A major goal of scientific research is the acquisition of reliable knowledge based on experiments that yield reproducible results. Reproducible results are possible only if the materials used in experiments remain constant and stable. To obtain reproducible results in experiments using stem cells, it is essential to produce, preserve, characterize, and continually re-characterize preparations of stem cells in ways that increase the likelihood that the cells used to repeat experiments will remain unchanged—a technically challenging task. The tendency of stem cells in vitro to differentiate spontaneously into more specialized cells makes the task of obtaining homogeneous and stable stem cell preparations especially challenging, and much basic research is needed to learn how to control the fate of these cells. Failure to control the cells may yield experimental results that are difficult or impossible to reproduce. The following more specific observations make clear the dimensions of this difficulty.
A. Initial Stem Cell Preparations Can Contain Multiple Cell Types
Isolation of adult stem cells from source tissues such as bone marrow, brain, or muscle initially yields a heterogeneous cell preparation. The initial preparation contains the several cell types found in the source tissue, and it may also include red blood cells, white blood cells, and (possibly) circulating stem cells, owing to the presence of blood flowing through the tissue in question. Initial mixtures of cells may then be treated in various ways to remove unwanted contaminating cells, thereby increasing the proportion of stem cells in the preparation. But seldom, if ever, does one produce an adult stem cell preparation that is 100 percent stem cells, unless the adult stem cell preparation has been “single-cell cloned” in vitro (see below).The way in which human embryonic stem cells have been produced from ICM cells also raises a question about the “species homogeneity” of the initial cell preparations. In the past, human embryonic stem cells were isolated and maintained by in vitro growth on top of irradiated (so that they no longer divide) “feeder layers” of mouse cells. It is thought that the feeder cells secrete factor(s) that enable the stem cells to divide while maintaining a relatively undifferentiated state. Although the mouse cells have been treated to prevent their cell division, should any of them happen to survive, human embryonic stem cells prepared in this way may contain some viable mouse cells.vi More recently, several groups have shown that it is possible to grow ESCs on feeder layers of human cells, including fibroblasts obtained from skin biopsies, or without any feeder cell layer at all.11 One way to be certain that human embryonic stem cell preparations do not contain any mouse feeder cells is through “single cell cloning” (see below).
B. Genetically Homogenous Stem Cells through Single Cell Cloning
Some preparations of stem cells growing in vitro have been “single cell cloned,” that is, grown as a population derived from a single stem cell. By placing a cylinder over a single cell located with a microscope, scientists are able to isolate within the cylinder all the progeny produced by subsequent cell divisions beginning from this single cell. The result is a stem cell preparation in which all the cells are descended from the original single cell. The cells within the cylinder are then harvested and grown to greater numbers in vitro, and the resulting stem cell preparation is said to be “single cell cloned.” The stem cells within a “single cell cloned” population are, at least to begin with, genetically homogeneous because they are all derived from the same original cell. Some of the ESC preparations produced prior to August 9, 2001 have been “single cell cloned.”12
C. Expansion in Vitro, Preservation, and Storage
Reproducible results require that preparations of stem cells, even if genetically homogenous when first isolated, remain stable over time and during preservation. This, too, is not a simple matter with stem cells, despite the fact that the self-renewal characteristic of human embryonic and adult stem cells enables them—unlike differentiated cells from many human tissues—to be grown in large numbers in vitro while maintaining their essential stem cell characteristics. After such expansion, many, presumably identical, vials of the cells can be frozen and preserved at very low temperatures. Frozen stem cell preparations can later be thawed and grown again in vitro to produce larger numbers of cells. As with all dividing cells, stem cells are subject to a very small but definite chance of mutation during DNA replication; thus, prolonged growth in vitro could introduce genetic heterogeneity into an originally homogeneous population. During this process of repeated expansion and preservation, subtle changes in the growth conditions or other variables may give rise to “selective pressures” that can increase the heterogeneity in a stem cell preparation by favoring the multiplication of advantaged cell variants in the population. It is not known at present how many of the 78 human ESC preparations, designated as eligible for federal funding under the current policy, have developed genetic variants that may make them unsuitable for further research.Whether several cycles of freezing and thawing change the phenotypic characteristics of stem cell preparations needs detailed study. However, the practical advantages of preserving stem cell preparations by freezing are too large to ignore. Such preservation makes it possible to repeat an experiment many times with a very similar stem cell preparation. It would also make it possible, should stem cell based therapies be developed in the future, to treat multiple patients with a common, well-characterized cell preparation derived from a single initial stem cell sample.
