Wet Lab. Cellular Replacement Therapy And Stem Cell Research - Essay Example

?WET LAB Part The discovery and isolation of stem cells proved to be a in the history of molecular biology, and the medical sciences that they inform. In addition to the obvious advantages of providing a clear model for embryonic development, the discovery of stem cells is also a crucial milestone for genetic manipulation. When embryonic mouse stem cells were isolated more than 25 years ago, the significance of the discovery was soon realized. (Keller, 2005) there are many researchers and hold out hope for cellular replacement therapy arising from stem cell research. Specifically, embryonic stem cells, also known as ES - pluripotent cells are of great concern. They exhibit the potential to differentiate into a variety of final tissue types when they reach their ultimate, fully matured state. Embryonic stem cell lines are usually derived from a blastocyst, or in some cases an earlier stage of embryonic development. The 150 cells which at most comprise the blastocyst are able to differentiate into all types of body tissues. (Stem Cell Information, 2009) Most immediately, a pluripotent stem cell will give rise to the primary germ layers: ectoderm, mesoderm, and endoderm. From these layers, other cells and tissues differentiate but ultimately give rise to all internal organs of the future organism. (Scholer, 2007) Other types of stem cells, further in development also have uses in research and therapy; multipotent stem cells have some flexibility, but usually only within a closely related family of cells, such as cardiac tissue, blood cells. Furthermore, the cells can become Unipotent cells - which are not themselves per se, because they can only produce new cells of the exact same type. On the other end of the spectrum, are totipotent stem cells, these are fertilized zygotes which have the potential to grow into an entire individual, an embryonic stem cell from a blastocyst does not qualify.(Scholer, 2007) Cells can also be classified in terms of progenitor or precursor. Precursors exhibit recognizable traits of the function type they will become, while Progenitors are not outwardly committed to a cell type. (Rabbany et al. 2003) An extensive variety of proteins are responsible for differentiation of which much more research is needed. We are only now discovering the functions of regulatory operators such as Shp2, or transforming growth factor-?, that aids in the expression of chorionic gonadotropin.(Burnham Institute, 2009), (Keller, 2005) A well-studied pathway is the process of hematopoiesis, by which stem cells give rise to various types of blood cells. (Mackey, 2001) There are essentially two branches to the hematopoietic differentiation process: the lineage beginning with a myeloid progenitor, and the lineage stemming from the common lymphoid progenitor. (Parslow et al. 1997) The lymphoid progenitor arises from the multi-potential Hemocytoblast. The lymphoid progenitor differentiates into what are described as T cells. Differentiation is possible into the natural killer cells, CD4 and CD8 types, known as large granular lymphocytes, from which no further cell lines arise. But the lymphoid progenitor can also become the small lymphocyte. This stem cell has the potential to become a T-lymphocyte helper cell, or a B lymphocyte, which can further differentiate into plasma cells from which antibodies are produced. (Leishman et al. 2001), (Obeyesekere et al. 2004) But the hemocytoblast from which these types arise produces more cell types along the myeloid lineage. The myeloid progenitor can differentiate into four other cell lines; erythrocytes – otherwise known as oxygen-carrying red blood cells. Immature erythrocytes can be identified by the presence of a nucleus, since they are similar in size and shape to mature erythrocytes – but a nucleus is ejected from the cell upon reaching full differentiation. (Ownby, 2002) Another differentiation event results in mast cells, whose release of histamine and heparin is responsible for many allergic reactions including anaphylaxis. Myeloid progenitors can also grow larger, and become the megakaryocyte, which themselves release platelets (thrombocytes) which are not a true cell type, but are responsible for blood clotting. Megakaryocyte can be identified by a multi-lobed nucleus, in addition to their greater size relative to most other cells found in blood. Myeloid progenitors still have the potential to become yet another type