Every day when I come to work at the Centre for Eye Research Australia, based in the Royal Victorian Eye and Ear Hospital, I see many patients suffering from different eye diseases. Some of them have low vision; some of them are legally blind. Often I ask myself the same question: can my research with stem cells help these patients?
Blindness is one of the most feared disabilities and many common causes of blindness are currently untreatable. To treat a disease, we have to first study and understand it. However, it is very difficult to obtain eye tissue from living patients so that we can study these diseased cells in the laboratory.
As a stem cell biologist, I believe that pluripotent stem cells will serve as a valuable cellular model for this purpose. Pluripotent stem cells possess two fascinating characteristics:
- they can differentiate and become any cell types in the body, and
- they can be grown indefinitely in the laboratory; providing an unlimited source of cell supply.
Technological advances now allow us to generate pluripotent stem cells from a patient’s cells (such as skin fibroblast cells, obtained by biopsy) by a process called ‘reprogramming’. These stem cells are known as human induced pluripotent stem (iPS) cells. The discovery of the iPS cell technology has revolutionised the field of regenerative medicine and was recognised by the award of the Nobel Prize for Medicine in 2012 to Professor Shinya Yamanaka.
iPS cells have multiple therapeutic potentials including: disease modelling, drug discovery and cell replacement therapy.
Firstly, iPS cells can be used for disease modelling. iPS cells can be generated from patients and differentiated into the cell type that is affected by the disease, which allow the study of diseased cells in the laboratory and understanding the mechanism responsible for the disease. This disease modelling approach using iPS cells has yielded promising results for several neurological diseases, such as Huntington’s disease and amyotrophic lateral sclerosis. In recent years, studies using iPS cells for modelling retinal diseases have gained momentum, including for Best disease and retinitis pigmentosa.
Using iPS cell as a disease model, we can then use them for drug discovery. The current process of drug discovery is very expensive (>$1 billion in development cost), tedious (>10 years) and highly unsuccessful with only 1-5 per cent of drugs transitioning from the laboratory to the clinic. One of the reasons for this is often due to the lack of good clinically-relevant disease models for drug testing. In this regard, disease-specific iPS cells allow us to screen and test multiple drugs to correct the disease in the affected cell types. This could potentially lead to identification of novel drugs to improve treatment options and fast-track the process of drug development. iPS cells will also advance the development of ‘personalised medicine’, as drugs can be tested in diseased cells generated from the patient themselves and tailored to better suit individual needs.
Finally, for diseases where the affected cells are ‘damaged beyond repair’, iPS cells offer the potential for cell replacement therapy. This refers to transplantation of healthy cells to replace the degenerated cells caused by the disease. Given that iPS cells are generated from the patient’s own cells, there is a minimal risk of immune-rejection for iPS cell derivatives following transplantation. For inherited diseases, cell replacement therapy can potentially couple with gene therapy to correct the genetic defects in the diseased cells prior to transplantation. Currently, Advanced Cell Technology (USA) is conducting a clinical trial on cell replacement therapy for Stargardt’s disease and Age-related Macular Degeneration (AMD), using retinal pigmented epithelial cells derived from human embryonic stem cells (another type of pluripotent stem cells that are very similar to iPS cells). In addition, Japan will soon conduct a clinical trial for using iPS cell-derived retinal pigmented epithelial cells for treating AMD. These are very exciting times for stem cell research.
Here at the Centre for Eye Research Australia, we aim to harness the potential of iPS cells for treating eye diseases. Our research team is currently generating patient-specific iPS cells and establishing well-characterised and efficient protocols for differentiation into various types of eye cells (in particular retinal cells) that would be suitable for drug screening, disease modelling and potentially, transplantation.
Although the research with iPS cells is still at an early stage and there are many obstacles we need to overcome before their medical potential can be realised, I truly believe that pluripotent stem cell research is a game-changer in our fight against vision loss and blindness. I am very excited and motivated to work with pluripotent stem cells, and I hope that one day, my research could potentially lead to better treatment for patients with eye diseases.
Our research is kindly supported by the NHMRC, University of Melbourne, Ophthalmic Research Institute of Australia, Peggy & Leslie Cranbourne Foundation, Jack Brockhoff Foundation and National Stem Cell Foundation of Australia.