D. Chromosome Changes
In addition to the possible loss of homogeneity in stem cell preparations owing to variability in growth conditions or to freezing and thawing, there is the possibility of variation being introduced during the processes of growth and cell division. Normal human stem cells (like all human somatic cells) have 46 chromosomes. During the copying of chromosomal DNA and the separation of daughter chromosomes at cell division, rare mistakes occur that lead to the formation of abnormal chromosomes or maldistribution of normal ones. Cells with abnormal chromosomes or chromosome numbers can progress to malignancy, so retention of the normal human chromosome number and structure is an essential characteristic of useful human stem cell preparations. The most studied preparations of human stem cells generally have normal human chromosome numbers and structure.vii Nevertheless, vigilance is needed, for even a small number of chromosomally abnormal cells could end up causing cancer in future clinical trials of stem cell based therapies.
E. Developmental Heterogeneity of Stem Cell Preparations
The in vitro growth conditions and the presence of specific chemicals or proteins, or both, in the culture medium can influence the differentiation pathway taken by stem cells as they start to differentiate. Thus, even initially homogeneous, “single cell cloned” stem cell preparations may become developmentally heterogeneous over time, with respect to the percentage of cells in the preparation that are in one or another differentiated state. For example, a stem cell preparation after growth in vitro under specific conditions might contain 75 percent fully differentiated (insulin-producing) cells and 25 percent partially differentiated cells. The biological properties of the fully differentiated cells and the partially differentiated cells are likely to be different. If such a cell preparation is used in research, or transplanted into an animal model of human disease and a biological effect is observed, one must do additional experiments to determine whether the effect was due to the fully differentiated cells or to the partially differentiated cells (or perhaps to both acting together) in the now mixed preparation.
F. Microbial Contamination
Stem cell preparations originally isolated from humans and expanded in vitro may also be variably contaminated with human viruses, bacteria, fungi, and mycoplasma. ESC preparations isolated using mouse feeder cell layers might also be contaminated with mouse viruses. Specific tests need to be performed on the source tissue and periodically on the resulting stem cell preparations to rule out the presence of these contaminants. Some of these contaminants can also multiply when stem cells are grown in vitro, and their presence can influence the results obtained when stem cell preparations are used in subsequent experiments. The presence of such contaminants can also potentially affect the reproducibility of the results of experiments in which stem cell preparations are studied in vivo in experimental animals.
In summary, there are numerous challenges to obtaining and preserving the uniform and stable preparations of stem cells necessary for reliable research and, eventually, for safe and effective possible therapies. Researchers must address multiple factors in order to maximize the probability of obtaining reproducible results with human stem cell preparations. Human stem cell preparations that are
“single cell cloned,” with a normal chromosome structure and number, and
stored as multiple samples that are preserved at very low temperature, and
compared in experiments where cells from the same lot of frozen material are used, and
well-characterized as to the absence of cellular, viral, bacterial, fungal, and mycoplasma contaminants, and
tested to determine the proportion of stem cells and various differentiated cells in the cell preparation used in the experiments, are most likely to yield experimental results that will be reproducible. Preparations with these properties will be the most useful both in basic research and in investigations of possible clinical applications.
