Stem Cells General Concepts By Syed Tahir Abbas Shah Outline Introduction History Types of Stem Cells Regulation of Stem Cells Application of Stem Cells Ethical Issues Conclusion Introduction-Definition Stem cells— Cells with the ability to divide for indefinite periods in culture and to give rise to specialized cells. Introduction-Properties Capable of dividing and renewing themselves for long periods Unspecialized Can give rise to specialized cell types Introduction-Stem cell strategies Formation of blood cells from Stem Cell Stem Cell Research History 1956-First successful bone marrow transplant between relatives is completed 1968-In vitro fertilization begins 1973-First bone marrow transplant between unrelated people is successful 1978-Blood (adult) stem cells are discovered in umbilical cord blood 1981-Mouse embryonic stem cells are first isolated http://www.stemcellresearchformichigan.com/faq-history.php Stem Cell Research History 1995-University of Wisconsin isolates embryonic stem cells in primates 1998-University of Wisconsin researchers, led by Dr. James Thomson, isolate first human embryonic stem cells 2002-Pancreatic cells derived from mouse embryonic stem cells cure diabetes in mice http://www.stemcellresearchformichigan.com/faq-history.php Stem Cell Research History 2004-South Korean researchers claim to have cloned human embryo. Research is later discredited as untrue. Nerve cells lost in Parkinson’s disease are produced from human embryonic stem cells California becomes first state to provide own funding for embryonic stem cell research 2005-Human neural cells injected into mice help reverse paralysis http://www.stemcellresearchformichigan.com/faq-history.php Stem Cell Research History 2006-Embryonic stem cells first grown without animal products in the feeder layer of the culture 2007-Teams of researchers in Wisconsin and Japan modify adult skin cells into induced Pluripotent Stem (iPS) cells which behave like embryonic stem cells by using viruses to introduce four genetic factors that cause the change http://www.stemcellresearchformichigan.com/faq-history.php Stem Cell Research History 2008-Various researchers announce success with creating iPS cells using fewer viruses and genes 2009-FDA approves world's first clinical trial using human embryonic stem cell-based therapies for California company to test a treatment for spinal cord injury NIH guidelines http://www.stemcellresearchformichigan.com/faq-history.php Stem Cell Types (Sources) Embryonic Stem Cells Fetal Stem Cells Adult Stem Cells Amniotic Stem Cells Induced pluripotent Stem Cells Embryonic vs Adult Stem Cells Induced Pluripotent Stem Cells Stem Cell Types (Potency) Totipotent(omnipotent)- can differentiate into embryonic and extraembryonic cell types Pluripotent- can differentiate into nearly all cells i.e. cells derived from any of the three germ layers. Multipotent- can differentiate into a number of cells, but only those of a closely related family of cells. Oligopotent- stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells. Unipotent- cells can produce only one cell type, their own, but have the property of self-renewal (e.g. muscle stem cells) Origin of Human Pluripotent Cells Stem Cell Types (Potency/Source) Stem Cell Regulation- Niche Stem Cell Regulation- Niche Stem Cell Regulation- Epigenetic Regulation of long-term self renewal Mouse ESCs LIF (Smith et al., Nature, 1988) BMP (or serum) (Ying et al, Cell, 2003) 3i (Ying et al, Nature, 2008) (Buehr et al, Cell, 2008) LIF and BMP act on downstream differentiation signals of MAPK He S et al. 2009. Annu Rev Cell Dev Biol; Dr. Fei Wang Stem Cell Regulation- MicroRNAs Cancer Stem Cells Application of Stem Cells Differentiation of embryonic stem cells Strategies to repair heart muscle with adult stem cells Embryonic Stem Cells and Therapeutic Cloning In therapeutic cloning, a nucleus from an adult human cell would be transferred to an enucleated egg. The resulting embryo could produce differentiated cells for transplantation therapy. This would bypass the problem of tissue rejection. Embryonic Stem Cells and Therapeutic Cloning Ethical Issues Summary Properties- Self renewal, unspecialized, give rise to specialized cells. Types- Totipotent, pluripotent, unipotent Regulation- Niche, miRNA, epigenetic Application- Therapeutic cloning, treatment of a variety of diseases. Ethical Issues- Donation of biological material, hESC, Clinical Trails References Donovan, P. J., & Gearhart, J. (2001). The end of the beginning for pluripotent stem cells. Nature, 414(6859), 92-97. doi:10.1038/35102154 Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126(4), 677-689. doi:10.1016/j.cell.2006.06.044 Jones, D. L., & Wagers, A. J. (2008). No place like home: Anatomy and function of the stem cell niche. Nature Reviews.Molecular Cell Biology, 9(1), 11-21. doi:10.1038/nrm2319 Gangaraju, V. K., & Lin, H. (2009). MicroRNAs: Key regulators of stem cells. Nature Reviews.Molecular Cell Biology, 10(2), 116-125. doi:10.1038/nrm2621 http://www.stemcellresearchformichigan.com/faq-history.php http://stemcells.nih.gov/info/ http://en.wikipedia.org/wiki/File:Stem_cell_treatments.svg