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Stem Cells Technology

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Stem cell technology overview In order to gain a better understanding of the many benefits as well as the concerns raised by stem cells research, it is important to first have a general idea of what stem cells are, along with the specific properties the different categories of stem cells possess that make them such a valuable commodity to modern medicine today. Stem cells contain human DNA, and as a result make up the basic building blocks of human organisms. This essentially gives them “unique regenerative abilities”. In that sense they are unspecialized cells “capable of dividing and renewing themselves” into most, if not all of the cell types found in the human body. Three different types of stem cells have been identified by scientists. Not necessarily in order of importance, they start from the embryonic group which carries the greatest potential for becoming any other cell types and as a result, the greatest subject of controversy. The other two types of stem cells are the adult stem cells, which are to a degree less useful and can only become one of a few cell types; and the induced pluripotent stem cells which are specially treated cells that can be processed to behave somewhat like embryonic stem cells. Induced pluripotent stem cells commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell - typically an adult somatic cell - by inducing a "forced" expression of specific genes. Stem cell research by the way happens to be one of the most important medical and scientific areas of study today. Each new discovery related to their use has indeed moved the medical community one step closer to finding treatments for many life-threatening conditions and diseases.
Unique properties and applications of Embryonic stem cells Beyond a general description of stem cells, a detailed analysis of their anatomy, behavior, and most importantly their role in medical research will help gain a better understanding of their importance. Beginning with embryonic stem cells, as their name suggests, they are derived mostly from embryos that develop from eggs. Those eggs are typically fertilized in an “in vitro” environment, before being donated for research purposes with informed consent of the donors. It is important to stress here that those eggs are not derived from eggs fertilized in a woman's body. In vitro fertilization is a technique that unites the egg and sperm in a laboratory instead of inside the female body. The term “in vitro” has its roots from the Latin for "in glass", meaning in a laboratory dish or test tube, and suggesting an artificial environment. From their onset, embryonic stem cells are essentially undifferentiated cells derived from a 5-day preimplantation embryo that have the potential to become a wide variety of specialized cell types. The term “undifferentiated” refers to the cells’ preliminary state during which they have not yet assumed all the functional characteristics they will eventually acquire when they become specialized. Looking further embryonic stem cell technology, these particular stem cell lines are cultures of cells derived from the epiblast tissue of the inner cell mass of a blastocyst or earlier morula stage embryos. A blastocyst is nothing more than an early stage embryo that is approximately four to five days old in humans and consisting of anywhere from fifty to one hundred fifty cells. An important characteristic of embryonic stem cells worth mentioning is that they are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than two hundred cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta. Pluripotency in the broad sense refers to having more than one potential outcome. In biological systems, this often refers either to cells or to biological compounds. The term is derived from the Latin “pluri” meaning many, and potent meaning power, or capacity. A pluripotent cell can create all cell types except for extra embryonic tissue. This is in contrast with “totipotent” cells (“tot” meaning all), which can produce every cell type including extra embryonic tissue.

The Background and History of Embryonic Stem Cells In terms of the background and history of embryonic stem cells, their study has essentially been in existence throughout the past century, when doctors and scientists began trying to find a cure for the common, yet deadly diseases such as Parkinson’s, Alzheimer’s, and AIDS. With the introduction of microscopes in 1800’s, the curious minds of biologists all over the world could not help but dig further into what might have once been a mystery in medical research. In doing so, they discovered that cells are the building blocks of life, capable of giving rise to other cells and were effectively the key to understanding human development. Later, in the 1900’s, scientists noticed that cells such as red blood cells, white blood cells, and platelets all came from a certain cell: a stem cell. From there, it did not take very long to discover the unique ability of embryonic stem cells to transform into many different cells in the human body. This concept resulted in striking up quite a controversy from its beginning. The following will help gain a better understanding as to the reason for this controversy. When harvested, the embryonic stem cells are taken during the blastocyst stage into the development cycle. The problem arising from this process is that once taken from the embryo, the embryo is sacrificed and in fact dies. Furthermore, once obtained, these cells can be injected into anyone to grow specific cells in their body that aren’t necessarily being produced to the proper amount for the body to function normally. Historically the controversy behind embryonic stem cell research is in no way concerned with adult stem cells, which differ from embryonic stem cells because adult cells are cells that are already developed; they are taken from different parts of the body, and nothing dies in the process of retrieving them. Currently these cells are known to have been used in rare cases and have proven to cure diseases previously thought to be incurable. Taken from specialized areas in the body including the brain, the bone marrow, blood vessels, skin, and liver, adult stem cells’ main function are to repair and maintain the tissues they are taken from. The history of research on adult stem cells began about half a century ago, when researchers discovered that the bone marrow contains at least two kinds of stem cells: “hematopoietic stem cells” which form all the types of blood cells in the body, and “bone marrow stromal stem cells”, also known as skeletal stem cells which have the ability to generate bone, cartilage, fat, cells that support the formation of blood, and fibrous connective tissue. Research on adult stem cells has since generated a great deal of excitement, especially when scientists discovered the presence of adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for the last 40 years. Today, research indicates there is evidence that stem cells exist in the brain and the heart. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may very well become the basis of transplantation-based therapies.