Sunday, August 3, 2008
I. Stem Cells and Their Derivatives
The adult human body, and all its differentiated cells, tissues, and organs, arise from a small group of cells contained within the early embryo at the blastocyst stage of its development. During in vivo embryonic development, these cells, constituting the inner cell mass (ICM), will divide and differentiate in concert with each other and with the whole of which they are a part, eventually producing the specialized and integrated tissues and organs of the body. But when embryos are grown [using in vitro fertilization (IVF)] in a laboratory setting, these ICM cells may be removed and isolated, and under appropriate conditions some will proliferate in vitro and become embryonic stem cell lines. These embryonic stem cells are capable of becoming many different types of differentiated cells if stimulated to do so in vitro [see endnote 2 for references]. However, it is not yet clear that the cells that survive the in vitro selection process to become embryonic stem cells have all of the same biological properties and potentials as the ICM cells of the blastocyst.7 In particular, it is not known for certain that human embryonic stem cells in vitro can give rise to all the different cell types of the adult body.iiAs noted in the Introduction to this report, stem cells are a diverse class of cells, which can now be isolated from a variety of embryonic, fetal, and adult tissues. Stem cells share two characteristic properties: (1) unlimited or prolonged self-renewal (that is, the capacity to maintain a pool of stem cells like themselves), and (2) potency for differentiation, the potential to produce more differentiated cell types—usually more than one and, in some cases, many.iii
When stem cells head down the pathway toward differentiation, they usually proceed by first giving rise to a more specialized kind of stem cell (sometimes called “precursor cells” or “progenitor cells”), which can in turn either proliferate through self-renewal or produce fully specialized or differentiated cells .
When stem cells head down the pathway toward differentiation, they usually proceed by first giving rise to a more specialized kind of stem cell (sometimes called “precursor cells” or “progenitor cells”), which can in turn either proliferate through self-renewal or produce fully specialized or differentiated cells .
figure is an undifferentiated stem cell; in the central box are more “specialized” stem cells (or “precursor cells” or “progenitor cells”); at the bottom are various differentiated cells that are derived from the specialized stem cells. Dashed arrows indicate symmetrical (in the sense that both the daughter cells are stem cells) cell divisions that produce more stem cells (self-renewal). Solid arrows indicate asymmetric cell divisions that produce more differentiated daughter cells. (There may also be self-renewal with asymmetric division—not shown here—in which one daughter cell initiates a differentiation pathway while the other remains a stem cell.) Differentiation signals can be supplied by both soluble proteins and by specific, cell-surface binding sites. Some of the specialized stem cells inside the dashed box, for example, mesenchymal stem cells, can be isolated from tissues after birth and correspond to adult stem cells. Scientists are currently investigating whether, at least in some cases, the process can be reversed, that is, whether specialized cells may, on appropriate signals, dedifferentiate to become precursor or even fully undifferentiated stem cells.The terminology used to describe different stem cell types can be confusing. As used in this chapter, stem cells are self-renewing, cultured cells, grown and preserved in vitro, that are capable—upon exposure to appropriate signals—of differentiating themselves into (usually more than one) specialized cell types. Stem cells may be classified either according to their origins or according to their developmental potential. Stem cells may be obtained from various sources: from embryos, from fetal tissues, from umbilical cord blood, and from tissues of adults (or children). Thus, depending on their origin, stem cell preparations may be called adult stem cells,iv embryonic stem cells, embryonic germ cells, or fetal stem cells. Adult stem cells [see (4)] are cells derived from various tissues or organs in