Characterisation Of Human Embryonic Stem Cell Differentiation To Haematopoietic Progenitors And Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$638,856.00
Summary
Blood stem cells, which are found in the bone marrow, are currently used for treating human blood disorders including leukemia and lymphoma. However, for the majority of bone marrow transplant candidates, suitable donors cannot be found. Using embryonic stem cells, this project aims to define the conditions required to generate blood stem cells in the laboratory. The aim of the work is to provide a new source of blood stem cells that could be used in place of donor derived bone marrow.
Bone Marrow Endothelial Stem Cells Have The Capacity To Form Both The Endothelial And Haemopoietic Hierarchies
Funder
National Health and Medical Research Council
Funding Amount
$1,452,856.00
Summary
Blood cell formation is hierarchically organised; with hemopoietic stem cells (HSC) responsible for producing mature circulating blood cells. HSC reside in marrow near blood vessel cells. Although these play a key role in HSC regulation their origin in adults is poorly understood. We have demonstrated the existence of adult marrow vessel stem cells at the apex of a parallel hierarchy. Our objective is to characterise these in mice and humans and determine their role in blood malignancies.
Investigating The Formation And Utility Of The Prenatal Platelet Forming System
Funder
National Health and Medical Research Council
Funding Amount
$793,442.00
Summary
A major challenge to regenerative medicine is discovering how to produce useful cell types in the laboratory. Particularly urgent is the need to generate large numbers of platelets, the building blocks of the clotting system, for clinical use. Current laboratory methods are woefully inefficient, thus cannot meet demand. This project aims to discover how platelets are made in nature. With this information we will be able to devise better platelet production strategies in the laboratory.
Production Of Large Scale Erythroid Progenitor Cultures From Human Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$396,718.00
Summary
Transfusion of fresh red blood cell units of the correct blood type into patients can be life saving. However, access to units of the correct blood type is often limited due to limited supply of donor blood and its short shelf life creating the need for a constant donor blood supply. We propose to develop a system that allows us to generate unlimited numbers of human red blood cells in a culture dish which we will derive from differentiating human embryonic stem cell lines.
Understanding The Ancestry Of De Novo Blood Formation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$484,666.00
Summary
Current laboratory methods rely on a hit-or-miss approach for the production of such cells, making the prospect of producing patient-specific cells an inefficient/financially prohibitive process. This project aims to generate new knowledge into when and how fate of early blood cells in selected in nature. With this information we will be able to devise effective blood progenitor cell production strategies in the laboratory.
Role Of Beta-catenin And Its Regulator FAM In Haemopoietic Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$506,500.00
Summary
Haemopoietic stem cells (HSC) are currently the best characterised adult stem cell (SC) population and currently the only SC population used in cellular therapy. Adult HSC reside in the bone marrow and it is generally accepted that these rare cells cycle slowly and maintain themselves by a process involving self renewal. The cellular physiology that underlies HSC self renewal is still to be defined and no single factor has been described which is able to induce substantial proliferation and expa ....Haemopoietic stem cells (HSC) are currently the best characterised adult stem cell (SC) population and currently the only SC population used in cellular therapy. Adult HSC reside in the bone marrow and it is generally accepted that these rare cells cycle slowly and maintain themselves by a process involving self renewal. The cellular physiology that underlies HSC self renewal is still to be defined and no single factor has been described which is able to induce substantial proliferation and expansion of HSC in a defined system while maintaining critical stem cell properties. Like other SC, a critical characteristic of the rare HSC population of cells is their ability to maintain their unique stem cell properties in vivo (the process of self-renewal) while generating more committed cells which will form large numbers of differentiated and specialized mature blood cells. Recent evidence that HSC can repair other organs under some circumstances raises the possibility that this adult SC population could provide an alternative to embryonic stem cells for many stem cell therapies. If this is the case the therapeutic application of HSC becomes significantly broader. Critical to development of such applications will be an understanding of HSC self renewal and development and new approaches to expand this limited cell population. Major progress in this area will require the definition of both the intrinsic and extrinsic mechanisms that control HSC maintenance and self-renewal. Any findings in this area will have major clinical significance and be of enormous benefit to the community. Here we focus on the role of a known intrinsic regulator of SC behaviour (beta-catenin) with the aim of establishing its role in the maintenance of HSC and its regulation by a novel cofactor (FAM). We will determine if the level of beta-catenin is critical in the maintenance and-or differentiation of haemopoietic stem cells and what role FAM plays in this regulation.Read moreRead less
Endocytosis And Asymmetric Cell Division In Leukemia.
Funder
National Health and Medical Research Council
Funding Amount
$548,258.00
Summary
Self-renewal allows normal haematopoeitic stem cells to constantly replenish the blood system. Conversely, leukemia stem cells use self-renewal to propagate the disease, and utilise the quiescence phase to evade treatment eradication. We identified that the endocytic gene, Ap2a2 enhances haematopoeitic stem cell self-renewal. Through Ap2a2, we are now investigating the role of endocytosis and self-renewal in leukemia and ex vivo expansion of human haematopoietic stem cells.