Using Direct Reprogramming To Generate And Rejuvenate Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,026,313.00
Summary
One of the greatest promises of regenerative medicine lies in our ability to reprogram any cell type of the body into any other cell type. Transdifferentiation is the conversion of one adult cell type to another and it is believed to be the next frontier in regenerative medicine therapies since it can be used in vivo for the direct conversion of one cell type into another. The outcomes of this grant will push the limits of these technologies to generate new regenerative medicine strategies.
Generating Haematopoietic Stem Cells From Human Pluripotent Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$872,215.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells. Using a new approach that we have developed, our laboratories will make blood stem cells from human pluripotent stem cells that will treat patients needing a transplant.
Characterization Of HOXA-expressing Human Haematopoietic Cells Generated From Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$622,464.00
Summary
Blood stem cell transplants are used for treating a range of human blood disorders such as leukaemias. However, for many patients, suitable donors cannot be found. We are searching for ways in which embryonic stem cells can be turned into blood stem cells in the laboratory to provide a new source of these cells that could then be used to treat patients.
Twist-1 Inhibits MSC Osteoblast Differentiation During Osteoporosis Via Direct Regulation Of The Wnt Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$482,704.00
Summary
There is a predicted dramatic increase in the number of orthopaedic related problems that require surgical intervention and rehabilitation therapy in the coming decade associated with higher incidences of bone diseases as a consequence of an aging population. This proposal seeks to determine whether the transcription factor, Twist-1 plays a central role in regulating the growth and differentiation of skeletal progenitors during bone loss following the onset of osteoporosis.
Transcriptional Regulation Of Definitive Hematopoietic Development In Humans
Funder
National Health and Medical Research Council
Funding Amount
$800,036.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells, such as human pluripotent stem cells. During development, blood cells are formed from the blood vessel wall, or endothelium. In this project, we will study the regulation of this process in order to more efficiently make human blood cells in the laboratory.
The intestinal lining is continuously renewed by specialised cells called intestinal stem cells. Stem cells throughout the body are regulated by nearby connective tissues. But, the identity of these supportive cells in the gut are unknown. We test whether a discrete population of connective tissue cells in the gut support intestinal stem cells. This project will identify new cellular therapies and targets to promote intestinal repair and manage intestinal cancer.
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.
Does Nuclear Reprogramming Of Granulocytes Induce Reversal Of The Hematopoiesis Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$461,805.00
Summary
Generation of induced pluripotent stem cells has enormous therapeutic potential. However, it is unclear whether de-differentiation to pluripotency proceeds via a reversion of the same developmental pathway that gave rise to the cell type being reprogrammed. To answer this we will dissect the reprogramming process within the well defined hematopoietic system and assess the generation of hematopoietic precursor-like cells during reprogramming.
Cardiovascular diseases and heart failure rates are increasing worldwide. This is largely a result of the heart’s limited capacity for self-repair. Stem cells now provide an exciting potential novel therapy. We have recently demonstrated the feasibility of this therapy in a preclinical model of heart attack. Nevertheless, further work is required before human clinical trials can take place. This project will dismantle barriers preventing progression to these clinical trials.
Reprogramming is the conversion of any cell into induced pluripotent stem cells (iPSC). iPSC carry immense clinical potential as they are pluripotent and can hence form any cell of the human body, however, they can also form tumours. We have identified a cell type during reprogramming which is pluripotent but cannot form tumours. It is the aim of this project to characterize these cells as well as to confirm their existence during human reprogramming.