant and accurate. considered with respect to all types of stem munity. In all policies, no cloning is to be Assessing Individual cells. The genetic diversity inherent in the undertaken to create humans. The society’s and Community Needs world’s different ethnic groups implies that policies also recommend the establishment Health education competencies and different ethnicities may respond in different of an institutional oversight committee to subcompetencies in this area include, but are ways to these cell lines. Therefore, any suc- review and determine approval of all stem not limited to, selecting valid sources of in- cess found with these cells would need to be cell research. The use of “chimeras” (i.e., formation about health needs and interests. replicated using cell lines derived from other animals created with human cells) is al- The debate over stem cell research inevitably ethnic groups to determine their general use lowed with approval from this committee. becomes enmeshed in moral arguments and among the world’s population.122 Further, the use of any cells donated for political posturing, so it is important that In 2006, a congressional bill was proposed research purposes should require consent scientifi cally accurate information and data to allow research on stem cells derived from from those donating them. Regulations be made prominent in the public eye. Health embryos discarded after in vitro fertilization pertaining to stem cell use by state and educators are positioned to translate techni- treatments. This bill was vetoed by the presi- country are kept reasonably up to date at cal information and make it accessible to the dent based on ethical, moral, and religious the following websites: lay public and other interested consumers. concerns. The bill resurfaced following the • http://www.ncsl.org/programs/health/ Presently, although there are many avenues 2006 midterm elections in which Democrats genetics/embfet.htm of availability for this information in the regained control of the House and Senate, • http://isscr.org/public/regions scientifi c and medical communities, it is far but no change to the veto is likely under the less available to the general public. What is current administration.123 Initially, the federal funding restriction needed are accurate sources of relevant stem The restriction on federal funding for was seen as detrimental to stem cell research. cell data and other information that neither embryonic stem cell research led New Jersey However, some scientists are now suggest- refute scientifi c discovery nor escalate opti- to appropriate state funding for research on ing that the restriction has actually opened mism inappropriately or prematurely. both embryonic and adult stem cells in early other funding opportunities that may be 2004. Ohio had previously proposed funding more helpful to the research community. Planning, Implementing, and dedicated to adult stem cell research. The As Table 1 shows, federal restrictions have Administering Strategies and Programs most well known example of funding at the created unprecedented state funding far The highly diverse nature of the health in- American Journal of Health Education — May/June 2008, Volume 39, No. 3 173 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117733 44//3300//0088 66::2266::5599 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg Table 1. States That Are Encouraging Stem Cell Research State Year Legislation Status Funding Issuance of bonds to raise money for funding stem cell $3 billion+ over 10 California 2004 Passed research years $100 million over 10 Connecticut 2005 Fund for stem cell research Passed years Recommendation of state money for non-embryonic stem cell Florida 2007 Pending $20 million research (another bill proposed to provide for embryonic) Study and recommendation commissioned by state for the Hawaii 2006 University of Hawaii to investigate “the feasibility of encour- Pending N/A aging stem cell research” Illinois 2006 Illinois Regenerative Medicine Institute Passed $15 million Research on fetal stem cells derived from placentas, cord Indiana 2005 blood, amniotic fl uid, or fetal tissue allowed; adult stem cell Passed $50,000 research center at Indiana University Plan to establish Center for Regenerative Medicine; allows Iowa 2007 Pending N/A embryonic stem cell research Maryland 2006 Maryland Stem Cell Research Fund (not oocytes) Passed $15 million (2007) (cid:127) Institute for Stem Cell Research and Regenerative Medicine Passed $1 million Massachusetts 2005 at University of Massachusetts (cid:127) Life Sciences Investment Fund (including stem cell research) Passed $10 million Currently bans embryo and fetal research; several propos- Minnesota 2007 als to support stem cell research using other types (and also Pending N/A embryo) (cid:127) New Jersey Stem Cell Institute 2004 $23 million New Jersey (cid:127) Issuance of bonds for funding several stem cell–related Passed 2006 $270 million research facilities in state (ballot-rejected proposal in 2007) Proposal to fund the building of a stem cell research facility, including embryonic research; current legislation prohibits $10 million over New Mexico 2007 Pending research on live fetus/embryo, but use of fertility treatment three years excess permitted $300 million over two years 2006 (cid:127) New York State Institute for Stem Cell Research and Regen- New York erative