Module 7: Haemopoietic Stem Cells and their Niche

Transplanted HSC/HPC (red) next to a megakaryocyte (image courtesy of Jochen Grassinger)

Module Leader Associate Professor Susie Nilsson
Host Organisation CSIRO

Module description

Research within this module is aimed at understanding the role of the haemopoietic microenvironment in haemopoietic stem cell (HSC) biology. Specifically, this involves further identifying and characterising the mechanisms involved in attracting, retaining, regulating and releasing HSC from the bone marrow stem cell niche. This is essential to be able to maximise as well as manipulate HSC potential in both normal and disease states.

In addition, understanding of the HSC niche will allow the cross fertilisation of scientific knowledge, methodologies and reagents to other adult organs to aid in the identification and characterisation of additional specific stem cell niches in tissues such as lung, heart and kidney.

Aims

  1. To determine the molecular profile of HSC/progenitor cells (HPC) within the endosteal niche compared to those in other regions of the bone marrow.
  2. To characterise the interactions between HSCs and megakaryocytes (Mks) within the endosteal stem cell niche.
  3. To characterise changes in the niche following myeloablation.
  4. To optimise the number and evaluate the quality of HSC/HPC mobilised by newly developed HSC mobilisation agents.

Module Leader biography

In July 2009 Associate Professor Susie Nilsson (nee Begg) joined CSIRO Molecular and Health Technologies but along with her team remains based in the ASCC laboratories. Prior to this, Associate Professor Nilsson was the head of the Niche Laboratory at the Australian Stem Cell Centre having moved from the Peter MacCallum Cancer Centre at the end of 2005, where she was head of the Microenvironment Laboratory within the Stem Cell Program.

Associate Professor Nilsson’s underpinning scientific objective has been to characterise the haemopoietic stem cell niche. She developed an in vivo cell tracking model to identify haemopoietic stem cells (HSC) in situ and was one of the first investigators to provide convincing evidence that HSC preferentially seek and reside within the endosteal region of the bone marrow.

Associate Professor Nilsson is the author of 45 publications, including 32 in the past 10 years. During this time she has been invited to submit five peer reviewed papers and five book chapters.

In the past decade, she been awarded six patents, all of which are at various stages from provisional applications to national phase. She is currently a member of the Board of Directors of Experimental Haematology and a member of the International Society for Stem Cell Research.

Contact details

 E-mail  susie.nilsson@csiro.au
 Phone  +61 3 9271 1150

Selected publications

  1. S.K. NILSSON, D.N. Haylock, H.M. Johnston, T. Occhiodoro, T.J. Brown, P.J. Simmons. (2003) Hyaluronan is synthesised by primitive hemopoietic cells, participates in their lodgement at the endosteum following transplantation and is involved in the regulation of their proliferation and differentiation in vitro. Blood 101:856-62.
  2. R.L. Driessen, H.M. Johnston, S.K. NILSSON. (2003) Membrane-Bound Stem cell Factor Is a Key Regulator in the Initial Lodgement of Stem Cells within the Endosteal Marrow Region. Exp Hematol 12: 1284-1291.
  3. S.K. NILSSON, H.M. Johnston, G.A. Whitty, B. Williams, R.J. Webb, D.T. Denhardt, I. Bertoncello, L.J. Bendall, P.J. Simmons, D.N. Haylock (2005) Osteopontin, a Key Component of the Hematopoietic Stem Cell Niche and Negative Regulator of Primitive Hematopoietic Progenitor Cells. Blood 106:1232-1239.
  4. D.N. Haylock, S.K. NILSSON (2005) Stem cell regulation by the haemopoietic stem cell niche. Cell Cycle 4:1353-1355.
  5. D.N. Haylock, S.K. NILSSON (2006) Osteopontin: A bridge between bone and blood. Br. J. Haematol. 134:467-74.
  6. D.N. Haylock, S.K. NILSSON (2006) The role of hyaluronic acid in hemopoietic stem cell biology. Reg. Med. 1:437-445.
  7. D.N. Haylock, B. Williams, H.M. Johnston, M.C.P Liu, K.E. Rutherford, G.A. Whitty, P.J. Simmons, I. Bertoncello, S.K. NILSSON. (2007) HSC with higher hemopoietic potential reside at the bone marrow endosteum. Stem Cells. 25:1062-1069.
  8. S.K. NILSSON, H.M. Prince, D. Wall, D.N. Haylock. (2007) Recent Australian Experience with Haemopoietic Stem and Progenitor Cell Expansion. Cytotherapy. 9:231-235.
  9. D.N. Haylock, S.K. NILSSON (2007) Expansion of umbilical cord blood for clinical transplantation. Current Stem Cell Research & Therapy. 2:324-335.
  10. J. Grassinger, D.N. Haylock, M. Storan, G.O. Haines, B. Williams, G.A. Whitty, A. Vinson, C.L. Be, S. Li, E.S. Sørensen, P.L. Tam, D.T. Denhardt, D. Sheppard, P.F. Choong, S.K. NILSSON (2009) Osteopontin is critical for the attraction, retention, regulation and release of hemopoietic stem and progenitor cells to, in and from their bone marrow niche in a process mediated by α9β1 and α4β1 integrins. Blood. 114:49-59.