humans or animals that have the two characteristic properties of stem cells (self-renewal and potency for differentiation). Embryonic stem cells (ESCs) [see (2)] are derived from cells isolated from the inner cell mass of early embryos. Embryonic germ cells (EGCs) [see (1)] are stem cells derived from the primordial germ cells of a fetus. Fetal stem cells (not further discussed in this chapter, but included for the sake of completeness) are derived from the developing tissues and organs of fetuses; because they come (unlike EGCs) from already differentiated tissues, they are (like adult stem cells) “non-embryonic,” and may be expected to behave as such.Depending on their developmental potential, cells may be called pluripotent, multipotent, or unipotent. Cells that can produce all the cell types of the developing body, such as the ICM cells of the blastocyst, are said to be pluripotent. The somewhat more specialized stem cells, of the sort found in the developed organs or tissues of the body, are said to be multipotent if they produce more than one differentiated tissue cell type, and unipotent if they produce only one differentiated tissue cell type. We introduce in this chapter an additional term: stem cell preparation. A stem cell preparation is a population of stem cells, prepared, grown, and preserved under certain conditions. Because different laboratories (or even the same one) can have different preparations of the same type of stem cell, it is important to recognize the potential differences between particular preparations of embryonic stem cells.v It will sometimes be important to call attention to this fact, by speaking of a “preparation of ES cells” (or a preparation of adult stem cells) rather than of “ES cells,” pure and simple. We will use the term “stem cell preparations” when we are speaking of a diverse group of stem cell cultures, when we are speaking of stem cell cultures that contain an admixture of other types of cells, or when the developmental homogeneity of the stem cells in the population has not been defined.Adult and embryonic stem cell populations have also been called “stem cell lines.” In the past, the term “cell line” denoted a cell population (usually of cancer cells containing abnormal chromosome numbers or structure, or both) that could grow “indefinitely” in vitro. Embryonic and some adult stem cell preparations are capable of prolonged growth beyond 50 population doublings in vitro while retaining their characteristic stem cell properties and initially with no change in the chromosome numbers and structure. It is not yet known whether any preparation of human ES cells (generally believed to be much longer-lived than adult stem cells) will continue to grow “indefinitely,” without undergoing genetic changes.Under the influence of various cell-differentiation signals, embryonic stem cells differentiate into numerous distinct types of more specialized cells. Some of these are specialized stem cells that can also self-renew, while retaining their ability also to differentiate into multiple cell types. Recent research has led to the isolation of an increasing number of adult (non-embryonic) stem cells (dashed box area of Figure 1) from such tissues as bone marrow (for example, hematopoietic and mesenchymal stem cells), brain (for example, neural stem cells) and other tissues [see (4)]. Although these stem cell preparations differ from one another in their future fates, they tend to be grouped together (especially in the public policy debates) under the name “adult stem cells,” even though they may have been obtained from children or even from umbilical cord blood obtained at the time of childbirth.Subsequent exposure to additional differentiation signals can cause these specialized stem cells to differentiate further, so that they finally give rise to the variety of differentiated cells that make up the adult body (labeled A-D in Figure 1). At each stage of the differentiation process, specific sets of genes are expressed (or “turned on”) and other sets are repressed (or “turned off”), to produce the specific proteins that give each cell its distinctive properties. At each stage along the way, proteins called transcription factors play key roles in determining which sets of genes are expressed and repressed, and therefore what sort of a cell the newly differentiated cell will become.
