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The essential account of the most important scientific advance and most volatile ethical debate of our time While many believe stem cell research holds the key to curing a wide range of ailments, others see this research as opening a Pandora's box that will devalue human life. Stem Cells and Society Program lays out the scientific and ethical issues surrounding this national dilemma.The latest advances in stem cell research in clear, accessible language, telling the stories of the researchers who are exploring the potential of stem cells to cure cancer, grow new organs, and repair the immune system. Stem Cell Now is essential reading for anyone who wants to build an informed opinion on stem cell research.Probably the most lucid and readable primer on the science and politics of stem cells. The hype of instant cures and pro-life antagonism to present the true breadth of stem cell research.
Because only of the properties of the stem cells, it has so many biotechnological application such as brain transplantation, bone marrow transplantation, etc are discussed in the essay. This essay also covers some latest news on stem cells like use in identification of breast cancer cells. The field of stem cell research will attracted many investigators for several years because of its self-renewable property and many other characteristics.
Stem cells: An Overview
There is still no universally acceptable definition of the term stem cell, despite a growing common understanding of the circumstances in which it should be used. According to more recent perspective, the concept of the 'stem cell' is indissolubly linked with the growth via the multiplication rather than the enlargement of the cells. Stem cells are class of undifferentiated cells that are able to differentiate into differentiate specialized cell types. Commonly, stem cells come from 2 main sources:
- Embryos forms during the blastocyts phase during the embryological development (embryonic stem cells) and
- Adult tissue (adult stem cells)
Both types are generally characterized by their potency and potential to differentiate in to different cell types ( such as bone, muscle, skin, etc).
Adult stem cells:
After embryogenic development adult or somatic cells exist throughout the body and are found inside of different types of tissues. These types of stem cells are found tissues like bone marrow, brain, liver, blood vessels, skin, and skeletal muscles. These types of cells are remain in non-dividing state for many years until its activated by any injury or disease. Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. On the base of tissue of origin of stem cells, stem cells have limit in their ability to differentiate but actually many evidences says that they can differentiate to other cell types.
Embryonic stem cells:
From a four or five days old human embryo, embryonic cells are derived that is in the blastocyts phase of the development. Usually these embryos are extras which are created in IVF (in vitro fertilization) clinics where some eggs are fertilized in test tubes, but only one is implanted in woman. Sexual production begins when a male's sperm fertilizes a female ovum (egg) to form a single cell called a zygote after that cell division begins.
Stem cells once extracted, either from adult tissue or from a zygote, it has to be put in the controlled culture that usually allows them to divide and replicate but it sometimes also put into controlled culture that prohibits for the further specialization and differentiation. It is easy to grow a large number of embryonic stem cells than adult stem cells but progress is being made for both types of cells. In a controlled culture once the stem cells are allow to divide and propagate then the collection of the healthy, dividing and undifferentiated cells is called a stem cell line. Stem cells are categorized by their potential of differentiate into other types of cells. So on this basis stem cells are categorized in five types i.e. 1. Totipotent 2. Pluripotent 3. Multipotent 4.oligopotent 5. Unipotent.
Most of tests are based on making sure that stem cells are undifferentiated and have the capability of self-renewable but there is no complete agreement among the scientists of how to identify the stem cells. In a lab there is one way to identify stem cells, and the standard procedure for testing bone marrow or hemapoietic stem cells (HSC), is by transplanting one cell to save an individual without HSCs. So after that it demonstrate its potency if stem cells produces a new blood and immune cells. Colonogenic essay is also a laboratory procedure for the identification of the stem cells. It can be employed in vitro to test whether single cell can differentiate and self renewable.
Stem cells therapies:
The opportunity for transplanting a live source for self regeneration is offered by stem cells.
Organ and tissue regeneration:
The most important possible application of the stem cell is the regeneration of the tissues. Osteogenesis imperfecta (OI) represents a debilitating genetic disease where the chromosomal defect lies in the collagen type I gene that is prominently expressed in osteocytes. Expression of the faulty gene causes systemic osteopenia resulting in bony deformities, skeletal fragility, and short stature. In 1999, three Infant OI patients were transfused with whole bone marrow from HLA-identical siblings, and the subsequent course of their disease was assessed during a 6-month follow-up (Horwitz et al. 1999). Osteoblasts were isolated from a bone biopsy and showed engraftment of donor mesenchymal cells. These patients had 20-37 fractures in the 6 months prior to infusion, but in the 6 months following transplantation their fractures were reduced to 2 and 3, respectively. All patients had increased total body mineral content. These patients also showed near-normal growth over this period. Although these are early results, they easily convey the promise that stem cell therapy may provide in the future.
