In the past eighteen months, a series of discoveries have shown that normal adult cells can be reprogrammed in the laboratory so that they display many of the properties of embryonic stem cells and are capable of dividing and differentiating into the major cell lineages of the body. This ability to convert fully differentiated cells into a highly plastic state that mimics the pluripotent cells of the early embryo was both unexpected and revolutionary.
Although Australian stem cell scientists were not involved in the seminal work, researchers in this country are nevertheless very well-placed to explore the mechanisms involved in reprogramming and in the potential uses of reprogrammed cells to treat human disease. Generation of reprogrammed cells, known as induced pluripotent stem cells (iPS cells), does not involve the use of embryos and the starting material is easily accessible, potentially coming from any cell of the human body. In addition, iPS cells can be patient-specific and therefore potentially overcome the problem of immune rejection in patients. iPS cells can also be used as tools for high throughput drug discovery and screening, as disease models, and for understanding the complexities of reprogramming.
Collaborative Stream 2 is composed of eight specialised modules that will tackle the key problems that must be solved before the clinical potential of iPS cells can be realised. During the next two years, the goals are to:
(i) catalogue and define the molecular events that drive the process of reprogramming (Modules 1-4),
(ii) explore the potential use of reprogrammed adult stem cells to regenerate cardiac tissue (Module 6) and
(iii) test the therapeutic potential of iPS cells in models of human disease (brain, bone and periodontal disorders and diseases; Modules 5, 7-8).
This Collaborative Stream brings together existing Australian expertise to elucidate reprogramming and pluripotency in Victoria, South Australia and Queensland and provides a vehicle for Australia to compete and collaborate internationally in the reprogramming field. Furthermore, this Stream creates a pipeline from discovery to testing to clinical application; has both short and long term commercial potential; interfaces well with the National Stem Cell Facility in Queensland and Victoria; complements the research programs of the three other Collaborative Streams; and advances scientific understanding of a biological process fundamental to development.
Outcomes expected in two years are enhanced efficiency of reprogramming; progress in assessing the safety and stability of iPS cells and progress in disease modelling and repair.
Induced PS cells and methods arising in Stream 2 have a number of points of entry to each of the other Streams. It is expected that Stream 2 will receive input from the other streams in the form of model systems for testing iPS cells, methods for differentiation analysis and surfaces and devices for iPS expansion.
Commercial opportunities exist in the three areas of new biological reagents, iPS cell-based disease models as drug screening platforms and the generation and banking of patient-specific iPS cells.
Stream Leader: A/Professor Ernst Wolvetang
Associate Professor Wolvetang leads the human embryonic stem cell engineering group within the Australian Institute for Bioengineering and Nanotechnology, University of Queensland. Previously, he was head of the Basic Human Embryonic Stem Cell Biology Laboratory at the Australian Stem Cell Centre (ASCC) and Honorary Senior Lecturer in the Department of Anatomy and Cell Biology at Monash University. Between 1997 and 2006, Associate Professor Wolvetang was located at the Centre for Early Human Development in the Institute for Reproduction and Development, Monash University, initially looking at the role that ETS2 plays a role in immune cell destruction, neuronal apoptosis and transcriptional regulation of the amyloid precursor gene.
He then joined the laboratory of Associate Professor Martin Pera (2003-2006) to investigate the role of signalling/gene regulation pathways in the control of growth, differentiation and apoptosis of human embryonic stem cells (hESC) by using retroviral transduction of sh RNA’s and cDNAs. This work culminated in his publication Nature Biotechnology describing the relationship between the expression of CD30, apoptosis and genetic instability in hESC. As a result of this work, Associate Professor Wolvetang is now recognised nationally and internationally for his knowledge on proliferation, apoptosis and genetic stability of hESC.
Deputy Stream Leader: Dr Andrew Laslett
Andrew and his team joined CSIRO Molecular Health Technologies in August 2009 and they remain based at the ASCC in Clayton. Prior to this he was a Senior Scientist and Group Leader of the Human Embryonic Stem Cell Technology Laboratory at the ASCC. Dr Laslett’s research compares human embryonic stem cells to human induced pluripotent stem cells and is focused on exploiting the basic biology of these cell types to create novel tools that enhance pluripotent cell research translation. He leads an independent program as well as having significant national and international collaborations.
In September 2007, Dr Laslett was elected as a Board Member and Director of the Australian Society for Medical Research (ASMR). Dr Laslett’s research is supported by the Australian Stem Cell Centre, the NHMRC, the Victoria California Stem Cell Alliance (Victorian Government and California Institute for Regenerative Medicine) and the NSW/Victorian Government Stem Cell Research Grant Program.