Module 7: Characterisation and Propagation of hES Cell Derived Haemopoietic Precursors

Module Leader	Associate Professor David Haylock
Host Organisation	CSIRO and CRC-Polymers

Module description

The intent of this component of the program is to use complementary approaches to characterise putative haemopoietic stem and progenitor cells derived from human embryonic stem and iPS cells. In these studies, phenotypically analogous populations isolated from human cord blood, bone marrow or mobilised blood will be used for comparison.

Work in this module is based on the primary hypothesis that hES and iPS cell derived human haemopoietic stem and progenitor cells express identical molecular and phenotypic markers to counterpart cells isolated from adult human haemopoietic tissues.  Based on this underpinning hypothesis it is also hypothesised that hES and iPS derived haemopoietic stem cells (HSC) and progenitor cells (HPC) will also exhibit functional responses equivalent to adult counterparts.

Aims

In accord with these hypotheses work conducted in this module will involve the following studies with pluripotent cell derived haemopoietic precursor populations that aim to:

1. Characterise the repertoire of cell surface markers including cytokine and chemokine receptors, cell adhesion molecules, lineage associated markers and activation markers.
2. Examine growth in chemically defined media to assess requirement and responsiveness to haemopoietic growth factors and cytokines.

Module Leader biography

Associate Professor David N Haylock has extensive knowledge and expertise in the biology of human haemopoietic stem and progenitor cells. He made the initial observation that haemopoietic recovery following high dose induction chemotherapy for acute myeloid leukaemia was associated with a dramatic increase in the level of circulating haemopoietic progenitor cells. In collaboration with Drs Juttner and To, he pioneered autologous transplantation with mobilised blood progenitor cells, a technique that has since revolutionised haemopoietic transplantation. During the last decade, Associate Professor Haylock has focused on ex vivo manipulation of haemopoietic stem and progenitor cells for therapeutic purposes.

From 2000-2005, as Head of Experimental Cell Therapy at the Peter MacCallum Cancer Centre, Associate Professor Haylock lead Australia’s first clinical trial with ex vivo expanded CD34+ cells in the setting of repetitive high dose chemotherapy for metastatic breast cancer. He was appointed as the Director of the Major National Research Facility Division of the Australian Stem Cell Centre (ASCC) in 2004 and continues to participate in fundamental research on haemopoietic stem cells and the haemopoietic stem cell niche in collaboration with Associate Professor Susie Nilsson. In July 2009 Associate Professor Haylock joined CSIRO Molecular and Health Technologies, but with his team has remain based in the ASCC laboratories.

Contact details

E-mail	david.haylock@csiro.au
Phone	+61 3 9271 1104

Selected publications

1. To LB, Haylock DN, Kimber RJ and Juttner CA (1984) High Levels of Circulating Haemopoietic Stem Cells in Very Early Remission from Acute Non-Lymphoblastic Leukaemia and their Collection and Cryopreservation. British Journal of Haematology 58: 399-410 (IF 4.49: Citations:190)
2. To LB, Sheppard KM, Haylock DN, Dyson PG, Charles P, Thorp DL, Dale BM, Dart GW, Roberts MM, Sage RE and Juttner CA (1990) Single High Doses of Cyclophosphamide Enable the Collection of High Numbers of Haemopoietic Stem Cells from the Peripheral Blood. Experimental Hematology 18: 442-447 (IF 3.147: Citations:266)
3. To LB, Roberts MM, Haylock DN, Dyson PG, Branford AL, Thorp D, Ho JQK, Dart GWD, Horvath N, Davy MLJ, Olweny CLM, Abdi E and Juttner, CA (1992) Comparison of Haematology Recovery Times and Supportive Care Requirements of Autologous Recovery Phase Peripheral Blood Stem Cell Transplants, Autologous Bone Marrow Transplants and Allogeneic Bone Marrow Transplants. Bone Marrow Transplantation 9:277-84 (IF 3.00:Citations:426)
4. Haylock DN, To, LB, Dowse, TL Juttner, CA and Simmons, PJ (1992) Ex-vivo Expansion and Maturation of Peripheral Blood CD34+ Cells into The Myeloid Lineage. Blood 80:1405-1412 (IF 10.896: Citations:331)
5. Lévesque J-P, Haylock DN and Simmons PJ (1996) Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34+ hemopoietic progenitors. Blood 88:1168-1176 (IF 10.896: Citations:128)
6. Haylock DN, Horsfall MJ, Dowse TL, Ramshaw H, Nuitta S, Protopsaltis S, Peng L, Burrell C, Rappold I, Buhring H-J and Simmons PJ (1997) Increased recruitment of haemopoietic progenitor cells underlies the ex vivo expansion potential of FLT3 ligand. Blood 90:2260-2272 (IF 10.896: Citations:78)
7. and differentiation in vitro. Blood 101:856-862 (IF 10.896: Citations:38)
8. Prince HM, Simmons PJ, Whitty G, Wall DP, Barber L, Toner GC, Seymour JF, Richardson G, Mrongovius R and Haylock DN (2004) Improved hemopoietic recovery following transplantation with ex vivo expanded mobilized blood cells. Br. J. Haematol. 126:536-45 (IF 4.49: Citations:14)
9. Nilsson SK, Johnston HM, Whitty GA, Williams B, Denhardt DT, Bertoncello I, Simmons PJ and Haylock DN (2005) Osteopontin, a Key Component of the Hemopoietic Stem Cell Niche and Negative Regulator of Primitive Hemopoietic Progenitor Cells. Blood 2005 Aug 15;106(4):1232-9 (IF 10.896: Citations:78)
10. DN Haylock, B Williams, HM Johnston, MCP Liu, KE Rutherford, GA Whitty, PJ Simmons, I Bertoncello, SK Nilsson. (2007) HSC with higher hemopoietic potential reside at the bone marrow endosteum. Stem Cells 25:1062-9 (IF 7.531: Citations:12)