Marrow-derived hMSCs (h-marrow stem cells) represent a useful, easily obtained, characterized cell population to explore mesenchymal tissue regeneration, and there is good evidence to suggest the cells can be used allogeneically. The hMSCs do express small amounts of the major histocompatiblity complex (MHC) class I molecule but express little or no MHC class II or B7 costimulatory molecules. In vitro experiments with lymphocytes from unrelated donors suggest that hMSCs do not elicit proliferation of T cells and may actually suppress a mixed lymphocyte reaction, suggesting the potential for allogeneic use of hMSCs (K. McIntosh, pers. comm.). The lack of a pronounced immunological response to implanted allogeneic hMSCs and the ability to produce large numbers of cells from a small marrow aspirate open the potential to use donor-derived cells for multiple recipients. To this goal, Osiris Therapeutics has undertaken clinical trials for the use of allogeneic hMSCs to aid engraftment of matched bone marrow or mobilized peripheral blood progenitor cells. Phase I results suggest the matched hMSCs are well tolerated, and ongoing Phase II studies will provide appropriate dosage data. The pivotal Phase III multicenter trial will occur in the near future. Perhaps bone marrow derived hMSCs will be used to heal not only mesodermal tissues but also ectoderm- and endoderm-derived tissues one day.
The epidermis of the mammals forms the outer covering of the skin and compromises both interfollicular epidermis and the edinaxal structures, such as hairs and sebaceous glands (Odlands 1991). The major cell type in the epidermis is an epithelial cells which is known as keratinocytes. Interfollicular epidermis is made up of multiple layer of keratinocytes. The basal layer of cells, attached to the underlying basement membrane, contains keratinocytes that are capable of dividing, and cells that leave the basal layer undergo a process of terminal differentiation as they move toward the surface of the skin. The end point of this pathway is an anucleate cell, called a squame, which is filled with insoluble, transglutaminase-crosslinked protein and provides an effective barrier between the environment and the underlying living layers of the skin. The basal layer of interfollicular keratinocytes is continuous with the basal layer of keratinocytes that form the hair follicles and sebaceous glands; once again, the end point of terminal differentiation is a dead, highly specialized cell, forming the hair shaft or the lipid-filled sebocytes. If stem cells are defined as cells with the capacity for unlimited selfrenewal and also the ability to generate daughter cells that undergo terminal differentiation (Hall and Watt 1989; Watt 1998; Watt and Hogan 2000), then the epidermis is one of the tissues in which a stem cell compartment must be present. Throughout adult life there is a requirement for the production of new interfollicular keratinocytes to replace the squames that are continually being shed from the surface of the skin, and there is also a need to produce new hairs to replace those lost at the end of each hair growth cycle. It seems likely that there is a single, pluripotential, stem cell compartment in the epidermis and that the differentiation pathway selected by stem cell progeny is determined by the microenvironment in which they find themselves (Watt and Hogan 2000).
Keratinocytes have not featured in the numerous recent accounts of the plasticity of stem cells in a variety of tissues. Two observations suggest, however, that some plasticity exists. First of all, the process of keratinocyte terminal differentiation can be reversed by introduction of a viral oncogene (Barrandon et al. 1989). Second, metaplasia of epithelial cells, including keratinocytes, is not uncommon: This is the formation of one differentiated cell type from another in postnatal life, such as the formation of ectopic intestinal epithelium in the stomach or endocervical epithelium in the vagina (Slack 2000). To form epidermal comparable of the patient's own skin, the keratinocytes are cultured and it provides the tissue for the autologous grafting, bypassing the problem of rejection. Presently, it is being studied in clinical trials as an alternative to surgical grafts used for venous ulcers and burn victims.
Brain cell transplantation:
Neural stem cells are the only cells that are thought to be strictly embryonic but many studies proved this incorrect. So the major focus of current research is the localisation and identification of the neural cells. Replacement therapy is also used for the treatment of the brain diseases. Brain diseases such as Alzheimer's disease and parkinson's disease, stroke, spinal cord injury which can be treated by replenishing damaged tissue and to keep the unneeded muscle from moving it brings back the specialized brain cells.
In an impressive demonstration of pluripotentiality, Frisen and colleagues (Clarke et al. 2000) injected adult neural stem cells into chick embryos and mouse blastocysts and showed that neural stem cells contributed to ectodermal, endodermal, and mesodermal tissue. Contributions to tissue were large and occasionally comprised as much as 30% of the entire organ. These data suggest that neural stem cells are capable of contributing to multiple tissues, and under appropriate conditions this contribution may be very large. Thus, the term neural may be too restrictive.
