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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
In Vivo Tissue Engineering Of Adipose Tissue For Reconstructive Surgery
Funder
National Health and Medical Research Council
Funding Amount
$713,545.00
Summary
We are able to grow vascularised tissue in implanted plastic chambers to a predetermined size and shape in the rat and mouse (NHMRC Project Grant 01-03; #145782; CIA Morrison). The basis of this growth is blood vessel sprouting from the surface of the vessel bundle or loop, followed by synthesis of structural molecules and the migration of surrounding cells into the vascularised network to form a stable tissue. Unlike other in vivo models of tissue engineering, the tissue grows spontaneously and ....We are able to grow vascularised tissue in implanted plastic chambers to a predetermined size and shape in the rat and mouse (NHMRC Project Grant 01-03; #145782; CIA Morrison). The basis of this growth is blood vessel sprouting from the surface of the vessel bundle or loop, followed by synthesis of structural molecules and the migration of surrounding cells into the vascularised network to form a stable tissue. Unlike other in vivo models of tissue engineering, the tissue grows spontaneously and is densely vascularised, enabling continuous growth and surgically transfer to another part of the body, or to another animal. In this renewal application of the above NHMRC grant, we propose to direct these findings towards the development of vascularised fat tissue which would be ideal for reconstructive surgery as a stable, inert tissue filler. Our efforts to grow fat tissue in vivo to date have identified 4 major requirements: a fat precursor cell source; an instructive basement membrane matrix (which may include growth-differentiation factors); space into which the tissue can grow; a stable blood supply. We will focus here on optimising the precursor cell source and instructive matrix to generate vascularised fat tissue around the blood supply we can engender in our tissue engineering chamber. We have found Matrigel, a mouse tumor-derived matrix rich in basement membrane components, to be instructive for growing fat, and will also build on preliminary observations that either muscle or fat tissue can provide the appropriate precursor cells for this process. Finally we propose to adapt and upsize the vascularised fat tissue chamber to the pig, in a step towards human use, and assess its transplantability and longevity. The clinical application of our work is to produce breast reconstruction tissue and lipo filling for contour deformities resulting from trauma, congenital deformity, ageing and cancer surgery, particularly breast reconstruction.Read moreRead less
The Role Of Dysregulated VEGFs In Lymphatic And Non-lymphatic Vascular Malformations
Funder
National Health and Medical Research Council
Funding Amount
$389,486.00
Summary
Vascular malformations are abnormal growths of blood vessels that affect hundreds of children born in Australia every year. They range from small birthmarks to large destructive growths that cause chronic pain, bleeding and major deformity. This is the largest ever study to systematically look for the biological drivers that cause these growths so that drug treatments will ultimately be able to replace surgery as the first line treatment.
Targeting The AGE-RAGE Axis In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$542,859.00
Summary
Based on extensive preliminary data we porpose that the AGE intercation with RAGE plays an important role in diabetes associated atherosclerosis. We will perform studies using a soluble form of the receptor RAGE which will trap AGEs in the blood and tissues and thus prevent diabetes related blood vessel damage. Furthermore, we will investigate if RAGE receptor on inflammatory cells such as macrophages plays a pivotal role in blood vessel injury in diabetes.
Molecular Investigations Of The Neuroprotective Activity Of Estrogen, Phytoestrogens, And Phytosterols
Funder
National Health and Medical Research Council
Funding Amount
$270,872.00
Summary
Estrogen protects women from heart and brain disease but more women will spend over a third of their lives in the postmenopausal state, which is characterized by reduced estrogen levels. Many studies suggest that estrogen-like compounds produced by plants may provide health benefits and alleviate the symptoms of menopause. We investigate the protective effects of such compounds in nerve cells, to address the unmet need for safe and effective prevention and treatment of neurological diseases.
Role Of Circulating Advanced Glycation End Products (AGEs) In Diabetic Nephropathy: Effect Of Benfotiamine Intervention
Funder
National Health and Medical Research Council
Funding Amount
$465,000.00
Summary
Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that all ....Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that allow the comprehensive quantification of individual AGE levels in blood. Our study involves the comparison of AGE blood levels, as a group or as specific AGEs with markers of diabetic kidney disease such as albumin (protein) excretion in the urine and the rate that the kidney filters the blood to form urine (glomerular filtration rate). Benfotiamine is a thiamine (vitamin B1) derivative that has been shown to decrease the formation of AGEs and to prevent kidney disease in diabetic animals. The present clinical study will assess whether benfotiamine has similar effects on AGEs and kidney disease in patients with type 2 diabetes. If successful, this study has the potential to provide a new treatment strategy for diabetic kidney disease in humans.Read moreRead less
Restricting Dietary Advanced Glycation End Product Intake As A Potential Therapeutic Tool In Diabetic Nephropathy.
Funder
National Health and Medical Research Council
Funding Amount
$483,351.00
Summary
Kidney disease is a serious complication of diabetes and may occur as a result of a biochemical process known as advanced glycation. These advanced glycation end products (AGEs) accumulate in the kidney causing disruption of function. Due to modern food processing techniques, the Australian diet has a high AGE content. Over-eating foods which are high in AGEs may worsen diabetic kidney disease. This proposal will test the effects of dietary AGE restriction and overfeeding on kidney function.