Assessment Of The Properties Of Mesenchymal Stem Cells And Their Role In Skeletal Tissue Repair And Disease
Funder
National Health and Medical Research Council
Funding Amount
$751,854.00
Summary
There is currently a steady increase in surgical intervention and rehabilitation therapy for bone related fractures due to trauma or osteoporosis as a consequence of an aging population. Bone regeneration involves the coordinated participation of skeletal precursor cells, blood vessels and immune cells recruited from the surrounding tissues. This proposal examines the mechanisms mediating the maintenance and recruitment of skeletal precursor cells to sites of bone damage.
Regulation Of Normal And Malignant Haematopoiesis By The Bone Marrow Environment
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
This project will identify factors within the bone marrow that regulate blood and immune cell formation. These include oxygenation and novel proteins identified in the applicant’s laboratory. How these factors from the bone marrow influence the behaviour of normal blood forming cells (called haematopoietic stem cells), and the progression of leukaemia and the response of leukaemia to chemotherapy treatments will be investigated. New drugs that interfere with these new factors will be tested for ....This project will identify factors within the bone marrow that regulate blood and immune cell formation. These include oxygenation and novel proteins identified in the applicant’s laboratory. How these factors from the bone marrow influence the behaviour of normal blood forming cells (called haematopoietic stem cells), and the progression of leukaemia and the response of leukaemia to chemotherapy treatments will be investigated. New drugs that interfere with these new factors will be tested for their potential to treat leukaemia.Read moreRead less
The Molecular Mechanisms Controlling Maintenance Of Osteogenic Precursor Cells And Skeletal Tissue Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bon ....Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bone resorption by osteoclasts, but may also occur through a decline in the number of bone forming cells called osteoblasts or their progenitors. Fracture non-union, prosthetic loosening and the replacement of large defects in bone are common and difficult problems. The use of autologous bone cells generated from isolated BMSSCs in combination with bio-compatible implant materials would provide a novel solution for the treatment of these problems, avoiding the use of autografts and allografts of bone with all their associated difficulties. However, large numbers of ex vivo expanded BMSSCs are currently required to heal even small bone defects in animal models. This is compounded by the decline in proliferation rates and bone forming capacity of BMSSCs during prolonged expansion in culture. An improved understanding of the genes that regulate the proliferation and differentiation of BMSSCs in vitro is therefore an essential prerequisite for the effective management of bone fracture and bone loss. We propose to genetically manipulate the expression of genes in BMSSCs, that are known to regulate cellular growth and development inorder to maintain the growth of stem cell populations in vitro and to extend their capacity to form bone when transplanted in vivo.Read moreRead less
Hematopoietic Effects Of Activating The Hedgehog Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$410,551.00
Summary
The hedgehog proteins are important for normal human development. They are expressed on cells of the brain and developing limbs and provide important signals to neighbouring cells so that development of the brain and limbs can occur normally. Mutations in genes within the hedgehog signalling pathway lead to congenital abnormalities such as failure of the brain to fold properly and shortened limbs or extra digits. Hedgehog proteins also stimulate the growth of adult stem cells that are responsibl ....The hedgehog proteins are important for normal human development. They are expressed on cells of the brain and developing limbs and provide important signals to neighbouring cells so that development of the brain and limbs can occur normally. Mutations in genes within the hedgehog signalling pathway lead to congenital abnormalities such as failure of the brain to fold properly and shortened limbs or extra digits. Hedgehog proteins also stimulate the growth of adult stem cells that are responsible for the maintenance of many adult tissues such as the skin, bone and hair. Excessive hedgehog signalling however can lead to cancers, particularly of the brain and skin. The ability of hedgehog proteins to stimulate the growth of stem cells raises their use for expansion of stem cells. This would be particularly useful for umbilical cord blood stem cells, which could be used to treat patients with leukemia if there were sufficient numbers. This project will examine the potential use of hedgehog proteins for stimulating blood stem cells.Read moreRead less
Do Bone Marrow Macrophages Regulate Leukaemia Stem Cells And Their Response To Treatment?
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
This project will investigate the role of population of immune cells called macrophages in promoting resistance of leukaemia cells to chemotherapy treatments. As a high proportion of adult patients with acute leukaemia cannot be cured with current treatments, this project could lead to more efficacious therapies targeting macrophages to sensitise leukaemia cells to chemotherapy treatments.
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.
Recipient Bone Marrow Macrophages Contribute To Haematopoietic Stem Cell Transplantation Success
Funder
National Health and Medical Research Council
Funding Amount
$608,906.00
Summary
We propose an innovative approach to reduce risk and increase success of blood stem cell transplantation. We will determine whether a specialized cell within the transplant patient is required for donor stem cells to successfully take up residence and recreate the blood and immune system. We will test whether fortifying these specialized cells will improve transplantation outcomes, consequently increasing the number of transplants that can proceed and reducing potentially fatal complications.