Evolution from an early study in mouse embryos to human’s embryos A thorough analysis of the study on stem cells would not be complete without also examining its evolution from the initial mouse embryos to human’s embryos. For starters, one particular fact worth noting is that the general difficulty in obtaining suitable samples for study has in the past somewhat impeded our understanding of early human development as we know it today. Because of this, more emphasis and reliance has been placed on animal models of development, namely the mouse. Fact is, the mouse is a perfect model organism to study mammalian, and thus indirectly also human, embryology. Most scientific achievements that have had an important impact on the understanding of basic mechanisms governing embryo development in humans, originated from mouse embryology. Stem cell research, which now offers the promise of regenerative medicine, began with the isolation and culture of mouse embryonic stem cells. The very recent availability of human embryonic samples for gene expression studies has permitted for the first time an adequate assessment of the degree to which we can confidently extrapolate from rodent gene expression patterns. By the beginning of the 21st century, we still knew more about mouse development than we did about our own. Today, scientists still face many challenges in studying cell fate in developing human embryos, and for obvious reasons. The next best model for these studies would be to observe the behavior of embryonic cells in the context of an actual embryo. This is accomplished in the context of mouse embryos.
The choice of merging human and mouse embryonic cells has made scientific sense considering the molecular and cellular aspects of mouse development, and has been the subject of intense scrutiny for the past few decades. Thus, the mouse embryo presents a platform in which the molecular basis of human embryonic differentiation can be quantitatively tested. What logically followed was a series of experiments combining mouse and human embryonic cells and designed to test whether human embryonic stem cells could thrive in a mouse embryo. The bottom line here is the fact that human and mouse embryonic cells effectively share basic mechanisms of differentiation. This has provided a critical first step to both a basic understanding of human development and to the clinical use of human embryonic stem cells. Throughout the course of the past two decades, more recent advances in genetics and genome sequence information has made mouse an extremely valuable model for understanding mammalian development. That said, the disparity in morphological and molecular changes between mouse and human embryos almost to a degree, dictates that it is important to carry out, to the maximum extent possible, research directly on human embryos. On the other hand, we cannot help but take into account the many and obvious ethical concerns that make human embryonic tissues hard to obtain. The two recent microarray analyses on human embryogenesis have provided the first glimpse on the global gene expression profiles during human organogenesis and revealed important information for understanding the molecular pathways of human embryonic development. More importantly, the database for the gene expression profiles of the 4th to 9th weeks of human development appears to function as a valuable resource for identifying novel genes involved .At the same time it would help to predict the potential roles of developmentally regulated genes during organogenesis witch is a critical period with little prior molecular knowledge. An even more pressing task is to further improve and expand our database as more information on human development is collected with the development of new technologies. This should enhance the value of the database for studying the molecular basis of human development. Finally, it is also worth mentioning that the most significant morphological differences between mouse and human development appear during organogenesis. The human gene expression composition could assist in the determination of the molecular basis underlying the conservations and evolutionary divergences between mouse and human development. Once the transcriptome analyses of corresponding period of mouse embryos are carried out, this advances in mouse genetics, will be extremely useful for future functional dissections of the molecular mechanisms underlying mammalian organogenesis. Since 1998 more than 1,200 different human embryonic stem cell lines have been established worldwide, and there is still a recognized interest in the establishment of new lines, particularly ethnic groups underrepresented among the currently available lines. The methodology of human embryonic stem cell origin has since evolved significantly from its initial stages. However, there are still a number of alternative strategies being sought for the different steps involved in establishing yet more lines of human embryonic stem cells. Various new strategies and parameters used between 1998 and 2010 for the root of the current lines are continuously being developed. While mice are not always reliable