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.
Haematopoietic Stem Cell Glycome Regulates Outcome Of Niche Interactions
Funder
National Health and Medical Research Council
Funding Amount
$913,729.00
Summary
Hematopoietic stem cells (HSC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a factor in the BM which when blocked, puts normal HSC to sleep helping them survive chemotherapy. This means cancer patients should suffer less side-effects from their therapy. This factor also helps leukaemia stem cells (LSC) resist chemotherapy. Inhibitors may a) reduce patient mortality caused by chemotherapy and b) sensitise LSC to chemotherapy enabling long-term cure.
(Re)wiring A Stem Cell: Deciphering The Molecular Mechanism Underpinning Lineage Propensity
Funder
National Health and Medical Research Council
Funding Amount
$855,780.00
Summary
This project explores the response of the stem cells to cues that direct how they turn into specific type of cells that is suitable for clinical use. Specifically, a set of driver genes whose activity can foretell the outcome of cell differentiation will be identified. By modulating the maintenance conditions, iPSCs lines may be tailored for specific applications in stem cell therapy and disease modelling for the assessment of treatment efficacy.
Osteochondroreticular Stem Cell Therapy For Osteoarthritis: The Right Cells For The Job.
Funder
National Health and Medical Research Council
Funding Amount
$561,956.00
Summary
"Wear and tear" arthritis of the knee, hip and back joints is known as osteoarthritis. This causes significant health burden and costs in our community, particularly in older Australians. Osteoarthritis begins with the loss of joint cartilage. We believe that a new type of stem cells (OCR stem cells) offer the greatest promise to generate and thus therapeutically replace joint cartilage. Our studies test this hypothesis and develop preclinical translation of our discoveries in mice into humans.
A Simple Method To Improve Stem Cell Transplant Therapy
Funder
National Health and Medical Research Council
Funding Amount
$831,652.00
Summary
Despite the success of hematopoietic stem cell transplantation and years of promise, almost all other stem cell therapies are considered experimental and remain in preclinical or early-phase clinical testing. This study aims to improve the efficiency of stem cell transplantation by manipulating cellular metabolism prior to transplantation, if effective these results may offer hope to patients suffering from a broad range of disorders.
Neurons within the wall of the bowel play an essential role in gut motility. A number of motility disorders are caused by diseased enteric neurons, but there are currently no effective treatments for these diseases. We will use animal models of a pediatric motility disorder to examine whether stem cells implanted into the colon can generate neurons and restore normal motility.
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.
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.