Susceptibility To Venous Leg Ulceration: Investigation Of The First Genetic Risk Factor
Funder
National Health and Medical Research Council
Funding Amount
$291,000.00
Summary
This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previ ....This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previous deep vein thrombosis. However, not all patients with a deep vein thrombosis or other forms of venous disease will go on to develop a venous ulcer. Our preliminary results show that patients with a venous ulcer have a greater frequency of this gene than healthy controls without venous ulcers, and suggest that patients with the candidate gene have a greater risk of developing venous ulceration. In this study we aim to determine whether the gene itself contributes to ulcer susceptibility or whether it is just a marker of that susceptibility. We can do this by assessing related genes and the levels of the protein produced by this gene. In this study we also aim to assess whether patients with a proven deep vein thrombosis are more likely to develop venous ulceration if they have the candidate gene. These studies have the potential to lead to the development of a diagnostic screening test for use in patients with venous disease, to assess the likelihood of developing leg ulceration. This will enable more active treatment to prevent leg ulceration. If this gene contributes to ulcer susceptibility new specific treatments may be developed for ulcer management and prevention.Read moreRead less
GENERATION OF VASCULARISED, BIOENGINEERED SOFT TISSUES
Funder
National Health and Medical Research Council
Funding Amount
$445,045.00
Summary
One of the most exciting areas in reconstructive surgery today is the tissue engineering of body parts, the process by which blood vessels are implanted into skin, muscle, bone, cartilage or even synthetic materials, to build composite living structures. Once a circulation becomes established, the engineered part can be transferred by joining the implanted blood vessels to corresponding ones at the recipient site. We have discovered that new tissue will grow out of a surgically created blood ves ....One of the most exciting areas in reconstructive surgery today is the tissue engineering of body parts, the process by which blood vessels are implanted into skin, muscle, bone, cartilage or even synthetic materials, to build composite living structures. Once a circulation becomes established, the engineered part can be transferred by joining the implanted blood vessels to corresponding ones at the recipient site. We have discovered that new tissue will grow out of a surgically created blood vessel loop placed in a cylindrical plastic chamber filled with a scaffold made of naturally occurring structural molecules. In Part 1 of this project, it is planned to optimise the rate of new vascularised tissue growth through the addition to the growth chamber of various biodegradable scaffolds. In Part 2, we aim to produce fat by 3 possible methods using: (a) cells from the rat scrotum, (b) skeletal muscle separated from its blood supply for 24 hours, or (c) bone marrow-derived stem cells, as well as bone from stem cells of the same source. In Part 3, vascularised bone, fat and connective tissue, as produced in Part 2, will be microsurgically transferred to another site in the body to study the short-term (4 weeks) and long-term (12 weeks) survival and changes (if any) in these tissues. These unique methods are currently being patented. This technology introduces the possibility of producing tailor-made tissues of specific composition to suit the repair of a particular tissue type, for example, (1) myocutaneous flaps to replace tissue loss following traumatic injury, (2) bone for nose, digit or joint repair, and (3) fat to provide a bulky flap as required in contour defects of the face and neck. The development of new growth chambers of appropriate body shapes (eg. ears, noses, etc) has significant commercial implications.Read moreRead less
Engineering Tissues And Organs In Vivo From Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$549,480.00
Summary
Tissue engineering is an exciting new area of medical research. We have developed a unique animal model of tissue engineering where new tissue spontaneously sprouts from the surface of a vascular loop enclosed inside a plastic chamber. The tissue thus created has its own blood supply. By adding cultured cells or altering the environment of the chamber we have been able to grow new specific tissues such as fat and muscle. This technology potentially allows the generation of spare body parts to re ....Tissue engineering is an exciting new area of medical research. We have developed a unique animal model of tissue engineering where new tissue spontaneously sprouts from the surface of a vascular loop enclosed inside a plastic chamber. The tissue thus created has its own blood supply. By adding cultured cells or altering the environment of the chamber we have been able to grow new specific tissues such as fat and muscle. This technology potentially allows the generation of spare body parts to replace lost or worn out organs and tissues. We have recently reproduced this model in the mouse to be able to screen a range of mouse and human stem cells. These cells have the ability to change (i.e. differentiate) into many different types of cell depending on how they are stimulated. In Part 1 of this project we will determine in the mouse chamber the growth characteristics and survival rates of these stem cells. A chamber encapsulating a flowing blood vessel will be implanted subcutaneously in each groin. In one chamber we will inject fluorescently labelled stem cells in a growth medium and in the other growth medium alone. Tissue will be analysed at 1, 2 and 4 weeks. In Part 2 we will inject a variety of Rosa26 labelled mouse stem cells obtained from several different tissues. Through the aid of naturally occurring growth and differentiation factors they will differentiate into one of several different tissues including fat, cartilage, bone, neural tissue, blood vessels, liver, etc, which will be identified by histology and cell culture. In one experiment we will genetically alter cells injected into the chamber so that they produce only skeletal muscle. In Part 3 we will grow new human tissues by injecting human stem cells into the same tissue engineering chambers in mice which will tolerate cells from other mammals (these are known as SCID mice). Success in novel method would be the precursor for the production of new human tissues to repair specific defects.Read moreRead less
Evaluation A Novel Vitronectin:growth Factor Complex For Treatment Of Chronic Venous Leg Ulcers
Funder
National Health and Medical Research Council
Funding Amount
$854,975.00
Summary
Chronic leg ulcers in the elderly are an important problem, diminshing quality of life and costing at least A$1 billion per year. New treatments are urgently required. This study will test a new topical growth factor therapy designed to have greatly improved activity in wounds.The project is a collaboration between scientists and doctors at the Queensland Univeristy of Technology and the University of Western Australia. Many wound types may ultimately benefit from this treatment.