Clem Jones Research Centre for Regenerative Medicine

Overview

The Clem Jones Research 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, regeneration of spleen from stem cells and enhancing hematopoiesis during ageing and disease. 

Centre Staff   Research Students & Projects

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.

Biomaterials

Denver Surrao 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.

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 supports extramedullary hematopoiesis and acts as a backup organ upon disease or damage to bone marrow.

This project involves the use of spleen tissue grafting and regeneration models, single cell sorting, transplanting hematopoietic stem cells and trancriptome profiling. The function of spleen in hematopoiesis, and particularly myelopoiesis, is not well understood, and the production of myeloid cells for wound healing and inflammation in other parts of the body is under investigation.

Spleen organogenesis

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 has recently identified an endothelial type progenitor, called the "stromal organiser cell', which is essential for development of this important organ.  This cell can regenerate the vasculature which supports the development of the sinusoidal network which underlies the formation of the immune cell compartments in spleen.

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.

Recent recognitions

Recent publications:

Tan, JKH and Watanabe, T. (2017) Stromal cell subsets directing neonatal spleen regeneration. Scientific Reports 7: 40401. DOI: 10.1038/srep40401

Tan, JKH and Watanabe, T. (2014) Murine spleen tissue regeneration from neonatal spleen capsule requires lymphotoxin priming of stromal cells. Journal of Immunology 193, 1194-1203. DOI: 10.4049/jimmunol.1302115. 

Conference presentations:

Presenter at the EMBL Conference on Hematopoietic stem cells: from the embryo to the aging organism, Heidelberg, Germany, 2016 - Identifying tissue-resident hematopoietic stem cells in extramedullary sites

Invited speaker at the ASMR 55th National Scientific Conference, Gold Coast, 2016 - A Stromal Organiser Cell that Directs Neonatal Spleen Regeneration

International Society for Hematology Travel Grant, Japan, 2015     

Recent publications:

Papathanasiou P, Petvises S, Hey YY, Perkins A, O’Neill HC. (2017) Impact of the c-MybE308G mutation on mouse myelopoiesis and dendritic cell development. PLoS ONE 12(4): e0176345. https://doi.org/10.1371/journal.pone.0176345

Hey YY, Quah B, O’Neill H.C. (2017) Antigen presenting capacity of murine splenic myeloid cells. BMC Immunology 18(1): 4. https://doi.org/10.1186/s12865-016-0186-4

Hey YY, O’Neill HC. (2016) Antigen presenting properties of a myeloid dendritic-like antigen presenting cell in murine spleen. PLoS ONE 11(9): e0162358. https://doi.org/10.1371/journal.pone.0162358

Hey YY, Tan JKH, O’Neill HC. (2016) Redefining myeloid subsets in murine spleen. Frontiers in Immunology, 6: Article 652, pp1-12. DOI: 10.3389/fimmu.2015.00652     

Public lectures: 

Invited speaker for Bond University Women’s Network Symposium, Research Week, 2016 - Under the Microscope: Working in Medical Research

Public Lecture for Research Week at Bond University, 2015 - Stem Cells: Where do they hide?

Invited speaker at DC Downunder Sydney, 2015 - Dendritic cell development in spleen

Recent publications:

Surrao DC, Grerefath U, Chau Y-Q, Skabo S, Huynh M, Shelat KJ, Limnios IJ, Fletcher EL, Liu Q. (2017) Design, development and characterization of synthetic Bruch's membranes Acta Biomaterialia, In press.

Conference invitations:

Invited to speak at the Association for Research in Vision and Ophthalmology conference, Seattle, 2016 - Design, Development & Evaluation of Electrospun Nanofibrous Membranes as Scaffolds for Retinal Pigment Epithelium Cells

Invited Speaker, ASMR 55th National Scientific Conference, Gold Coast, 2016 - Design, Development and Characterization of Synthetic Electrospun Nanofibrous Membranes for Retinal Pigmented Epithelium Cells

Invited speaker at TERMIS-EU: Personalised therapies for regenerative medicine, Switzerland, 2017 - Tissue Engineered Retinal Implants – one step closer to treating dry age-related macular degeneration

People’s Choice Award for Oral Presentations, Bond University HDR Conference, 2016

Research Support

Dr Bob Bourke, Eye Specialist Institute, Gold Coast

Professor Erica Fletcher, University of Melbourne

Dr Una Greferath, University of Melbourne

Professor Yasser Ahmed, South Valley University, Luxor, Egypt

Dr Kinnari Shelat, University of Queensland

Dr Jacob Cook, Eye Specialist Institute, Gold Coast

Professor Damian Harkin, Queensland University Technology

Professor Takeshi Watanabe, Kyoto University, Japan

Dr Vinson Tran, University of Western Australia, Perth

Dr Dipti Talaulikar, Canberra Hospital

Dr Ben Quah, Australian National University

Dr Sawang Petvises, Thammassat University, Bangkok

Dr Pravin Periasamy, National University of Singapore

Dr Ying-ying Hey, National University of Singapore

Professor Terry O’Neill, Bond University, Gold Coast

Dr Kristin Griffiths, Genentech, San Francisco

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 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