as preclinical models for human disease, -and we can’t help but notice how much the scientific literature is being littered with examples of drugs that worked well in animals but turned out to be ineffective in clinical trials on humans - research has led to major advances in our ability to treat a number of serious diseases and conditions. For instance, work on mice resulted in successful treatments for a particular type of cancer (acute promyelocytic leukemia,) that was previously largely untreatable. Indeed, 99% of mouse genes have an equivalent in humans, making mice ideal for studying the function of human genes in many other diseases such as cardiovascular diseases and diabetes. In recent years we have actually seen a rise in the use of genetically engineered mice in research and preclinical studies. Some of these models can mimic a wide range of human diseases and health problems. In addition, the mouse is so far the only mammalian model in which it is technically possible to generate an organism in which a particular mouse gene has been replaced by its human counterpart.
Environmental effects More often than not little communication historically has been exchanged between the ethicists and scientists constituencies with regards to the debate on the uses and potentials of human stem cells. As a result, there is no arguing the ethicists are not as well informed on the issue as are the scientists. In trying to understand the significant roles the environment plays in identifying the various cell types as well as subtypes, it is important to highlight the scientific insights that may to some degree be relevant to ethical debate. Particularly as it relates to the role played by the microenvironment in stem cell studies, research indicates there has been much emphasis placed on “plasticity”. The term “plasticity” refers to the process under which one type of cell has the unique ability to undergo a transition to cells from other lineages, and therefore taking the characteristics of those new cells. This can be especially useful to modern medicine, as such a process offers new hope for potentially treating diseased internal organs by way of regenerating tissue. We should recall the distinct difference between pluripotency and totipotency, and that difference becomes of even greater importance in trying to understand the effects of the environment on stem cell behavior. It is argued that early embryos or blastocysts, as well as embryonic stem cells simply remain in a pluripotent state if not maintained in the appropriate environment. Conversely, those same cells will display totipotent characteristics when developed in a suitable environment: the laboratory. While blastocysts within the human body are actually already totipotent, their counterparts in the laboratory carry that potential. In addition to the physical environmental factors, ongoing research on stem cells has provided some new insights about a possible relationship between exposure to certain specific chemicals and human development, down to a child’s ability to learn. In fact, there may be a direct connection between those chemicals and neonatal development. Moreover, there is hope continued research on stem cells may soon lead to the eventual isolation of a family of chemicals that will have the capability of enhancing human brain development. In the study of stem cell science as a whole, a good majority of the work involved has been is concerned with the chemical microenvironment. Such an environment plays a critical role in guiding stem cells through the differentiation process, from a blank state through specific cell types. To date there are still mysteries surrounding the behavior of stem cells in terms of how they sense and respond to specific variable and manipulated tissue, physiological, and other external environments. That said, significant progress has been made in recent years that shed some new light on how the environment as a whole essentially controls their activity and maintenance. In essence the microenvironment that nurtures stem cells has a direct influence on their fate.

References
Betts, K. S. (2010, October 1). Growing knowledge: Using stem cells to study developmental neurotoxicity. Environmental Health Perspectives, sec.118:a432-a437. Retrieved from http://ehp03.niehs.nih.gov/article/info%3Adoi%2F10.1289%2Fehp.118-a432
Duffy, D. T. (2002, June 12). Background and legal issues related to stem cell research. Retrieved from Almanac of Policy Issues database.
Pub Med Central. (in press). Core transcriptional regulatory circuitry in human embryonic stem cells. . Retrieved from NHI Public Access database. (PMC3006442)
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998, November 6). Embryonic stem cell lines derived from human blastocysts (Science volume 282 No. 5391). doi:10.1126/science.282.5391.1145
What are the unique properties of all stem cells? (2009, April 28). Stem cell basics [Stem cell information]. Retrieved from National Institutes of Health, U.S. Department of Health and Human Services website: http://stemcells.nih.gov/info/basics/basics2.asp

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