Module 1: Assessment of ‘Smart’ Surfaces for Culture of Haemopoietic Stem Cells and Megakaryocytic Cells

Haemopoietic stem cells in culture

Module description

The objective for this component of the bioreactor program is to evaluate a range of novel surfaces and materials for their ability to support the survival, proliferation and differentiation of human haemopoietic stem cells.

There are two discrete, but linked components of research to be undertaken in this module. In brief, the focus for this work is the development of polymeric based surfaces that enable the tethering and presentation of biological ligands for stimulating proliferation and differentiation of haemopoietic stem cells (HSC) and or their differentiated progeny. The second component involves the development of a novel method for megakaryocytic cell propagation and differentiation. These two components are linked through the need to develop novel tissue culture surfaces and the use of thrombopoietin mimetics.

The two research activities share a common hypothesis that characteristics of tissue culture surfaces and presentation of biological ligands (haemopoietic growth factors or cytokines) in an immobilised form enhances proliferation and differentiation of HESC and megakaryocytic cells.

Aims

1. Develop and screen thrombopoietin (TPO) mimetics.
2. Develop and validate surfaces that facilitate tethering of biological ligands. 
3. Develop a novel method for propagation of megakaryocytic cells and platelets based on electrospun scaffolds.

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

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)