Recent Developments in Stem Cell Research and Therapy
Research using human and animal stem cellsi is an extremely active area of current biomedical inquiry. It is contributing new knowledge about the pathways of normal and abnormal cell differentiation and organismal development. It is opening vistas of new cell transplantation therapies for human diseases. Although the availability of a variety of human stem cells is relatively recent—the isolation of human embryonic stem cells was first reported only in 1998—much is happening in both publicly funded and privately funded research centers around the world. It is difficult for anyone to stay abreast of all the results now rapidly accumulating.To help us fulfill our mandate to “monitor stem cell research,” the President’s Council on Bioethics asked several experts to survey the recent published scientific literature and to contribute articles on various areas of stem cell research to this report (see articles by Drs. Gearhart,1 Ludwig and Thomson,2 Verfaillie,3 Prentice,4 Itescu5, 6 and Jaenisch7 in the Appendices). These reviews and the present chapter emphasize peer-reviewed, published work with human stem cells through July 2003. Interested readers should also consult the wide variety of other review articles that have appeared.8This chapter should be read in conjunction with the commissioned review articles cited above. It draws on their findings, as well as on the Council’s own monitoring activities, but it makes no attempt to summarize all the complexity of stem cell research or the vast array of results. Rather we offer here some general observations and specific examples that might help non-scientist readers understand the overall state of present human stem cell research, its therapeutic promise, and some of the problems that need to be solved if the research is to yield sound knowledge and clinical benefit. To that end, we highlight the importance of well-characterized, stable preparations of stem cells for obtaining reproducible experimental results, and we identify several problems that must be solved before these requirements can be fully met. This chapter then describes, by way of illustration and example, some of the better-characterized adult and embryonic stem cells. It also indicates some of the specific investigations that are being conducted with their aid. Finally, it considers how human stem cells are being used to explore their potential for treating disease, using experiments in animal models of Type-1 diabetes as an example, and it points out some of the difficulties that must be overcome before stem cell-based remedies may be available to treat human diseases.We confine our attention here to newly identified types of human stem cells and their potential use in research and future medical treatment. Accordingly, we do not consider those stem cell types that are already well established in medical practice and research. Specifically, we will not examine those preparations of bone marrow cells that have been clinically used for some years to treat various forms of anemia and cancer.9 Neither will we deal with hematopoietic (blood-forming) stem cells that have been isolated and purified from bone marrow and are now being intensively studied.10 Although these developments lie beyond the scope of this report, the demonstrated usefulness of these cells for research and therapy encourages many researchers to expect similar benefits from the newer stem cells that we shall consider here.
I. Stem Cells and Their Derivatives
The adult human body, and all its differentiated cells, tissues, and organs, arise from a small group of cells contained within the early embryo at the blastocyst stage of its development. During in vivo embryonic development, these cells, constituting the inner cell mass (ICM), will divide and differentiate in concert with each other and with the whole of which they are a part, eventually producing the specialized and integrated tissues and organs of the body. But when embryos are grown [using in vitro fertilization (IVF)] in a laboratory setting, these ICM cells may be removed and isolated, and under appropriate conditions some will proliferate in vitro and become embryonic stem cell lines. These embryonic stem cells are capable of becoming many different types of differentiated cells if stimulated to do so in vitro [see endnote 2 for references]. However, it is not yet clear that the cells that survive the in vitro selection process to become embryonic stem cells have all of the same biological properties and potentials as the ICM cells of the blastocyst.7 In particular, it is not known for certain that human embryonic stem cells in vitro can give rise to all the different cell types of the adult body.iiAs noted in the Introduction to this report, stem cells are a diverse class of cells, which can now be isolated from a variety of embryonic, fetal, and adult tissues. Stem cells share two characteristic properties: (1) unlimited or prolonged self-renewal (that is, the capacity to maintain a pool of stem cells like themselves), and (2) potency for differentiation, the potential to produce more differentiated cell types—usually more than one and, in some cases, many.iii
When stem cells head down the pathway toward differentiation, they usually proceed by first giving rise to a more specialized kind of stem cell (sometimes called “precursor cells” or “progenitor cells”), which can in turn either proliferate through self-renewal or produce fully specialized or differentiated cells
I. Stem Cells and Their Derivatives