Medicine Passed $100 million in 2007 (cid:127) The Empire State Stem Cell Trust” created for all stem cells 2007–2008 plus $500 million in 2008–2017 Adult stem cell research only; Center for Stem Cell and Re- $19.4 million plus Ohio 2003 Passed generative Medicine $8 million in 2006 Bill to allow stem cell research under institutional research South Carolina 2007 Pending N/A board approval Virginia 2006 Fund to support adult stem cell research Passed N/A Life Sciences Discovery Fund; may include funding for stem Washington 2006 Pending N/A cell research Wisconsin 2006 Funding for Stem Cell Products Inc. Passed $1 million Sources: Compiled from various online reports, including www.ncsl.org/programs/health/genetics/embfet.htm, http://isscr.org/public/regions, and “Yahoo! Alerts Health News: Stem Cells” (all last accessed December 7, 2007). 174 American Journal of Health Education — May/June 2008, Volume 39, No. 3 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117744 44//3300//0088 66::2266::5599 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg Table 2. States with Legislation Relating to Embryonic Stem Cell Use State Legislation Arkansas Research prohibited except on stillborn fetuses Louisiana Prohibits research on embryos Research prohibited on in vitro–fertilized embryos; a bill has been proposed for stem cell research this Maine year Michigan Dead embryos and fetuses available for experimentation by consent Missouri Prohibits research on live fetus Montana Prohibits live fetal research Nebraska Restricted use of money for embryonic stem cell research; a ban on cloning proposed New Hampshire Prohibits maintenance of unfrozen fertilized embryo beyond 14 days North Dakota Research (after consent) on embryos from sources other than abortion Oklahoma Prohibits research on fetus and embryos Pennsylvania Prohibits research on live fetus and embryos Prohibits research on in vitro–fertilized embryos post implantation, but pending legislation for embry- Rhode Island onic stem cell research with the consent of both parties involved in the creation of the embryo South Dakota Prohibits destruction of embryos Tennessee Allows research on aborted fetuses, but requires consent Utah Prohibits research on aborted fetus or post-implanted embryo Sources: Compiled from various online reports, including www.ncsl.org/programs/health/genetics/embfet.htm, http://isscr.org/public/regions, and “Yahoo! Alerts Health News: Stem Cells” (all last accessed December 7, 2007). formation consumer includes different levels a spiraling fashion on past activities. Stem various computerized health information of health literacy, disparate ethical and moral cell research is a pioneering endeavor, and resources, access those resources, and em- belief systems, and widely varying learning the knowledge shifts can, therefore, be rapid; ploy electronic technology for retrieving styles. Health educators are professionally the need for recurring data and information references. To enhance the match between prepared as a group to respond to the needs sources suitable for general and specific information and audience, health educators of these different audiences by identifying audience consumption is as dynamic as the should be positioned to perform readability individuals and groups who can best benefi t shifting sands. Health educators are prime assessments using such tools as the SMOG from knowledge about stem cell research, candidates for interpreting these changes, Test,127 the Flesch Reading Ease Formula,128 incorporating appropriate organizational putting them in context, and making the and other indices,129 thereby increasing the frameworks, establishing specifi c learning necessary and relevant adjustments to the likelihood that relevant information about objectives based on assessment of baseline public’s informational needs. stem cells will be understood. knowledge, assigning audience-specific Serving as an Education Resource Person Advocating for Education about Stem modes of education delivery, and develop- Health educators should be masters at re- Cell Research ing a program delivery method that includes trieval of information that can be translated Health educators are expected to analyze optimal use of learning technologies. from technical to more audience-friendly and respond to current and future needs in Health educators are able to assess both language. As with their other resource health education. Particularly pertinent to knowledge and attitude shifts through the functions, health educators should be able stem cell research is the analysis of factors use of well chosen surveys and other as- to match information needs with the ap- (e.g., social, demographic, political) that sessment instruments. Moreover, health propriate retrieval systems; to select data and infl uence individuals who make decisions educators can infer needed future activities data systems commensurate with program about the direction of, and restrictions and programs that build either in a linear or needs; and to determine the relevance of on, stem cell research. Currently, the wise American Journal of Health Education — May/June 2008, Volume 39, No. 3 175 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117755 44//3300//0088 66::2277::0000 PPMM PPrroocceessss BBllaacckk David J. Eve, Phillip J. Marty, Robert J. McDermott, Stephen K. Klasko, and Paul R. Sanberg course may be for health educators to be as for Stem Cell Research. United States, 2006. human: two national commission reports against politically neutral as possible in organizing Available at: http://stemcells.nih.gov/info/ human cloning from Italy and the U.S.A. HEC and communicating information about scireport/2006report.htm. Accessed October Forum. 