1. Introduction to stem cells Stem cell Community Forum Raymond Wong, PhD Neuroregeneration Research Unit, CERA

2. What is a cell? An organism’s basic unit of structure & function All living things are made of cells Cells contain information that is inherited (DNA/genes) Levels of organisation: – organism, organs, tissues, cells, DNA=> proteins

3. What is a stem cell? Can self-renew: reproduce itself Can differentiate: give rise to specialized cells Handbook of stem cells, Elsevier, R. Lanza, Editor From Stem Cell Teacher Kit, 2010 (Australian Stem Cell Centre)

4. Different types of stem cells: Multipotent vs pluripotent From Stem Cell Research FoundationFrom Sarah Wray

5. Pluripotent stem cells ‘Reprogramming’ iPS cells Can proliferate indefinitely in the lab: unlimited cell source Pluripotent: can give rise to any cells type in the body adapted from P. Donovan

6. ‘Switch on’ several genes => ‘add’ several proteins in the cells Adult fibroblasts Reprogramming Human iPS cells Skin biopsy HairKeratinocytes Nanog Oct4 Reprogramming to make iPS cells

7. Patient-specific stem cells (iPS cells) Eye cells (or any cell type) Patient Cell replacement therapy Differentiation Reprogramming Drug screening Somatic cells Disease modelling Potentials of iPS cells:

8. Inherited disease affecting ~ 1 in 30000 individuals, predominantly young males Central vision loss occurs usually around teenage to early twenties Mutations in mitochondria cause bioenergetics dysfunction Characterized by loss of retinal ganglion cells (RGCs), cells that form the optic nerve Precise mechanism of how RGCs die is not known Currently no approved treatment for LHON patients No clinical relevant model to study LHON disease Case study: Leber’s hereditary optic neuropathy (LHON) Designed by Brian Ashton, 20 yrs old LHON patient (http://thegenetichouse.wordpress.com)http://thegenetichouse.wordpress.com

9. Disease modelling Extremely difficult to obtain RGC samples from living patient to study LHON disease Currently no RGC cell lines available Potentials of iPS cells” – ‘Disease-in-a-dish’: understand how RGC loss occurs in LHON, which is crucial to developing new treatment Patient-specific iPS cells Retinal ganglion cells Study the disease mechanism:

10. Drug screening Current cost of drug discovery is very expensive and takes a long time – 1.3-5 billion USD development cost, often takes >10 years ~1-5% success rate for experimental drugs to make it to the clinic No approved treatment in the case of LHON Potentials of iPS cells: – Fast-track the process of drug discovery and testing with clinical relevant model – ‘Personalised medicine’

11. Cell therapy Immuno-rejection with transplantation Cell therapy is especially helpful in diseases where affected cells are ‘damage beyond repair’ The need for animal experiment before clinical trial in patients Potential of iPS cells in LHON: – Replace damaged RGCs for restore vision – Unlimited source of cells – Autologous transplantation = minimal risk of graft rejection

12. Neuroregeneration Unit, CERA Dr Alice Pebáy Ms Katie Gill Ms Grace Lidgerwood Dr Sandy Hung Dr Kathryn Davidson Ms Alison Conquest Ms Tejal Kulkarni Mr Duncan Crombie Ms Lerna Jurdukian Funding Cranbourne Foundation Brookhoff Foundation Ophthalmic Research Institute of Australia University of Melbourne ECR grant Neuroregeneration Unit, 2013 Acknowledgements: