The role of hyaluronic acid in hemopoietic stem cell biology

The adult mammalian hemopoietic system maintains an extraordinarily large, yet well regulated supply of mature blood cells within the circulation throughout life. The system is capable of rapid recovery and compensation following injury, environmental stress or as a result of genetic disease such as the hemoglobinopathies.. Despite the vast amount of research conducted there is still an incomplete understanding of hemopoietic regulation. Nevertheless, it is evident from transplantation studies that ongoing blood cell production is absolutely dependent upon hemopoietic stem cells (HSCs). These rare and potent cells have the capacity for extensive proliferation and the ability to differentiate into all blood cell types. An understanding of HSC regulation is fundamental to understanding hemopoiesis. There is now considerable evidence to demonstrate that in vivo, HSCs are located within defined anatomical sites or niches within the bone marrow. Regulation of HSC fate is mediated by both cell-autonomous mechanisms and extrinsic cues resulting from interactions between cells and extracellular components within the niche. This review focuses on the role of hyaluronic acid, a component of the HSC niche and moreover a HSC-associated glycosaminoglycan, in hemopoiesis and specifically HSC regulation. It is now evident that hyaluronic acid not only provides a physical scaffold or support within the marrow to facilitate localization and retention of HSCs to the stem cell niche but moreover, through ligation with its counter-receptors is able to directly affect the cellular functions of HSCs.