Module 3: Are Human iPS Cells Equivalent to hESC?

Human iPS cells staining positively for OCT4

Module Leader Dr Andrew Laslett
Host Organisation CSIRO

Module description

The objective of this module is to investigate critical differences between human iPS cell lines, generated using distinct methodologies, and hESC. IPS cells are being touted as the ‘ethical’ alternative to hESC for the development of cell-based therapies however significant questions remain as to their long term stability, their equivalence to hESC at all levels and ultimately their safety. The hypothesis to be tested in this application is that human iPS cells produced by different means  vary in equivalency to hESC in terms of their ability to be maintained as stable cell lines under a variety of conditions. Outcomes from this module will include the identification of best practice methodologies for the generation of human iPS cell lines and the identification of risks associated with reprogramming.

Aims

The overall aim of this module is to perform detailed characterisation and comparison of multiple human iPS cell lines with each other and with hESC to determine whether iPS cells are equivalent to hESC. Specifically the following research questions will be addressed:

Question 1: Are hESC and iPS cell lines equivalent by immunotranscriptional and epigenomic profiling?
Question 2: Do hESC and iPS cell lines behave identically when functionally assessed?
Question 3: Are human iPS cell lines as stable as hESC after prolonged culture?
  

Module Leader biography

Andrew and his team joined CSIRO Molecular Health Technologies in August 2009 and they remain based at the Australian Stem Cell Centre (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 of 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.

Contact details

 E-mail  andrew.laslett@csiro.au 
 Phone  +61 3 9271 1133

Selected publications

  1. Laslett AL, Filipczyk A & Pera MF (2003). Characterization and Culture of Human Embryonic Stem Cells. Trends In Cardiovascular Medicine 13(7):295-301.
  2. Martin F. Pera, Adam Filipczyk, Susan M. Hawes, and Andrew L. Laslett (2003) Isolation, characterization, and differentiation of human embryonic stem cells. Methods in Enzymology 365: 429-46.
  3. Martin F. Pera, Andrew Laslett, Susan M. Hawes, Irene Tellis, Karen Koh, and Linh Nguyen. (2006) Isolation and characterization of human embryonic stem cells.  In Embryonic stem cells:  a practical approach.  Edited by Elena Notarianni and Martin J. Evans. Oxford University Press, p238-259.
  4. Herszfeld D, Wolvetang E, Filipczyk A, Langton –Bunker E, Koh K, Nguyen L, Tellis I, Michalska A, Laslett AL, Reubinoff BE, Houssami S, Looijenga LH and Pera MF (2006) CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nature Biotechnology 24(3):351-7.  
  5. Andrew L. Laslett, Sean Grimmond, Brooke Gardiner, Lincon Stamp, Adelia Lin, Susan M. Hawes, Sam Wormald, David Nikolic-Paterson, David Haylock, and Martin F. Pera (2007)  Transcriptional Analysis of Early Lineage Commitment In Human Embryonic Stem Cells.  BMC Developmental Biology Mar 2;7:12.
  6. Adam A. Filipczyk, Andrew L. Laslett, Christine Mummery & Martin F. Pera. (2007) Differentiation is Coupled to Changes in the Cell Cycle Regulatory Apparatus of Human Embryonic Stem Cells. Stem Cell Research 1:1; 45-60.
  7. Andrew L. Laslett, Adelia Lin and Martin F. Pera (2007) Characterization and differentiation of human embryonic stem cells. In: Embryonic Stem Cells edited by .JR.Masters et al, Springer, p27–40.
  8. Andrew L. Laslett, Andrew Fryga and Martin F. Pera (2007) Flow cytometric analysis of human embryonic stem cells. In: Human Stem Cell Manual:  A Laboratory Guide, edited by Jeanne F. Loring, Elsevier, p96-107.
  9. Lina Gubhaju, Andrew Laslett, John F. Bertram, Anthony Zulli, Jane M Black (2008) Immunohistochemical localisation of TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney. Histochemistry and Cell Biology 129(5):651-7.
  10. Kolle, G. Ho, SHM., Zhou, Q, Chy, H.S., Krishnan, K, Cloonan, N, Bertoncello, I, Laslett, A.L. and Grimmond, S.M.  Identification of human embryonic stem cell surface markers by combined membrane-polysome translation state array analysis and immunotranscriptional profiling. Stem Cells (in Press, July 2009)