In Parkinson's disease, there is a loss of the cells which are produces the neurotransmitter dopamine. For the Parkinson disease, after the study of the first double blind of the fetal cell transplants it was reported that there is a release and survival of the dopamine transplanted cells and the clinical symptoms are functionally improved. Side effects are developed when there was a over sensitization of dopamine. At the cellular level the success of the experiment is significant but the at the time the side effects are anticipated. With the use of the human fetal tissue over 250 patients have already been transplanted.
Treatment for Diabetes:
Insulin-dependent, or type I, diabetes mellitus (IDDM) is a devastating disease in which affected individuals depend on daily injections of exogenous insulin for regulation of glucose homeostasis and survival. The lifetime dependency on insulin invariably leads to a variety of debilitating complications that threaten quality of life and significantly shorten life expectancy of IDDM patients. Knowledge regarding pancreatic stem cells has grown dramatically in recent years, but continued progress is still hampered by the lack of in vitro and in vivo assay systems for stem cell activity and function. The field of pancreatic islet cell ontogeny enjoyed comparative solitude until the fascinating discovery that factors regulating insulin transcription were required for the differentiation of the mature pancreas. This and related discoveries have fuelled the rapid expansion of the pancreas ontogeny field, the discovery of a variety of potential islet stem cells, and new theories on the ontogeny of mature islet cells. Indeed, several proteins associated with pancreatic stem cells have been defined, and studies have shown that a number of transcription factors are important in pancreas differentiation.
The identification of islet stem cells, the development of new antigenic markers for these cells, and the establishment of an assay system to monitor stem cell activity will be of critical importance in advancing our knowledge of pancreatic islet stem cell ontogeny. Such knowledge could enable critical advances in the development of new therapies for IDDM, a debilitating disease that severely compromises pancreatic function in affected individuals. For example, new pancreatic islet cells could be differentiated from pancreatic stem cells in vitro for ß-cell replacement therapy. In addition, given sufficient knowledge of pancreatic stem cells and the factors that influence their growth and differentiation, it is possible that administration of the appropriate growth factors could allow the induction of new islet cells directly within IDDM patients. The exciting progress and ongoing research in the pancreatic stem cell field are critical if we are to find an eventual means for achieving these important goals.
Blood disease treatment:
B lymphocytes, T lymphocytes, and natural killer (NK) cells (cells of the lymphoid lineages ) and erythrocytes, megakaryocytes, platelets, granulocytes, monocytes, macrophages, osteoclasts, and dendritic cells (cells of the erythroid/myeloid lineages) are all descendants of a pluripotent hematopoietic stem cell (pHSC). In fact, transplantation of a single pHSC can reconstitute a lethally irradiated host with all these lineages of cells. The differentiated cells of the erythroid/myeloid and lymphoid lineages, with the exception of memory B and T cells, turn over rapidly, with half-lives between days and weeks. Therefore, in order to maintain the pools of hematopoietic cells in an individual, these cells have to be continuously generated throughout life by cell division and differentiation from stem cells.
The adult hemapoietic cells are used for years for the treatment of the diseases such as anemia, sickle cell, leukemia and other immunodeficiency.
Fate mapping stem cells:
The definition of fate mapping should be restricted to determining a "normal" fate for a defined stem cell, i.e., determination of the fate that a stem cell would be expected to have in its normal environment under the regulatory influences of homeostasis. It is apparent that the reductionism inherent in in vitro systems is fundamentally flawed for fate mapping applications and could misrepresent the normal fate of a stem cell. For example, if long-term bone marrow cultures were used for fate mapping of hematopoietic stem cells (HSC), a skewed, predominantly myelopoietic
Perspective of HSC fate would be assumed.
Potential new 'Twist' in the breast cancer detection:
Scientists at Johns Hopkins have shown that protein made by a gene called 'Twist' may be proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells when they are working with mice. So these breast cancer stem cells have fundamental implication for the early identification, their treatment and preventation. Some tumor cells are also killed some cancer treatments while the rare cancer treatment cell are sparing.
Cholesterol lowering drugs also may protect stem cell which is used for transplant patient from a deadly complication of life saving cancer therapy.
It is also the one of the application of the stem cells.
The field of stem cell research has attracted many investigators in the past several years. Progress in embryology, haematology, neurobiology, and skeletal biology, among many other disciplines, has cantered on the isolation and characterization of stem cells. The approaching completion of the sequencing of the human genome has lent further impetus to exploring how gene expression in stem cells relates to their dual functions of self-renewal and differentiation.
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