The role of hyaluronic acid, CD44 and osteopontin in haemopoietic stem cell biology

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/350446

Funding Status
Closed

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Funded Activity Summary

Marrow and microenvironmental cell (MC) interactions play a central role in bone marrow (BM) cell localisation and regulation. Specifically, the regulation of primitive blood cells (HSC) is affected by their locality and their expression of a wide repertoire of cell adhesion molecules. This project is based upon the unique observations made in the applicants laboratory demonstrating that the three molecules hyaluronic acid (HA), CD44 and osteopontin play key roles in the localisation of HSC within the BM following transplantation and in regulating their development into mature blood cells. Encapsulating the concept of highly specific, local interactions regulating blood cells is the 'niche' hypothesis in which MC form a specific 'niche'. The current inability to identify HSC in situ makes it impossible to analyse either their distribution or molecules that regulate this process. Circumstantial evidence suggests the presence of HSC 'niches' in close association with the bone. Using a novel approach based on BM transplantation to track cells lodging in the BM, we were the first to report that the lodgement of a transplanted HSC is not a random process, but results in cells of donor origin migrating to the bone-marrow interface. The presence of HA and CD44 on the HSC and CD44 and ostepontin in the marrow microenvironment are critical for this pattern of lodgement. In addition, we now have evidence that HA and osteopontin are important in the maintenance of HSC in their primitive state. This proposal aims to confirm the critical roles and interactions of these three molecules in HSC biology.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $472,062.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

CD44 | Hyaluronic acid biology | Ostepontin | bone diseases | bone marrow transplantation | cancer therapy | haemopoietic microenvironment | haemopoietic stem cell homing and engraftment | stem cell therapy

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