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UCSD BGGN 231 - Stem Cell Primer

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Stem Cell Primer**Adapted from materials from the ISSCR web site.(http://www.isscr.org/public/index.htm)Embryonic Stem CellsThe most flexible type of stem cell is the embryonic stem cell. This cell is distinct from the stem cells found within the adult body, because it comes from cells found in the 5-6 days old embryo, called the blastocyst. Embryonic stem cells are made from left-over blastocysts that have developed from fertilized eggs produced by assisted reproduction technologies, such as in vitro fertilization. These left-over blastocysts, if not donated to another couple or used for research, are usually discarded. Once embryonic stem cells have been established in culture, large numbers of cells can be grown for a long time, without losing the stem cell character. The most remarkable feature of embryonic stem cells is their ability to generate all functional adult cell types. Culture methods have been developed to turn embryonic stem cells into brain, heart, muscle cells, blood cells, blood vessels, skin, pancreatic islet cells and bone cells.It is therefore anticipated that research with embryonic stem cells will help produce cells and tissue for replacement therapies for treating disorders such as Parkinson's disease, heart attacks, blood disorders and diabetes. Adult Stem CellsAdult stem cells are stem cells that come from different parts of the body and, depending on where they are from, have different properties. They exist in several different tissues including bone marrow, blood and the brain. Although a wealth of information on adult stem cells has already been collected, scientists still do not understand their specific properties well. It had for example been suggested that adult stem cells from one organ can turn into cells of another organ. Recent rigorous studies have however not proven such claims.Hematopoietic stem cells, the blood forming stem cells, are adult stem cells found mainly in the bone marrow and they provide the blood cells required for daily blood turnover and for fighting infections. Compared to adult stem cells from other tissues, hematopoietic stem cells are easy to obtain and have been studied by scientists for many years. They were the first stem cells to be used successfully in blood disorder therapies. More recently, their use in treatment of breast cancer and coronary artery diseases is also being explored.-1-Potential of human embryonic stem cells. Embryonic stem cell colonies shown in the middle could potentially one day be grown in culture to the illustrated organs and more. While to date many cell types have been grown from embryonic stem cells, culture conditions need more refinement before entire organs could possibly be grown in culture.Illustration of the different cells within the blood that are generated by the hematopoietic stem cells. In murine transplantation experiments it has been demonstrated that one single hematopoietic stem cell can reconstitute an entire mouse which had its blood wiped out entirely, including its own hematopoietic stem cells. This mouse can then live healthily with the new blood generated by one single stem cell.Mesenchymal stem cells are another well-characterized population of adult stem cells. These cells, also found in the bone marrow, can form a variety of cell in the laboratory, including fat cells, cartilage, bone, tendon and ligaments, muscles cells, skin cells and even nerve cells.Unlike most other human adult stem cells, mesenchymal stem cells can be obtained in quantities appropriate for clinical applications, making them good candidates for use in tissue repair. Perhaps one of the important considerations for human applications is that mesenchymal stem cells can be obtained from a small bone marrow sample from a given patient, expanded in culture, and given back to the patient. This would avoid the problems associated with immune rejection of foreign transplanted cells or tissues. Umbilical cord blood stem cells can be obtained from the umbilical cord immediately after birth. Like bone marrow, umbilical cord blood is another rich source of hematopoietic stem cells. These hematopoietic stem cells are usually referred to as neonatal stem cells and are less mature than the hematopoietic stem cells found in the bone marrow of adults. The advantages of using cord blood as a source of stem cells are that umbilical cord blood is easily obtained and is abundant; thousands of babies are born each day and, until recently, umbilical cord blood was discarded after birth. Now, cord blood is collected and stored by public or private cord blood banks. Cord blood has recently emerged as an alternative source of hematopoietic stem cellsfor the treatment of leukemia and other blood disorders. However, there is a limited number of stem cells in any given cord which prevents its generalized use for the treatment of blood disorders in adults. The use of umbilical cord blood stem cells for other uses, such as organ and tissue repair, is under also investigation.Self-Renewal and Stem Cells Expansion for TherapyA stem cell is defined as a cell that can renew itself indefinitely, while producing cell progeny that mature into more specialized, organ-specific cells. To accomplish this task, the stem cell has to divide continuously. These divisions are asymmetric. One of the two daughter cells retains the stem cell characteristics, while the other is destined for a limited number of future divisions and will produce the more organ-specific cells. Although scientists are learning more and more about this complicated cell division mechanism, they are still a long way from understanding it.For successful therapeutic application most of the adult stem cells isolated from the body will have to be amplified in culture. While the embryonic stem cell can be coaxed to amplify in culture without losing its capabilities, adult stem cells (with exception of the mesenchymalstem cell) can not be amplified in culture to meaningful cell numbers. Only once scientists-2 -MESENCHYMAL STEM CELLMyotube(Muscle)TendonLigamentAdipocyte(Fat)Dermal Cell(Skin)CartilageBoneMarrow StromaMESENCHYMAL STEM CELLMyotube(Muscle)TendonLigamentAdipocyte(Fat)Dermal Cell(Skin)CartilageBoneMarrow StromaIllustration of the different cell types generated by human mesenchymal stem cells. Stem Cell Division. The stem cell divides asymmetrically, generating one cell that repeats the feat indefinitely, and one cell that continues to divide symmetrically,


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