Harnessing the power of cell therapy
Home / R&D / Next generation therapeutics / Cell therapies
What is cell therapy?
Cell therapy refers to placing new, healthy cells into the body to replace diseased or damaged ones, to modulate the function of the patient’s cells through expression of factors or direct interaction, or the removal of disease causing or dysfunctional cells using immune cells.
Using cell therapy to halt and reverse disease, restore damaged organs, and, ultimately, cure many life-threatening conditions is now a realistic goal for our scientists, who are working at the cutting edge of regenerative medicine. Important advances in the understanding of disease biology and major innovations in gene editing, protein engineering and cell culture technology have created a highly fertile scientific environment in which cell therapy research is flourishing.
Jump to section:
- How are stem cells used in cell therapy?
- What is CAR-T cell therapy?
- Reversing the effects of kidney damage
- Restoring liver function using human biliary epithelial cells
- New muscle for failing hearts
- Stabilising T cells to combat autoimmune diseases
- Using cutting-edge technology
- Collaborations
- Join us: Working together to advance cell therapy
How are stem cells used in cell therapy?
Stem cells are special cells that are able to differentiate into almost any type of cell in the body. In cell therapy, stem cells or their derivatives are used to generate new tissue or promote the repair response in injured cells. Our scientists hope to one day be able to use stem cells to repair failing organs and avoid the need for transplantation of donor organs.
Our strategy involves exploring the regeneration of tissues and organs using either a patient’s own cells or donor derived ‘off-the-shelf’ cells that can be given to any patient to reverse and potentially cure life-threatening diseases. For example our skills in directing differentiation of multi-purpose, pluripotent stem cells into precursors of heart muscle cells and cells that form the ‘scaffold’ of multiple tissues is opening the door to novel therapies for heart failure, kidney and liver diseases.
What is CAR-T cell therapy?
We are exploring the removal of disease causing or dysfunctional cells using engineered immune cells, such as CAR-T.
Advances in our understanding of the immune system is also informing the development of new therapies across a range of tumour types in oncology. Our approach looks to find new ways to amplify the immune system’s capacity to recognise and eradicate undesirable cells in patients, such as tumour cells. This could provide a novel treatment option to effectively target specific disease-causing cells while leaving healthy cells unaffected.
In addition, in immunology, our research is also aimed at stabilising regulatory T cells (Treg cells) to prevent overactive immune responses which have the potential to transform the treatment of a wide range of immune-mediated diseases.
Reversing the effects of kidney damage
Repairing or replacing damaged kidney tissue has the potential to reverse and cure life-threatening chronic kidney disease (CKD) and the associated life-changing consequences of dialysis and the distressing wait for a transplant.
We are applying our expertise in producing miniature kidneys (kidney organoids) for testing new drug modalities and exploring the tantalising prospect of growing kidney organoids as a cell therapy option for CKD.1-3 Our collaborator, Professor Kenji Osafune, Department of Cell Growth and Differentiation, CiRA and board member of Rege Nephro, has succeeded in establishing a technology to efficiently produce kidney progenitor cell types from human induced pluripotent stem cells.4,5 Together, we are exploring applying this technology to realise the potential of kidney regenerative medicine – an approach arousing considerable interest among our researchers committed to improving the outlook for patients with CKD.
Restoring liver function using human biliary epithelial cells
Biliary cells make up less than 5% of the liver but are vital to drain away toxins. When biliary cells are damaged, the whole liver can fail. Current therapies are rarely effective and at best only slow disease progression. Eventually, if the liver becomes severely damaged, liver transplantation is the only option for patients; however, given the shortage of organs, this is not always a possibility.6
Our researchers are striving to find new cell therapies for liver disease. In collaboration with the University of Edinburgh Institute for Regeneration and Repair, we are exploring the potential of human biliary epithelial cells as a therapy for biliary disease. Early research demonstrates that when transplanted, these cells have the potential to mediate repair, reduce scarring and restore biliary structure and function. This could offer a potential new cell therapy to treat life-threatening liver disease and offer a vital alternative to liver transplants.7
New muscle for failing hearts
Up to one billion heart muscle cells may die as a result of reduced blood supply during a heart attack.8 This can lead to debilitating and often fatal heart failure.