The adult human body, and all its differentiated cells, tissues, and organs, arise from a small group of cells contained within the early embryo at the blastocyst stage of its development. During in vivo embryonic development, these cells, constituting the inner cell mass (ICM), will divide and differentiate in concert with each other and with the whole of which they are a part, eventually producing the specialized and integrated tissues and organs of the body. But when embryos are grown [using in vitro fertilization (IVF)] in a laboratory setting, these ICM cells may be removed and isolated, and under appropriate conditions some will proliferate in vitro and become embryonic stem cell lines. These embryonic stem cells are capable of becoming many different types of differentiated cells if stimulated to do so in vitro [see endnote 2 for references]. However, it is not yet clear that the cells that survive the in vitro selection process to become embryonic stem cells have all of the same biological properties and potentials as the ICM cells of the blastocyst.7 In particular, it is not known for certain that human embryonic stem cells in vitro can give rise to all the different cell types of the adult body.iiAs noted in the Introduction to this report, stem cells are a diverse class of cells, which can now be isolated from a variety of embryonic, fetal, and adult tissues. Stem cells share two characteristic properties: (1) unlimited or prolonged self-renewal (that is, the capacity to maintain a pool of stem cells like themselves), and (2) potency for differentiation, the potential to produce more differentiated cell types—usually more than one and, in some cases, many.iii
When stem cells head down the pathway toward differentiation, they usually proceed by first giving rise to a more specialized kind of stem cell (sometimes called “precursor cells” or “progenitor cells”), which can in turn either proliferate through self-renewal or produce fully specialized or differentiated cells
The techniques for culturing mouse embryonic stem (ES) cells from the inner cell mass of the preimplantation blastocyst were first reported 20 years ago , and versions of these standard procedures are used today in laboratories throughout the world. Additionally, studies of embryonal carcinoma (EC) cells from mice and humans have helped establish parameters for growing and assessing ES cells. It is striking that, to date, only three species of mammals have yielded long-term cultures of self-renewing ES cells: mice, monkeys, and humans (see Figure . Origins of Mouse Pluripotent Stem Cells).
The production of formed elements, or blood cells, is called hemopoiesis. Before birth, hemopoiesis occurs primarily in the liver and spleen, but some cells develop in the thymus, lymph nodes, and red bone marrow. After birth, most production is limited to red bone marrow in specific regions, but some white blood cells are produced in lymphoid tissue.
All types of formed elements develop from a single cell type -- stem cell (pleuripotential cells or hemocytoblasts). Seven different cell lines, each controlled by a specific growth factor , develop from the hemocytoblast. When a stem cell divides, one of the "daughters" remains a stem cell and the other becomes a precursor cell, either a lymphoid cell or a myeloid cell. These cells continue to mature into various blood cells.
A leukemia can develop at any point in cell differentiation. The illustration below shows the development of the formed elements of the blood
All types of formed elements develop from a single cell type -- stem cell (pleuripotential cells or hemocytoblasts). Seven different cell lines, each controlled by a specific growth factor , develop from the hemocytoblast. When a stem cell divides, one of the "daughters" remains a stem cell and the other becomes a precursor cell, either a lymphoid cell or a myeloid cell. These cells continue to mature into various blood cells.
A leukemia can develop at any point in cell differentiation. The illustration below shows the development of the formed elements of the blood
Human embryonic stem
Human embryonic stem (ES) cells are derived from human embryos that are 5 to 6 days old. At this stage of development the embryo is a hollow ball of about 200 to 250 cells, no bigger than a pinhead, and is called a blastocyst. Within the blastocyst is a small group of 30 to 34 cells, called the inner cell mass. These inner mass cells are able to develop into any type of cell (pluripotent) and are the source of all the highly specialised cells found in an adult organism. The remaining cells generate all other tissues such as the foetal membranes and placenta.
Australian Stem Cell Centre
Once the inner mass cells are obtained, they may be used to create pluripotent stem cell ‘lines’ – cell cultures that can be grown indefinitely in the laboratory. These lines are important tools for scientists, as they are all the same and it means new cells do not need to be isolated every time they want to do an experiment.
It is illegal in Australia to conduct any type of research on embryos that are conceived naturally. ES cells are taken from embryos that come from eggs fertilised in an IVF (in vitro fertilisation) clinic. Only embryos not required for implantation are used. They are donated for research purposes only with informed consent from the donors. They are not derived from eggs fertilised within a woman’s body, and embryos are not created specifically for research purposes.
ES cells can become any cell type of the body because they are pluripotent, making them attractive for developing different tissues for cell-based therapies.