2006;18(2):156-171. stem cell research—standing neither for 28, 2007. 15. Wilmut I, Schnieke AE, McWhir J, et al. Vi- nor against liberalization of current re- 3. Alliance for Stem Cell Research. Key facts able offspring derived from fetal and adult mam- search postures by the federal government about stem cell research. United States, 2006. malian cells. Nature. 1997;385(6619):810-813. and other entities. Health educators, like Available at: http://www.curesforcalifornia.com/ 16. Campbell KH, Alberio R, Choi I, et al. any other professional group, are subject to page.php?id=4 Accessed October 28, 2007. Cloning: eight years after Dolly. Reprod Domest their own biases, including those emanating 4. Nature Reports. What are stem cells? United Anim. 2005;40(4):256-268. from personal moral philosophy, ethical Kingdom, 2007. Available at: http://www.nature. 17. Check E. Cloning special—Dolly: a principles, or other convictions. Neverthe- com/stemcells/2007/0706/070614/full/stem- hard act to follow. Nature. 2006;445:802 less, they are obligated to report on stem cells.2007.12.html. Accessed October 28, 2007. 18. Thomson JA, Itskovitz-Eldor J, Sha- cell matters factually. They can also serve 5. International Society for Stem Cell Re- piro SS, et al. Embryonic stem cell lines as advocates for promoting discussions in search. FAQ. United States, 2005. Available at: derived from human blastocysts. Science. the public sector, at professional confer- http://www.isscr.org/public/faq.htm. Accessed 1998;282(5391):1145-1147. ences, and in their own scientifi c literature. October 28, 2007. 19. Hovatta O. Derivation of human em- Finally, practice standards support health 6. National Research Council. Understand- bryonic stem cell lines, towards clinical quality. educators’ participation in continuing ing Stem Cells: An Overview of the Science and Reprod Fertil Dev. 2006;18:823-828. education on stem cell issues and their Issues from the National Academies. Washington, 20. Masters JR, Stacey GN. Changing me- development of plans for ongoing profes- DC; National Academies Press: 2006. Available dium and passaging cell lines. Nature Protocols. sional development. at: http://dels.nas.edu/dels/rpt_briefs/Under- 2007;2:2276-2284. standing_Stem_Cells.pdf. Accessed October 21. Draper JS, Smith K, Gokhale P, et al. CONCLUSION 28, 2007. Recurrent gain of chromosomes 17q and 12 Stem cell research is a major area in 7. Morrison SJ, Kimble J. Asymmetric and in cultured human embryonic stem cells. Nat biomedical research, one that could have symmetric stem-cell divisions in development Biotechnol. 2004;22:53-54. a far-reaching impact on the overall health and cancer. Nature. 2006;441(7097):1068-1074. 22. Ilancheran S, Michalska A, Peh G, et al. of the human race. Many people, profes- 8. Chambers I, Colby D, Robertson M, et Stem cells derived from human fetal membranes sional and lay alike, obtain their knowledge al. Functional expression cloning of Nanog, a display multilineage differentiation potential. from sources that present personal agendas pluripotency sustaining factor in embryonic stem Biol Reprod. 2007;77:577-588. or dubious interpretations of facts. In this cells. Cell. 2003;113:643-655. 23. Sinden JD. ReNeuron Group PLC. Regen. article, we have endeavored to give a fair, bal- 9. Nature Reports. How does a fertilized egg de- Med. 2006;1(1):143-147. anced, and unbiased view—as much as our velop? United Kingdom, 2007. Available at: http:// 24. 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Bernier PJ, Vinet J, Cossette M, et al. Char- Available at: http://www.whitehouse.gov/news/ acterization of the subventricular zone of the REFERENCES releases/2001/08/20010809-2.html. Accessed adult human brain: evidence for the involvement 1. National Commission on Health Educa- June 5, 2007. of Bcl-2. Neurosci Res. 2000;37(1):67-78. tion Credentialing, Inc. (NCHEC). About the 12. Offi ce of the Press Secretary. President 27. Leung CT, Coulombe PA, Reed RR. Con- National Commission on Health Education discusses stem cell research policy. United States, tribution of olfactory neural stem cells to tissue Credentialing. United States, 2002. Available at: 2006. Available at: http://www.whitehouse.gov/ maintenance and regeneration. Nat Neurosci. http://www.nchec.org/aboutnchec/rc.htm. Ac- news/releases/2006/07/20060719-3.html. Ac- 2007;10:720-726. cessed May 9, 2007. cessed June 5, 2007. 28. Yamashima T, Tonchev AB, Yukie M. 2.Yu J, Thomson JA. Embryonic stem cells. 13. De Anna G. Cloning, begetting, and mak- Adult hippocampal neurogenesis in rodents and In: Regenerative Medicine. Stem Cell Information ing children. HEC Forum. 2006;18(2):172-188. primates: endogenous, enhanced, and engrafted. from the National Institutes of Health Resource 14. Galletti M. Begetting, cloning and being Rev Neurosci. 2007;18(1):67-82. 176 American Journal of Health Education — May/June 2008, Volume 39, No. 3 AAJJOOHHEE MMaayy--JJuunnee 0088 IIPPCC..iinndddd 117766 44//3300//0088 66::2277::0000 PPMM PPrroocceessss BBllaacckk

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