With the ageing population, regenerative medicine is growing in both interest and importance. The SingHealth Duke-NUS Cell Therapy Centre shares how ongoing research and innovation promises to improve medical treatments and patient outcomes.
With the ageing local and global population, regenerative medicine is growing in both interest and importance. From heart and eye diseases to Alzheimer's, find out how the ongoing research and innovation work at the SingHealth Duke-NUS Regenerative Medicine Institute of Singapore (REMEDIS) promises to improve medical treatments and patient outcomes.
INTRODUCTION
What is regenerative medicine?
Regenerative medicine is the science of developing therapeutics and tools to restore diseased tissues and organs.
It includes gene therapies, cell therapies, tissue engineered products and small molecules intended to augment, repair, replace or regenerate organs, tissues, cells, genes and metabolic processes in the body.
Why is it important?
Regenerative medicine is of particular importance to the ageing global population. In Singapore, the median population age has doubled over the last five decades, leading to an increase in age-related diseases of the heart, neurons and eyes, and even cancers.
Effective and accessible clinical care for these debilitating age-related conditions could also mean savings of billions of dollars that would otherwise be used to foot the bills for chronic medical care and work productivity losses.
A Hub of Regenerative Medicine: The SingHealth Duke-NUS Regenerative Medicine Institute of Singapore (REMEDIS)
The SingHealth Duke-NUS Regenerative Medicine Institute of Singapore, otherwise known as REMEDIS, was established at the SingHealth Duke- NUS Academic Medical Centre as a global centre of excellence for basic and translational research in regenerative medicine.
Singapore is equipped with extensive multidisciplinary research hubs and clinical infrastructure that are essential for cutting-edge research in regenerative medicine. By consolidating and focusing these resources through the establishment of REMEDIS, Singapore could soon be at the forefront of innovating and delivering regenerative medicine products to patients in the region and beyond.
REMEDIS will work towards its vision of 'Restoring Function and Embracing Life' in collaboration with multidisciplinary research hubs and local clinical groups.
Areas of focus for REMEDIS include regenerative therapies for:
- Ischaemic heart disease
- Sarcopenia
- Neurodegenerative diseases (e.g., Alzheimer's and Parkinson disease)
- Age-related eye diseases
- Bone marrow disorders
- Burns
Ongoing work by REMEDIS to advance regenerative medicine includes:
CARDIOVASCULAR REGENERATION FOR CARDIOMYOPATHY
The Cardiovascular Regeneration Programme focuses on heart disease, an important cause of mortality and morbidity.
Professor Tryggvason of Duke-NUS Medical School and his team have established the use of extracellular matrix proteins to grow human cardiomyocytes from pluripotent stem cells.
These cardiovascular progenitors, when implanted in pigs with myocardial infarction, rescued infarcted hearts, functioned normally and most importantly did not cause ventricular arrhythmia, a common problem in other competing technologies.
The team has obtained a grant from the National Research Foundation to translate these therapies to clinical applications with clinicians from the National Heart Centre Singapore. If successful, this could reduce the need for heart transplantation, which is limited due to the lack of donors.
SKELETAL MUSCLE REGENERATION FOR SARCOPENIA
The Skeletal Muscle Regeneration Group focuses on sarcopenia, a skeletal muscle wasting disease, which is a poorly understood threat to the health span, mobility and quality of life of the ageing population. There is currently no cure.
The team has successfully identified a cause and potential treatment for sarcopenia associated with cancer and now sets its sights on addressing skeletal muscle wasting associated with ageing and other diseases like liver cirrhosis and renal failure.
NEURAL REGENERATION FOR ALZHEIMER'S AND PARKINSON DISEASE
Professor Zhang Suchun of Duke-NUS Medical School is a leader in successfully generating different types of healthy neurons from pluripotent stem cells that could be used to replace diseased neurons.
Dr Tan Eng King of the National Neuroscience Institute has also pioneered the use of stem cells to treat Parkinson disease. While much of this research is still in the pre-clinical stage, success could lead to new treatments for Alzheimer's and Parkinson disease.
EYE REGENERATION FOR AGE-RELATED EYE DISEASES
Sight is probably the most powerful sense of the human body. Unfortunately, there are at least 2.2 billion people worldwide who have impaired vision or blindness. The majority are over the age of 50.
The two leading causes of age-related blindness are Fuchs' endothelial corneal dystrophy and age-related macular degeneration.
Professor Jodhbir Mehta of the Singapore National Eye Centre has pioneered a robust culture system for human corneal endothelial cells to treat age-related corneal blindness, and was also the first to identify the location of corneal endothelial progenitors. In addition, the team of scientists has developed and patented a novel photoreceptor differentiation method.
BONE MARROW REGENERATION FOR BLOOD CANCERS
Bone marrow failure can occur because of ageing, genetic conditions, immune dysfunction or as a preleukaemia disorder. It is usually thought of as a hematopoietic stem cell disease.
Singapore is the regional referral centre for hematopoietic stem cell transplants, which is a standard of care for complex blood cancers. Slow recovery of blood counts after transplantation gives rise to complications, increased medical bills and treatment failures.
We have participated in international clinical trials on blood stem cell expansion which have shown good efficacy in accelerating blood cell count recovery after transplantation, resulting in fewer infections and shorter hospitalisation.
