The role of hyaluronic acid in the biology of haemopoietic stem cells

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/209090

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 (CAM). This project is based upon the unique observation made in the applicants laboratory demonstrating that both murine HSC and candidate human HSC synthesize the carbohydrate CAM hyaluronic acid (HA). Moreover we have now accumulated data suggesting a key role for HA in determining the spatial distribution 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 HSCs 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 lodgment of a transplant of HSC is not a random process, but results in cells of donor origin being located at the bone-marrow interface. The presence of HA on HSC was critical for this pattern of lodgment. In addition, we have also accumulated evidence suggesting that HA is important in the maintenance of HSC in their primitive state. This proposal aims to confirm the critical role of HA in HSC biology.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $392,090.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical biotechnology diagnostics (incl. biosensors)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

bone marrow transplantation | cell lodgement | cell regulation | haemopoiesis | hyaluronic acid | stem cell biology | stem cells

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