ANAT 2341 Embryology Lecture 18 Stem Cells
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1 ANAT 2341 Embryology Lecture 18 Stem Cells 29 September 2010 Dr Antonio Lee Neuromuscular & Regenera<ve Medicine Unit School of Medical Sciences, UNSW Outline What are Stem Cells? Totipotency - Pluripotency - Multipotency What are different sources of Stem Cells? Embryonic vs Adult Pros and Cons for each type of stem cell? What makes Stem Cells, Stem Cells? Self-Renewal & Differentiation What can Stem Cells be used for? Therapeutic Applications for Stem Cells Copyright Disclaimer: This lecture notes contain images and illustrations adopted from Regenerative Medicine 2006 with subsequent updated chapters published by National Institute of Health and Molecular Biology of the Cell (4th Ed) published by Garland Science.
2 Stem Cells in the News What is a Stem Cell? - Pluripotency 1 Cell (Zygote - fertilised egg) 6,000,000,000 cells (230 different cell types)
3 Where does it all begin? - Human Where does it all begin? - Mouse
4 Totipotency vs Pluripotency Development of Primordial Germ Cells
5 What are Different Types of Stem Cells? 1. Embryonic Stem (ES) Cells 2. Embryonic Germ Cells 3. Adult Stem Cells 4. Umbilical Cord-Blood Stem Cells Plus 1. Somatic Cell Nuclear Transfer (SCNT) 2. Induced-Pluripotent Stem (ips) Cells 1. Embryonic Stem (ES) Cells 1. Pluripotent - can generate any cell type in the body. 2. From 5-7 day-old blastocyst - ICM. 3. Can be cultured as cell lines or frozen for future use. 4. In Australia, plenty of embryos are donated from IVF treatments. 5. Ethical issues?
6 2. Embryonic Germ Cells (EGCs) 1. Primordial germ cells (PGCs) destined to become gametes (oocytes / sperm cells) 2. From 5-7 week-old embryos developing into fetus. 3. EGC-lines share many properties with ES cells. 4. But in vitro, PGCs show spontaneous differentiation, thus limited in isolation of pure clonal lines. 3. Adult (Somatic) Stem Cells 1. More specialised than embryonic stem cells. 2. Found in the majority of tissues & organs (for maintenance & repair throughout life-span). 3. Have restricted ability to produce different cell types (multipotent not pluripotent). 4. Identification/isolation can be difficult. 5. Only small numbers may be present requiring expansion ex vivo. 6. More adult stem cell types are being discovered from variety of tissues with plasticity - ability to form cell type of a completely different tissue. 7. Autologous (one s own) use can avoid immune-rejection problems in following transplantations. 8. Ethical issues?
7 3. Adult (Somatic) Stem Cells - Bone (Marrow) 1. Haematopoietic Stem Cells for Blood Cells 2. Stromal Stem Cells for other Mesodermal Tissues 3. Adult (Somatic) Stem Cells - Plasticity? 1. Neural Stem Cells for Blood. 2. Bone-Marrow Stem Cells for Liver, Skin and Neurons. 3. Blood Vessel Stem Cells for Fat and Muscles.
8 4. Umbilical Cord Blood Stem Cells 1. Adult Stem Cells collected from a newborn baby shortly after birth. 2. Can generate all blood cell types including immune system. 3. Potential to generate other tissue types is currently being explored. 4. Can be stored (at cord-blood bank) for future use: matched-siblings, matched but unrelated-individual or autologous-use. 5. Saviour Siblings - using donor baby s cord blood to treat a matched ill sibling. 6. Ethical issues? 5. Somatic Cell Nuclear Transfer (SCNT) - Therapeutic Cloning 1. Nucleus of oocyte is removed and replaced with foreign nucleus from any somatic cell that is reprogrammed in the environment of the egg. 2. Artificial activation of egg and 5-7 days in culture allows development of ES cell-like, SCNT pluripotent stem-cell line. 3. Allows patient-specific cell therapies avoiding immune-rejections following transplantation. 4. Normal Zygote (fertilised egg) vs SCNT-derived egg - Dolly died prematurely with signs of arthritis and lung infection. 5. Reproductive Cloning - Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research Amendment Act 2006 (Australia). 6. Ethical issues?
9 6. Induced Pluripotent Stem Cells (ipscs) 1. Mature somatic cells were genetically engineered by virus to achieve pluripotent, ES-like state (Nov 2007). 2. Forced expression of genes (including Oct3/4 and SOX family) in adult mouse/human cells led to a reprogramming into pluripotent status. 3. Rapid development of strategies for gene delivery (non-integrating viruses, chemicals and small molecules) to prevent permanent / harmful changes. 4. Allows patient-specific cell therapies avoiding immune-rejections following transplantation. 5. Possible clinical use may be distant due to concerns on genetic stability. 6. Ethical issues? Embryonic vs Adult Stem Cells - Pros & Cons Embryonic Stem (ES) Cells Advantages Pluripotency - ability to differentiate into any cell type. Immortal - one cell can supply endless amounts of cells. Easily available - human embryos from fertility clinics. Disadvantages Unstable - difficult to control differentiation into specific cell type. Immunogenic - potential immunerejection when transplanted into patients. Teratomas - tumor composed of tissues from 3 embryonic germ layers. Ethical Controversy - unethical for those who believes that life begins at conception.
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