Our team at Singapore General Hospital (SGH) has also embarked on a new clinical trial on cord blood stem cell expansion using novel technology developed by SGH, Duke-NUS Medical School, the National University of Singapore and the National Cancer Centre Singapore. Success in this trial would mean that patients could undergo cord blood stem cell transplants with significantly reduced complications.
WOUND REGENERATION FOR TREATMENT OF SEVERE BURNS
According to the World Health Organization, burns are a global public health problem, accounting for an estimated 180,000 deaths annually.
Non-fatal burns are a leading cause of morbidity vis-a-vis prolonged hospitalisation, disfigurement and disability, often leading to stigma and rejection. It was estimated in 2004 that nearly 11 million people worldwide were burned severely enough to require medical attention.
Methods for treating severe burns have changed in recent decades, and an increasingly aggressive surgical approach with early excision and wound closure is advocated to reduce infection and improve mortality. Surgeons now face the challenge of excising and grafting larger burns of more than 50% of the total body surface area with limited skin availability.
Thus, it is imperative to find skin substitutes to supplement conventional split-thickness skin autografting. While cadaveric skin allografting provides wound coverage, it is temporary owing to tissue rejection after two to three weeks. In addition, there are limited supplies of skin allografts harvested from deceased donors.
Cultured skin, which is the expansion of autologous epithelial cells and their progenitors isolated from a small skin biopsy, is a potential solution for obtaining large amounts of epithelial cell sheets to treat extensive burns.
At the SGH Skin Culture Lab, we are harnessing the inductive properties of extracellular matrix to optimise epidermal stem cell growth. This is accomplished in a safe and well-defined microenvironment that complies with the standards of Good Manufacturing Practice.
We are also studying non-native sources of immunoprivileged epithelial cells, such as the umbilical cord lining for skin tissue engineering applications.
CONCLUSION
Important discoveries have helped to improve our understanding of how organs and tissues degenerate. This could lead to the development of new tools, diagnostics and therapies for organ and tissue regeneration. Patients will have a lot to look forward to with regenerative medicine due to exciting new developments in science, infrastructure, developmental tools and clinical trials.
Professor William Hwang is Medical Director of the National Cancer Centre of Singapore, Head of the SingHealth Duke-NUS Cell Therapy Centre, Chair of the Oncology Academic Clinical Programme at Duke-NUS Medical School, and Senior Consultant at the Department of Haematology, Singapore General Hospital. He is also an Executive Board Member of the Asia Pacific Blood and Marrow Transplantation Group, as well as a Board Organising Committee member of the Singapore Translational Cancer Consortium and Advanced Cell Therapy Research Institute of Singapore (ACTRIS).
Professor Jodhbir Mehta is a distinguished Professor in Clinical Innovation in Ophthalmology at the Singapore National Eye Centre and the Deputy Executive Director, Head Tissue Engineering and Cell Therapy Group at the Singapore Eye Research Institute. His clinical work is focused on corneal transplantation, anterior segment reconstruction and refractive surgery. He has won 52 awards internationally for clinical and research work, most recently the American Academy of Ophthalmology Senior Achievement Award 2017, Doug Coster Lecture from the Australian Corneal Society 2018, Charles Tillett Lecture 2020 and Casebeer Award 2020.
Professor Karl Tryggvason is a Professor at Duke-NUS Medical School, Singapore, Adjunct Professor at Duke University, North Carolina and Emeritus Professor at the Karolinska Institute, Stockholm. His research concerns the molecular composition, biology and diseases of basement membranes (BM), a special compartment of the extracellular matrix. His group has cloned almost all human BM proteins and clarified genetic causes of many BM-associated diseases, such as Alport and congenital nephrotic syndromes, junctional epidermolysis bullosa and congenital muscular dystrophy.
Professor Teh Bin Tean is the Co-Director of the SingHealth Duke-NUS Regenerative Medicine Institute of Singapore, Deputy Medical Director (Research) at the National Cancer Centre Singapore and Principal Investigator of the Laboratory of Skeletal Muscle Regeneration.
Clinical Professor Tan Bien Keem is a Senior Consultant at the Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital (SGH), where he is also the Programme Director of the Skin Bank Unit. Prof Tan has served as Deputy Director, Cell and Tissue Transplantation at the SingHealth Duke-NUS Transplant Centre since January 2015. He is also a member of the Advisory Committee on Transplantation at SGH, a member of the SingHealth Duke-NUS Surgery Academic Clinical Programme and Associate Editor for the Archives of Plastic Surgery Journal.
Clinical Associate Professor Alvin Chua is Assistant Director (Transplant Research) and Principal Investigator of the Plastic, Reconstructive & Aesthetic Surgery Research Laboratory at Singapore General Hospital. He is also the Regulatory & Compliance Lead for the SingHealth Duke-NUS Cell Therapy Centre as well as Assistant Director of the Transplant Tissue Centre at the SingHealth Duke-NUS Transplant Centre, where he is responsible for the regulatory compliance, operations, quality assurance and research of tissue transplantations for skin, cardiovascular tissues and iliac vessels.
GPs can contact the SingHealth Duke-NUS Cell Therapy Centre at sd.cell.therapy@singhealth.com.sg to know more about the available cell therapies and clinical trials on the SingHealth campus, or scan the QR code for more information.
