About the Clem Jones Centre for Regenerative Medicine
The Clem Jones Centre for Regenerative Medicine was established to investigate the therapeutic use of stem cells in tissue repair and disease. An important goal of the Centre is to combine research excellence in stem cell science with clinical translation and to enhance, induce or transplant stem cells for patient benefit.
The Centre supports studies in the broader field of regenerative medicine and stem cell biology, combining stem cell science, biomaterials, tissue engineering, tissue regeneration, intelligent drug delivery and advanced surgery.
Current research projects include stem cell therapy for age-related macular degeneration, retinal degeneration, regeneration of spleen from stem cells and enhancing hematopoiesis during ageing and disease.
Research activities in the Centre
The Centre supports several projects on Age-Related Macular Degeneration (AMD), a leading cause of blindness in the aging population. Late-stage AMD is characterised by the dysfunction and death of retinal pigmented epithelial (RPE) cells in the macula, and this is coupled with the breakdown of the underlying Bruch’s membrane. The RPE is a continuous sheet of brown nurse cells that maintains the function and health of the photoreceptors. The combined loss of the Bruch’s membrane and RPE cells leads to photoreceptor dysfunction and death, which in turn causes visual impairment and blindness.
Stem cell therapy is the most promising approach to treating AMD. The central idea is to make replacement RPE cells from stem cells and to implant these cells into the diseased region of the retina to restore photoreceptor function. The combined expertise of members of the whole Centre is focused on the development and testing of retinal implants for the treatment of AMD as a potential treatment for blindness. Retinal implant constructs are comprised of sheets of stem cell-derived RPE cells supported by a prosthetic membrane, where the RPE cells grow and mature to form a uniform monolayer of pigmented cells which function like cells in the healthy eye.
The Centre has been instrumental in the development and testing of porous, synthetic Bruch’s membranes and the retinal construct. He has developed an electrospun membrane which is biodegradable and porous, suitable for supporting RPE cells for implantation into the back of the eye. The thickness and fibre diameter of this synthetic membrane mirrors the physical properties of the native membrane, offering a viable matrix for RPE cells to attach and proliferate.
In collaboration with surgical researchers at the University of Melbourne, the team has perfected procedures for implantation of retinal constructs into the rat eye. Pilot studies are promising, and provide a basis for further improvement and experimentation on constructs for cell delivery.
Retinal cells from stem cells
The production of clinical-grade RPE cells and photoreceptors from stem cells is a central area of research for the AMD project. Jason Limnios brings to Bond a wealth of expertise in the differentiation of human embryonic stem cells and the generation of induced pluripotent stem cells. He has established cell technologies for the AMD project, and developed novel methods for producing clinical-grade retinal cells from human embryonic stem cells. These approaches result in rapid and efficient generation of retinal cells suitable for human clinical trials.
A section of retina fluorescently labelled to show bipolar cells (red) and ganglion cells (green). These and other neuronal cells can be damaged or killed in retinal diseases like diabetic retinopathy and glaucoma.
Diseases of the retina include the common blinding conditions of age-related macular degeneration (AMD), diabetic retinopathy and glaucoma: diseases for which there are currently no cures. Using advanced experimental techniques, including specialist imaging and electrophysiology, we aim to unravel the complex steps that lead to the death of the critical retinal nerve cells in order to develop and target effective protective therapies.
A/Prof Nigel Barnett is currently investigating a number of promising 'neuroprotective' strategies including enhanced antioxidant compounds and targeted drug delivery platforms. "Ultimately, we aim to slow down or even stop the degeneration of vital nerve cells and reduce the loss of vision currently associated with retinal disease."
The spleen has unusual regenerative capacity, and can regrow if fragments are transplanted onto other organs in the body. As a secondary lymphoid organ, the spleen is essential for maintaining blood-borne immunity, especially against organisms such as encapsulated bacteria. It also supports extramedullary hematopoiesis and acts as a backup organ upon disease or damage to bone marrow.