Our researchers, in collaboration with Swedish biotech company Procella Therapeutics and the Karolinska Institute, are determined to change that.
We have successfully differentiated stem cells into human ventricular progenitor (HVP) cells that are capable of forming new cardiac tissue. In preclinical research, we have seen how these HVP cells, when injected in into a damaged heart, engraft, proliferate and develop into beating ventricular cardiomyocytes like those in a healthy heart, leading to improved cardiac function.9
We have also seen encouraging anti-fibrotic activity after HVP injections.10 This is important as scar tissue arising from fibrotic changes is typically seen after a heart attack, and reduces normal heart function.
This research could help us achieve our ambition to form new cardiac tissue via remuscularisation of the heart so that we can cure patients with heart failure.
Stabilising T cells to combat autoimmune diseases
Re-balancing the immune system in people whose immune cells mistakenly attack other cells in their body has great potential for innovative, long-term treatments for a wide range of immune-mediated diseases such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) and rheumatoid arthritis.
A major focus of our immune cell therapy research focuses on regulatory cells, such as Treg cells, which act as ‘natural brakes’ in the immune system and control the activity of other immune cells.11 In immune-mediated diseases, Treg cells are outnumbered or lose control, shifting the balance towards destructive immune cells that attack healthy tissue.
As part of our research into novel treatments for patients with immune-mediated diseases, we will investigate how to effectively expand and stabilise regulatory cells in the laboratory so that when they are reinfused into patients, they take back control and prevent the destructive effects of other immune cells.12 Over the next five to 10 years we hope to see ‘off-the-shelf’ functionalised Treg cells moving into clinical trials as next generation therapies, helping to address the current great unmet need in patients with immune-mediated diseases.
Using cutting-edge technology in cell therapy
Our scientists are applying an array of cutting-edge technologies to drive important advances in cell therapy. These include gene editing to create ‘universal cells’ that can be given to any patient, and antibodies to target our cell therapies where they are needed most.
In patients with heart or kidney failure, universal cells offer the potential for ‘off-the-shelf’ cell therapy without the need for immunosuppressant drugs to prevent rejection. In autoimmune diseases, infusions of universal Treg cells could replace the need to extract T cells from each patient’s blood, process and reinfuse them. Similarly, the use of engineered T cells in Oncology could potentially allow physicians access to a range of patient-ready therapies developed from healthy donors.
To enable our cell therapies to reach the precise area in the body where they are needed, we will attach antibodies that recognise target tissues and can guide our cell therapies into position. There is also the potential to equip cell therapies with ‘self-destruct’ switches so that if they are no longer needed, they can be removed.
Accelerating cell therapy development through collaborations
We are building exciting collaborations with leading scientific and medical institutions, and commercial partners around the world to address key challenges in cell therapy and drive progress.
Kyoto University and Rege Nephro
Induced pluripotent stem cells represent a promising therapy for treating kidney diseases. We are collaborating with Center for iPS Cell Research and Application (CiRA) Kyoto University and Rege Nephro to develop a new method of producing kidney organoids from renal progenitor cells, analysing their developmental biology and physiological functions in-vivo.
Medical Research Council (MRC)
We are co-funding a postdoctoral fellowship scheme with the MRC to support research into key topics relating to cell therapy including patient safety, delivery in the human body and interactions with the immune system. The scheme will enable early career researchers to undertake an academically-led independent research project, improving health outcomes, training the next generation of scientists and fostering collaborations between academia and industry.
Monash University
Building on recent research from the Australian Regenerative Medicine Institute (ARMI), part of Monash University, we are exploring the role of macrophage-based technologies for tissue regeneration. Our work seeks to better understand the role of macrophages in mediating cellular regeneration and will explore whether macrophage-derived signals for muscle stem cells can be applied as new therapeutic modalities for skeletal muscle injuries and degenerative chronic diseases.