Large numbers of embryonic stem cells can be grown in the laboratory relatively easily. ES cell lines are sometimes referred to as immortal, due to their ability to keep dividing (self-renew) over many generations. Therefore established cell lines can be maintained in laboratories for further research and generation of cells for cell-based therapies for many years.
Human embryonic stem cells could be used to seek out and destroy a fatal form of brain cancer. Experiments in mice with brain tumours show that the cells will migrate across the brain and deliver an anti-cancer payload.
ES cells may have great potential in forming the basis of long-term therapies, but issues regarding their safety must be overcome first. It is not yet known how transplanted ES cells would behave inside the body, but scientists are particularly worried that the transferred ES cells might not stop dividing. This uncontrolled growth may generate tumours, and this has already been shown to occur in laboratory cultures. While the cells in these tumours are benign, scientists do not know how they might behave in the body. However, cells differentiated from ES cells have been used in a number of studies, and have developed normally. This issue must be fully explored before clinical trials can proceed in people.
Another issue with the use of ES cells in regenerative medicine is that they may trigger immune rejection by the patient’s immune system. A number of alternatives are being investigated to overcome this, including combining stem cell technology with cloning methods in a process called somatic cell nuclear transfer. This is discussed in the section on stem cells in cloning.
There are a range of opinions about ES cell research in the community. The overwhelming issue for most people opposed to ES cell research is that taking inner mass cells inevitably leads to the destruction of the embryo. For those that view a fertilised egg as a human life this is most distressing. Others consider the blastocyst to be nothing more than a ball of cells with the potential to become a human. Debate on this issue remains considerable and controversial.
Australian Stem Cell Centre
Once the inner mass cells are obtained, they may be used to create pluripotent stem cell ‘lines’ – cell cultures that can be grown indefinitely in the laboratory. These lines are important tools for scientists, as they are all the same and it means new cells do not need to be isolated every time they want to do an experiment.
It is illegal in Australia to conduct any type of research on embryos that are conceived naturally. ES cells are taken from embryos that come from eggs fertilised in an IVF (in vitro fertilisation) clinic. Only embryos not required for implantation are used. They are donated for research purposes only with informed consent from the donors. They are not derived from eggs fertilised within a woman’s body, and embryos are not created specifically for research purposes.
ES cells can become any cell type of the body because they are pluripotent, making them attractive for developing different tissues for cell-based therapies.
Large numbers of embryonic stem cells can be grown in the laboratory relatively easily. ES cell lines are sometimes referred to as immortal, due to their ability to keep dividing (self-renew) over many generations. Therefore established cell lines can be maintained in laboratories for further research and generation of cells for cell-based therapies for many years.
Human embryonic stem cells could be used to seek out and destroy a fatal form of brain cancer. Experiments in mice with brain tumours show that the cells will migrate across the brain and deliver an anti-cancer payload.
ES cells may have great potential in forming the basis of long-term therapies, but issues regarding their safety must be overcome first. It is not yet known how transplanted ES cells would behave inside the body, but scientists are particularly worried that the transferred ES cells might not stop dividing. This uncontrolled growth may generate tumours, and this has already been shown to occur in laboratory cultures. While the cells in these tumours are benign, scientists do not know how they might behave in the body. However, cells differentiated from ES cells have been used in a number of studies, and have developed normally. This issue must be fully explored before clinical trials can proceed in people.
Another issue with the use of ES cells in regenerative medicine is that they may trigger immune rejection by the patient’s immune system. A number of alternatives are being investigated to overcome this, including combining stem cell technology with cloning methods in a process called somatic cell nuclear transfer. This is discussed in the section on stem cells in cloning.
There are a range of opinions about ES cell research in the community. The overwhelming issue for most people opposed to ES cell research is that taking inner mass cells inevitably leads to the destruction of the embryo. For those that view a fertilised egg as a human life this is most distressing. Others consider the blastocyst to be nothing more than a ball of cells with the potential to become a human. Debate on this issue remains considerable and controversial.
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