17) Stem Cells Summary 9744 2019

The Cell and Biomolecules of Life (9744) Stem Cells 2019 Prepared by: Mrs. Selvamani Nair and Mr Low Chor Meng Raffles Institution 1 Stems Cells a) are unspecialized/undifferentiated i.e. they do not have any tissue-specific structure for it to perform a particular function b) are able to differentiate to produce specialised cells upon receiving appropriate molecular signals (e.g. hormones, growth factors) c) undergo extensive proliferation and self-renewal i.e. they can divide many times by mitosis, with the daughter cells possessing the same developmental and replicative potential as the parent cell d) can undergo 1) symmetrical division  produces 2 identical daughter stem cells to ensure a constant pool of stem cells 2) asymmetrical divisionproduces a) 1 daughter stem cell  to ensure a constant pool of stem cells & b) 1 progenitor cell to replace a population of specialised cells in a specific tissue that died occurs in the presence of appropriate molecular signals e) can be 1) totipotent  can differentiate into all of the cell types that make up an entire organism including the extraembryonic tissue e.g. the placenta  e.g. fertilised egg to 8 cell stage (These cells are zygotic stem cells.) 2) pluripotent  can differentiate into all of the cell types that make up an organism except the extraembryonic tissue such as the placenta  e.g. inner cell mass of blastocyst (The cells in the inner cell mass are embryonic stem cells.) 3) multipotent  can develop into only a limited and related range of cell types and tissues in an organism  e.g. haematopoietic stem cells, which are found in the bone marrow & give rise to all of the cells found in the blood, including red blood cells, white blood cells, and platelets. Haematopoietic stem cells are adult stem cells. They are also found in babies.) Note: 1) Stem cells can differentiate into different cell types due to the presence of molecular signals that cause differential switching on of genes. 2) A progenitor cell is an early descendent of a stem cell that can only differentiate. It cannot renew itself. e.g. lymphoid progenitor cells gives rise to B cells, T cells and natural killer cells while myeloid progenitor cells give rise to red blood cells, monocytes, platelet producing cells, neutrophils, basophils and eosinophils 3) Stems cells can continue to divide mitotically as they can express their telomerase gene which lengthens the telomeres of their chromosomes and hence prevents them from reaching critical length and hence prevents the cell from undergoing apoptosis. Discuss the ethical implications of the application of stem cells in research and medical applications and how induced plurip otent stem cells (iPSCs) overcome some of these issues. (procedural details of how iPSCs are formed are not required) Ethical implications of the use of stem cells in therapy Argument against using embryonic stem cells Argument for using embryonic stem cells Some believe that the embryo has the status of a human being as it has the potential to become one. Embryonic stem cell research is tantamount to murder. Some object to extracting stem cells from an embryo to make replacement body cells is treating the embryo as just a source of spare parts. Claims of the benefits of embryonic stem cell research are over-rated as there are few (if any) examples of success in medical applications Adult stem cell treatment is established, have produced some results and there are fewer ethical issues involved. Thus adult s tem cell research may be able to make greater advances if more money and resources were channeled into it instead of embryonic stem cell research. Current benign applications may lead to abuse in the future . Once human status is denied to embryos, this precedent may extend to other categories of human beings such as the profoundly disabled or the elderly infirm. Possibility of unforeseen consequences in treated patients such as possible risks of tumor formation, immunological reactions, unexpected behavior of the cells, and unknown long-term health effects. As embryonic stem cell research is expensive, funds can be channeled to treat other more treatable diseases. For donors of eggs, embryos or tissues, there are issues of informed consent, understanding of research aims and privacy. Embryos are not equivalent to human life: Embryos are not conscious, cannot feel and cannot survive outside the womb. Blastocysts are a cluster of human cells that have not differentiated into distinct organ tissue, making cells of the inner cell mass no more "human" than a skin cell. Some believe life only begins when the heartbeat develops (during the fifth week of pr egnancy) or when the brain begins developing (at 54 days after conception). Embryonic stem cells can potentially treat a wide range of diseases as they have the potential to grow indefinitely in a laboratory environment and can differentiate into almost all types of bodily tissue. It is unethical not to use established protocols on embryonic stem cell research to further embryonic stem cell research to help relieve human suffering. There is legislation on the period when ES cells can be extracted. eg: Current UK legislation does not allow use of embryos that are more than 14 days old . In fact, ES cells are obtained earlier from blastocyst (between 3-8 days after fertilization). More than a third of zygotes do not normally implant in the uterus. Thus, far more embryos are lost due to chance than are proposed to be used for embryonic stem cell research. Surplus embryos created via in vitro fertility treatments are destroyed, or stored long past their viable storage life. These can be used for creating new stem cell lines for research which would otherwise be destroyed. fertilized egg  2 cell stage  4 cell stage  8 cell stage   blastocyst     baby trophoblast inner cell mass (pluripotent embryonic stem cells) haematopoietic stem cells in bone marrow are multipotent adult stem cells totipotent zygotic stem cells blastocyst cavity

The Cell and Biomolecules of Life (9744) Stem Cells 2019 Prepared by: Mrs. Selvamani Nair and Mr Low Chor Meng Raffles Institution 2 Potential solution to overcome some of these issues Induced pluripotent stem cells (iPSCs) Induced pluripotent stem cells are pluripotent stem cells that can be generated directly from adult somatic cells (e.g. skin cells) Adult somatic cells are not totipotent, pluripotent or multipotent . The non -pluripotent cell is therefore induced to become pluripotent. The iPSC technology was pioneered by Shinya Yamanaka’s lab in 2006 that the introduction of four specific genes encoding transcription factors could ‘reprogramme’ some specialised cells to become pluripotent so that they lose their specialised functions and behave in virtually the same way as embryonic stem cell. Advantages of iPSCs Possible problems of iPSCs  Since iPSCs can be obtained directly from adult tissues , it does not generate or destroy any human embryos.  Adult tissue (e.