of stem cell, the myeloblast - which gives rise what are thought of in layman's terms as "White Blood Cells" those types most immediately responsible for fighting infection in the blood. Neutrophils, Eosinophils, and Monocytes (which become Tissue Macrophages, and Basophils which are the rarest blood cell type and possess granules that mediate allergic responses). Neutrophils, with a segmented, pinched off nucleus are the most common type of leukocytes, (white blood cells) and are initially responsible for defense against bacteria. (Dancey et al. 1976) Eosinophils attached to, and will chemically attack internal parasites traveling through the blood. Macrophages are also responsible for attacking bacterial invaders, but are more common body tissues from the lymphoid line, plasma cells produce antibodies which are capable of entrapping viral invaders, as well as performing the complement cascade to inflict membrane damage on bacteria. (Ownsby, 2002), (Parslow et al. 1997) Under normal circumstances, the process of hematopoiesis is largely completed in the bone marrow, which has a variety of arteries and branches allow circulation into the blood. But some cell types, such as mass cells are able to complete will most of their maturation outside of the bone marrow unlike basophils. (Marone, 2000) In order for hematopoiesis to apply the organism with the blood cells and needs on a regular basis, pluripotent stem cells must constantly replicate within the bone marrow. The other population of stem cells will become the myeloid or lymphoid progenitors. The process of hematopoiesis is not entirely understood, the balance of evidence paints a picture in which proteins from other mature cells, not only those in the blood - influence the balance of stem cells within the bone marrow, triggering or vetoing cascades that lead to either a replication or differentiation of a given cell type. T-cells, their ability all other aspects of the immune system have an important signaling role. (Marone, 2000), (Loeffler & Potten, 1990) When examining immature blood cells, protein synthesis is a crucial indicator of future changes to come. Visible chromatin structures in the nuclei of immature cells will be tightly packed when quiescent, and more dispersed during active protein synthesis; a sign that differentiation is in progress. Internally, protein synthesis will be characterized by higher ribosomal content, a highly developed Golgi apparatus, and possibly an acentric nucleus due to the decompaction of the chromatin structures. REFERENCES Burnham Institute (2009, March 18). Protein Is Key To Embryonic Stem Cell Differentiation. ScienceDaily. Retrieved May 2, 2012, from http://www.sciencedaily.com­/releases/2009/03/090318140528.htm Dancey J. et al. 1976. Neutrophil Kinetics in Man . The Journal of Clinical Investigation, 1976 September, 58, 705-715. Keller, G. 2005. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. doi: 10.1101/gad.1303605 Genes & Dev. 2005. 19: 1129-1155. Leishman, A. et al. 2001. T cell Responses Modulated Through Interaction Between CD8AA and the Nonvlassical MHC Class I Molecule, Tl . Science, 2001 November, 294, 1936-1939. Loeffler, M., Potten, C.S. 1990. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt . Development, 1990 December, 110(4), 1001-20. Mackey, M.C. 2001. Cell kinetic status of haematopoietic stem cells. Cell Proliferation. 2001;34:71-83. Marone, G. 2000. Mast cells and Basophils. Academic Press. Harcourt Publishers. Obeyesekere, M.N., Berry, R.W., Spicer, P.P., Korbling, M. 2004. A mathematical model of haemopoiesis as exemplified by CD34 cell mobilization into the peripheral blood. Cell Prolif. 2004 Aug;37(4):279-94. Ownby, C.L. 2002. Hematopoiesis, Histology reference. http://instruction.cvhs.okstate.edu/histology/HistologyReference/hrhemac.htm. Accessed: 5/2/2012. Parslow, T.G., Stites, DP., Terr, A.I, Imboden, J.B. 1997. Medical Immunology (1 ed.). ISBN 0838562787. Rabbany, S., Heissig, B., Hattori, K., Rafii ,S. 2003. Molecular pathways regulating mobilization of marrowderived stem cells for tissue revascularization. Trends Mol Med. 2003 Mar;9(3):109-17. [Abstract] Scholer, H.R, (2007). "The Potential of Stem Cells: An Inventory". In Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner. Humanbiotechnology as Social Challenge. Ashgate Publishing, Ltd. p. 28. ISBN 9780754657552. Stem Cell Information, 2009. [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009 [cited Thursday, May 03, 2012] Available at Read More