Introduction to stem cellsStem cell Community Forum

Raymond Wong, PhDNeuroregeneration Research Unit, CERA

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

What is a stem cell?

• Can self-renew: reproduce itself

• Can differentiate: give rise to specialized cells

Handbook of stem cells, Elsevier, R. Lanza, EditorFrom Stem Cell Teacher Kit, 2010(Australian Stem Cell Centre)

Different types of stem cells: Multipotent vs pluripotent

From Stem Cell Research FoundationFrom Sarah Wray

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

• ‘Switch on’ several genes => ‘add’ several proteins in the cells

Adult fibroblasts Reprogramming Human iPS cellsSkin biopsy

Hair Keratinocytes

Nanog

Oct4

Reprogramming to make iPS cells

Patient-specificstem cells(iPS cells)

Eye cells(or any cell type)

Patient

Cell replacement therapy

DifferentiationReprogramming

Drug screeningSomatic cells

Disease modelling

Potentials of iPS cells:

• 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)

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:

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’

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

Neuroregeneration Unit, 2013

Acknowledgements: