Cells, tissues and organs can be used as models to study disease or used themselves as therapeutics for (chronic) diseases, through for example transplantation. The Theme Cells, Tissues and Organs (CTO) covers both approaches, the ultimate aim being to resolve unmet clinical needs.
Vision and mission
Over the next 5 years, our ambition is to develop the CTO Theme to deliver new therapies Regenerative Medicine at LUMC. Clinician scientists interacting closely with and inspired by basic scientists will advance applications of Regenerative Medicine in tissue and organ repair. We will adapt and combine cells, including stem cells, and biomaterials for direct transfer to patients. In addition, we will use them as personalised or disease specific models to identify drugs and gene therapies for precision medicine.
Original and collaborative thinking
Creating ecosystems that facilitate original and collaborative thinking will support better grant proposals, publications, visibility and overall output on the Theme’s topics and ultimately benefit patient health. Better alignment of LUMC clinicians with basic scientists will optimise the valorisation of our research.
For all CTO Theme applications, cells, tissues and organs for transplantation and other therapeutic strategies need to be appropriately defined and their application validated before use. Other therapeutic strategies include drug and gene discovery based on known disease mechanisms or signalling pathways. Besides, regulatory and other procedures need to be correctly followed in moving to clinical trials. The LUMC already has experience in this area but sharing knowledge and expertise with other Themes for Innovation at the LUMC, such as Academic Pharma, can accelerate implementation.
“We have a strong profile in human pluripotent stem cell research, combined with complementary capabilities in cell production and functional readouts and a track record in clinical translation of cell therapies. This means that the LUMC is well-placed to deliver novel models for human disease and the next generation of hiPSC based therapeutics to patients.”- Christine Mummery
Christine Mummery, Professor of Developmental Biology
Christine Mummery is Professor of Developmental Biology at Leiden University Medical Center and an expert on pluripotent stem cells. She became guest professor at the University of Twente in 2015 to use stem cells in organ-on-chip models. In 2017, she led an NWO Gravity consortium to carry out this research nationally. She has also received ERC-Advanced and Proof-on-Concept grants. She is a member of the Royal Netherlands Academy of Science and Academia Europaea. She wrote the lay-guide Stem Cell: Scientific Facts and Fiction and is Founding Editor-in-Chief of Stem Cell Reports, the journal of the International Society of Stem Cell Research.
Ian Alwayn, Professor of Transplant Surgery
Ian Alwayn is Professor of Surgery, in particular Transplant Surgery. He is also Head of the Transplant Surgery sub-department of the LUMC and chairman of the management team of the LUMC Transplantation Center. He has received grants for his research from, among others, the Netherlands Organization for Scientific Research (VENI), Canadian Institution of Health Research, Canadian Foundation for Innovation, Nova Scotia Health Research Foundation and the Dutch Kidney Foundation.
Françoise Carlotti, Associate Professor
Françoise Carlotti is Associate Professor and Head of the Islet Research lab. Her research interests focus on investigating mechanisms underlying pancreatic beta-cell adaptation and cellular plasticity, and on alternative sources of insulin-producing cells for beta-cell replacement therapy. As principal investigator (PI), she obtained research funding among others from JDRF, the Dutch Diabetes Research Foundation, DON foundation, and the European Foundation for the Study of Diabetes. She is a PI in the Dutch initiative RegMed XB, and in the H2020 European consortia ISLET and ESPACE.
Research collaborations and alliances
If you would like to collaborate or seek specific expertise and do not know where to start, please contact us and we will connect you.
For PhDs and Postdocs
If you are looking for a position within the Cells, Tissues and Organs Theme or are near the end of your contract and interested in opportunities elsewhere, please contact us.
Please contact the Cells, Tissues and Organs Theme leaders if you are looking for an internship. We generally recommend a minimum internship period of 6 months since learning about the cell culture technology required for research requires sufficient training time.
Read more about our topics and scientists
Cells, tissues and organs can be used as models to study disease or used as therapeutics for (chronic) diseases, through for example, transplantation. The Theme CTO includes both approaches as its research focus, with the ultimate aim to resolve unmet clinical needs. Research within the theme is divided into three subthemes.
The subtheme Regenerative medicine is divided into Cell therapy and Gene therapy. Cell therapy has the ultimate aim to produce clinical-grade stem cell derivatives and use these to treat conditions of clinical focus within the LUMC. Gene therapy deals with the repair of genetic defects in a patient own cells and can be carried out using various approaches, including viral vectors.
Our subtheme Disease modelling is about stem cells, microphysiological systems (MPS) or Organs-on-Chip that many research groups in the LUMC use to create models for heart, kidney, brain, lung, bone, muscle, liver, eye, ear, blood vessels and skin. In many cases, genetic diseases have been captured by these models and research is underway to find gene or drug therapies.
The LUMC is a leading centre for transplantation, and in our subtheme Transplantation, we build on a long and successful history of bone marrow transplantation and strong transplant immunology expertise. Our main goals are to assess and optimise donor organ, tissue and cell quality before transplantation, to develop novel strategies of targeted intervention in donor and recipient, and to improve patient outcomes on the waitlist and post-transplant.
The human body has the natural ability to heal itself after injury: cuts in the skin, broken bones, and even damaged organs such as the liver can regenerate and repair themselves. However, not all tissues or organs have this capacity. Regenerative medicine aims to develop alternatives to self-repair mechanisms, replacing or restoring damaged cell, tissue or organ function caused by disease or injury. This will bring new solutions for patients across a wide range of medical conditions.
Cell therapy is an approach that relies on the use of cells as therapeutics. For replacement therapy, the therapeutic cells or progenitor cells can be obtained from patients themselves or a donor. These cells can generate a limited number of cell types.
Another option is to use pluripotent stem cells (PSC), which can generate any cell type of the body. Through increasingly well-defined differentiation protocols, multiple cell types of different organs can now be formed in the laboratory. At the LUMC, human PSC are central to many research groups intending to use the cells in therapy, as Advanced Therapy Medicinal Products (ATMPs).
Gene therapy aims to repair genetic defects to restore a dysfunctional or missing protein in a patient’s cells. The therapeutic genetic material (DNA or RNA) is transferred to the target cells in various ways using viral, for example, lenti-, adeno-, adeno-associated viruses, or non-viral, such as liposome, vectors.
As a result, the patient cells can produce the therapeutic protein specific to the disease. The LUMC is at the forefront in the development of several gene therapies, in particular with the first clinical trial worldwide for RAG1 SCID. This genetic disorder that severely compromises the immune system.
Projects Cell therapy
The only cure for end-stage kidney failure at present is kidney transplantation but only relatively few patients can be treated because of the shortage of donor organs. There are currently more than 600 patients on the waiting list in the Netherlands. Generating kidney tissue from stem cells may in the future contribute to Regenerative Medicine solutions for these kidney disease.
Daily insulin injection is currently the most widely used treatment for type I diabetes, although for the most serious and unstable forms of the disease, transplantation of the pancreas or islets of Langerhans are alternatives. However, there is a shortage of donor organs and immunosuppression after donor tissue transplantation has side-effects. Regenerative medicine based on stem cells offers opportunities to develop alternatives.
There are presently few cures for hereditary or age-related forms of blindness. Damage to the cornea and retina can be caused by several diseases, and for some conditions, the incidence increases with age. Regenerative medicine can now offer new opportunities on which to bases cure for some select causes of blindness.
In chronic lung emphysema, the small air sacs called alveoli, are damaged, and this severely impairs breathing in affected patients. Alveolar damage is usually caused by inflammation, and whilst symptoms can be alleviated, the alveoli cannot regenerate. Regenerative medicine holds the promise to restore lung function.
Brain, nerves, muscle
Conditions affecting the brain, spinal cord, nerves and muscles can affect people of all ages. Although, in some cases, the symptoms can be alleviated, there are few cures. In regenerative medicine research, we investigate the cause of these conditions, investigate possible treatments and work towards cures for a small number of specific diseases.
Heart, Cardiovascular, Pericytes
Treatment of heart disease currently involves advice on lifestyle changes such as weight loss or greater activity, medication or surgery. Regenerative medicine could offer opportunities to develop new treatments for various forms of heart disease.
Skin, Vascular system
Burn wounds, cancer and vascular disease can all cause damage to our skin and vascular system. Regenerative medicine research can provide new opportunities for the treatment of these diseases.
Damage to the ovaries, for example, following cancer treatment, invariably leads to loss of fertility as the immature eggs are damaged. For women with damaged ovaries, the normal production and release of eggs cells cannot take place. In the future, it may become possible to make an artificial ovary through regenerative medicine and mature human oocytes outside the body.
Liver and Intestine
Treatment of liver and bowel disease forms part of the clinical speciality Gastroenterology and Hepatology. For the many diseases in these organs, current treatment usually involves advice on lifestyle changes such as restrictions to the diet or alcohol intake, medication or surgery. Regenerative medicine could offer alternatives to treat diseases of the digestive tract, particularly conditions where inflammation is the underlying cause of disease.
Patients with blood cancer or genetic defects in blood or immune cells can be treated by “hematopoietic stem cell” transplantation. Here, the diseased bone marrow of the patient is replaced by healthy stem cells from a donor. Stem cell transplantation, however is associated with the risk of “graft-versus-host disease”, a complication that is often fatal in which immune cells from the donor attack the host’s tissues. Regenerative medicine may provide several new options for treating blood disorders.
Artificial hearing aids in the form of an implanted device is presently the only treatment for many deaf patients. Regenerative medicine may provide ways in which damaged cells in the ear can be replaced. As we work towards a better understanding of underlying causes of hearing loss, we may find new cures for certain forms of deafness in the future.
Bones and joints are permanently damaged in diseases such as osteoarthritis, rheumatoid arthritis, bone tumours and osteogenesis imperfecta. Current treatments mainly treat pain and other symptoms with limited success. Regenerative medicine offers new opportunities for research leading to functional recovery.
Projects Gene therapy
Understanding adult (bone marrow) stem cell biology and T cell development is the basis for developing new therapies for treating haematological and immune system disorders. Advanced molecular and cellular (20+ colour spectral flow cytometry) techniques and mouse genetic models can be used, as well as human cells from patients and healthy individuals for this research. Regenerative medicine endeavours to transition from basic- to translational and clinical research, specifically in preparing for clinical trials.
Viruses are experts at taking over host cells, a process essential for the production of viral progeny. Following infection, major factors that determine the success of a virus in this process are its ability to exploit normal cellular processes and adapt to the host’s anti-viral measures. Regenerative medicine aims to use viral vectors to deliver gene therapy.
Related research facilities
Understanding the molecular and cellular origin of disease through studies on animal- and advanced human cell, tissue and organ models is a major goal of this subtheme. Clinical and basic researchers collaborate with overarching technologies to advance knowledge on why disease affects some individuals more than others.
We also look into why drugs are not effective in all patients or patients become refractive and whether new disease targets can be identified that would lead to novel therapeutic strategies. For this, we need to generate better, as necessary, more complex, in vitro models not only containing cells of the tissue of interest but also blood- and lymph-vessels, inflammatory and immune cells and biophysical constraints. This is necessary, for example, to mimic lung, kidney, heart and muscle, physical stretch and strain under microfluidic flow.
Central in this is the validation of the human disease models and comparison with manifestations of the disease in animal models and patients. The 3Rs (reduction, replacement, refinement) of animal experiments is among LUMC ambitions. However, implementation and acceptance are only realistic if the human models provide at least equivalent or preferably better information on disease mechanisms and targets and are at the same time amenable for screening new therapies.
Disease modelling using human pluripotent stem cells (hiPSC)
The LUMC is a major centre in the Netherlands for the generation of hiPSC lines from patients. These cells can form any cells of the body and have the same genetic make-up as the donor. They can be genetically manipulated, so that genetic mutations can be corrected or disease mutations introduced into a healthy hiPSC line. Protocols have been developed and tested to derive many cell types, including from the heart, brain, blood vessels, cells of the lung, kidney, eye, cartilage or bone, skeletal muscle, pancreas and the reproductive and immune systems. This informs on cell and tissue relevant changes caused by mutations, drugs, toxic compounds, bacteria and viruses. In combination with -omics analyses, (live) imaging and electrophysiology, it helps identify disease targets for phenotypic correction and future therapies.
Creating realistic human tissue mimics using microfluidics
Living tissues in the body are complex 3D structures composed of different cell types, with blood and lymph vessels through which fluids flow. The tissues undergo spatial constraints that result in pressure and load, and in the case of muscle, contraction and relaxation in response to (patho)physiological stimuli. To create realistic tissue models, it is important to include at least some of these parameters. This can be done in Organ-on-Chip devices (OoCs) and the LUMC is one of a few centres in the Netherland specialised in the use of OoCs to address biological questions on human tissue (dys)function based on stem cells. Heart-, lung-, eye-, heart-, brain-, lymph- and blood vessels-on chip are present areas of interest are under development.
Functional analysis of gene therapies
The LUMC has several focus areas in gene therapy that range from novel vectors for delivering gene constructs to mRNA-based approaches. Transgenic mice are used as well as human tissues and (stem) cell models. Diseases include inherited skeletal muscle conditions like dystrophies (based on human cells where mouse models are not available or the gene does not exist), and myopathies of the heart.
Related research facilities
Related research groups