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
There are a number of important medical conditions that are characterised by a loss of bone. These include osteoporosis, cancer-induced bone loss, and the bone loss that causes loosening of orthopaedic prostheses. Bone loss is understood to be due to an excess of bone resorption by osteoclasts in relation to bone formation. Understanding of the regulation of osteoclast formation and activity has increased greatly in the last few years, but important questions remain. In particular, more informat ....There are a number of important medical conditions that are characterised by a loss of bone. These include osteoporosis, cancer-induced bone loss, and the bone loss that causes loosening of orthopaedic prostheses. Bone loss is understood to be due to an excess of bone resorption by osteoclasts in relation to bone formation. Understanding of the regulation of osteoclast formation and activity has increased greatly in the last few years, but important questions remain. In particular, more information is needed about the process of human osteoclast formation. We have devised a novel cell culture model of human osteoclast formation, in which osteoclast precursor cells mature into osteoclasts under the influence of human osteoblast cells. The importance of this model is that it allows us, for the first time, to investigate the role, and the potential relevance in human disease, of agents that positively and negatively affect osteoclasts. We intend also to use this model to study the way in which cancer cells in bone cause bone loss, as well as the involvement of cells of the immune system in osteoclast formation, in normal bone and in inflammatory conditions.Read moreRead less