The opportunity to target spleen for therapeutic benefit depends on identification of the structural stem cells necessary for it's development and regeneration. Jonathan Tan leads a research team that has recently identified a stromal organiser cell essential for spleen development. This cell type can co-ordinate the regeneration of spleen tissue and the formation of the immune cell compartments.
The development of blood, including all cells of the immune system, is one of the most well studied areas of stem cell biology. Blood cell formation, or hematopoiesis, occurs primarily in bone marrow, giving rise to hematopoietic stem cells. Transplantation of hematopoietic stem cells is currently the only FDA approved stem cell therapy. Techniques developed in the study of hematopoiesis are now being applied to the study of cell development from many different tissue-specific stem cells. In particular, we are investigating extramedullary hematopoiesis which develops in spleen in response to infection and physiological stressors like pregnancy, blood loss and bone marrow failure.
The spleen is an important hematopoietic organ since it supports the development of immunity to blood-borne pathogens and cancer cells, and plays an important role in the control of sepsis. While spleen offers potential as a backup hematopoietic organ, it also has inbuilt capacity to support steady state hematopoiesis. The group is therefore studying the characteristics of hematopoietic stem cells in spleen and the stromal cells which support their development.
Stem cell microenvironments
Helen O’Neill advances cell development at the single cell level applying this technology to analysis of both hematopoietic and mesenchymal stem cells. The contribution of mesenchymal stromal cells to the formation of niches or microenvironments supporting hematopoiesis is being studied in tissue culture. This work is supported by research to produce ectopic niches for hematopoiesis in mice through transplantation of mesenchymal cells under the kidney capsule. These studies also investigate novel molecules as regulators of hematopoiesis.
Featured media: Video summary of Hey et al. "Antigen presenting capacity of murine splenic myeloid cells” BMC Immunology (2017). doi:10.1186/s12865-016-0186-4
Stem cell therapy for blindness:
- Professor Erica Fletcher, University of Melbourne
- Professor Yasser Ahmed, South Valley University, Luxor, Egypt
- Dr Bob Bourke, Eye Specialist Institute, Gold Coast
- Dr Una Greferath, University of Melbourne
- Dr Kinnari Shelat, University of Queensland
- Professor Damian Harkin, Queensland University Technology
- Professor Steven Bottle, Queensland University of Technology
- Professor Chen Chen, University of Queensland
- Professor Traian Chirila, Queensland Eye Institute
- Dr Harendra Parekh, University of Queensland
Lymphoid tissue regeneration:
- Professor Takeshi Watanabe, Kyoto University, Japan
- A/Prof Michael Doran, Queensland University of Technology
- A/Prof Joseph Powell, Garvan Institute of Medical Research
- Professor Terry O’Neill, Bond University, Gold Coast
- Dr Vinson Tran, University of Western Australia, Perth
- Dr Dipti Talaulikar, Canberra Hospital
- Dr Sawang Petvises, Thammassat University, Bangkok
- Dr Pravin Periasamy, National University of Singapore
- Dr Ying-ying Hey, National University of Singapore
Donation from the Estate of Cora Cutmore to Bond University - Multiyear support - Stem Cell Research
Donation from the Clem Jones Foundation to Bond University - Multiyear support - Age-Related Macular Degeneration
Philanthropic Donations: $170,000 (2016-2017) - Stem cell research
NHMRC - NSFC Joint Call for Research grant to A/Prof Barnett and collaborators from University of Queensland, Queensland Eye Institute and Capital Medical University, China - $598,305 (2016 - 2020) - Biomarkers for the treatment and prognosis of sight-threatening diabetic retinopathy
NHMRC New Investigator Project grant to Jonathan Tan - $401,398 (2015-2018) - Understanding the mechanisms that regulate spleen organogenesis
ARC Discovery grant to Helen O’Neill - $390,000 (2013-2017) - Microenvironments which support extramedullary hematopoiesis
NHMRC Ideas grant to Nigel Barnett, Helen O'Neill and Steven Bottle (QUT) - $683,000 (2020-2023) - Retinal stem cell therapy in the immunoprivileged eye.