Procella Therapeutics
Working alongside Swedish biotech company, Procella Therapeutics, we are exploring the potential of human ventricular progenitor cells to create new cardiac tissue, prevent scar tissue production, and improve cardiac function. This cell therapy research has exciting potential to bring out a new wave of cardiovascular treatment that could reverse damage from heart failure.
University of Edinburgh Institute for Regeneration and Repair
We are collaborating with The University of Edinburgh Institute for Regeneration and Repair to study and develop primary human biliary progenitor cells (HBPs) as a novel regenerative therapy for liver diseases, including multiple cholangiopathies. This important collaboration will enable us to combine our capabilities and expertise to accelerate the development of this potentially lifesaving therapy for liver disease patients who have limited treatment options.
Join us: Working together to advance cell therapy
We welcome committed, talented cell therapy scientists to join us on what promises to be one of the most exciting, stimulating and rewarding journeys in 21st century medicine. We are uniquely positioned to develop the best novel cellular therapies, and we are already growing a differentiated pipeline to address a range of diseases associated with significant unmet need. By giving our people the resources and support to push the boundaries of science, we are going beyond the ordinary to help improve billions of lives worldwide.
We recruit scientists with relevant expertise to join us in our new state-of-the-art research facilities in Gothenburg, Sweden, Cambridge, UK, and Gaithersburg, US. In addition we operate joint post-doctoral programmes in cell therapy with leading academic institutions including the University of Cambridge and Imperial College London which help to drive disease understanding and accelerate drug discovery.
We are proud of our progress, prepared for the challenges that lie ahead, and confident that, in the next five to 10 years, cell therapy will help improve the outlook for patients with some of today’s most serious and life limiting diseases. Find out more about joining us.
References
1. van den Berg CW, et al. In vivo assessment of size-selective glomerular sieving in transplanted human induced pluripotent stem cell–derived kidney organoids. J Am Soc Nephrol. 2020;31:921-929.
2. Jager KJ, et al. A single number for advocacy and communication—worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803-5.
3. Bikbov B, et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study. Lancet. 2017;395(10225):709–33.
4. Tsujimoto H, et al. A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells. Cell Reports. 2020 Apr 7;31(1):107476. doi: 10.1016/j.celrep.2020.03.040.
5. Mae SI, et al. Expansion of Human iPSC-Derived Ureteric Bud Organoids with Repeated Branching Potential. Cell Reports. 2020 Jul 28;32(4):107963. doi: 10.1016/j.celrep.2020.107963.
6. University of Edinburgh – Institute for Regeneration and Repair, Centre for Regenerative Medicine. Press Release: 8 March 2022. Available at: http://www.ed.ac.uk/regenerative-medicine/news-events/latest-news/human-liver-cells-could-treat-biliary-disease
7. Hallett JM, et al. Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease. Cell Stem Cell. 2022;29(3):355-371.
8. Shadrin IY, et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat Commun. 2017 Nov 28;8(1):1825. doi: 10.1038/s41467-017-01946-x.
9. Foo KS, et al. Human ISL1 + ventricular progenitors self-assemble into an in vivo functional heart patch and preserve cardiac function post infarction. Mol Ther. 2018;26(7):1644-1659.
10. Schneider C, et al. Primate heart regeneration via migration and fibroblast repulsion by human heart progenitors. bioRxiv. 2020. doi: http://doi.org/10.1101/2020.07.03.183798
11. Bednar K, et al. Tregs in Autoimmunity: Insights Into Intrinsic Brake Mechanism Driving Pathogenesis and Immune Homeostasis. Front. in Immunol. 2022; 13:932485. DOI: 10.3389/fimmu.2022.932485
12. Ding M, et al. A phenotypic screening approach using human Treg cells identified regulators of forkhead box p3 expression. ACS Chem. Biol. 2019;14:543−553
Veeva ID: Z4-55028
Date of preparation: June 2023