Research and Development Projects
The research arm of The Griffin Institute is working on two areas of potential benefit to people living with Inflammatory Bowel Diseases (IBD) by creating a replacement bowel tissue for transplantation and by developing an in vitro platform for evaluating candidate drugs for the treatment of those patients who are not suitable for surgery. Our tissue engineering approach could also be used to treat other bowel diseases including reconstructive surgery after cancer removal.
Approximately 50% of patients with Crohn’s disease and 20% with UC will require life-changing surgery that involves removal of part of the bowel resulting in complications with stool frequency, malnutrition and infections. As a proof of concept, we will grow stem cells on a biological inert scaffold in the laboratory to optimise the conditions for seeding the patient’s own stem cells for eventual transplantation. Use of the patients own stem cells avoids immune rejection.
This proof of concept will lay the foundation for translational studies and eventual clinical trials for the management of UC and other bowel conditions in man. We also hope that this work will lead to the development of a 3D model where the model tissue populated with healthy cells will be used to better understand the natural progression of UC for the purposes of testing interventions for early stage disease.
The market for skin replacements has developed rapidly in the last few decades to incorporate various dermal scaffolds of both biological origin and artificial design used as provisional matrices to fill the wound void and integrate into the surrounding tissue. These scaffolds are designed to be biodegradable and replaced by the structural proteins, vasculature and resident cells as found in un-injured tissue. Biological scaffolds have the advantage of retaining extracellular matrix (ECM) features unique to the tissue type and essential for regeneration. The Griffin Institute has been at the forefront of developing such matrices from decellularised dermis. In the current realignment of the wound healing studies, we have the opportunity to use the in-house dermal paste, as additional intervention to maximise the chances of a successful healing of the so called ‘non-healing wounds’.
Dermal Paste: Commercially available dermal replacement as sheets do not adequately cover deep wounds. We therefore developed a porcine dermal paste that that has been shown to expedite wound closure and is projected to have better clinical outcomes when supplemented with autologous cells, resulting in fewer surgical procedures involving wound debridement and grafting sessions.
- Non-healing wounds (e.g. varicose ulcers, neuropathic ulcers, diabetic foot ulcers)
- Surgical wounds (e.g. after skin cancer resection)
- Pressure ulcers
- Minimally invasive treatment for fistulae.
Liver organoid units (OU) as a valuable tool for drug screening and target identification in hepatic disorders
Hepatic organoid units are miniature liver-like self-replicating structures grown from cells isolated from liver biopsies. They can be expanded in vitro for long time without losing their phenotype and are suitable for testing candidate drugs and identifying new therapeutic targets in hepatic diseases.
Traditionally, drug safety testing is performed in animals, assuming a similar pharmacological response when it gets to humans. These in vivo tests are prohibitively expensive and unethical for the industrial scale high-throughput screening of several molecular candidates annually. On the other hand, most in vitro 2D models such as the primary human hepatocytes (PHH) and simple cell lines such as HepG2 cells do not give a true representation of the phenotype in vivo. Innovative organotypic in vitro 3D models such as the organoid have emerged to fill this gap and also fit within the 3Rs remit for experimental design (Reduce, Refine and Replace).
At the Griffin Institute, we have developed an in vitro culture of liver organoids and are now in the process of a detailed characterisation in order to use them as a platform for drug development. Selected drug entities will then be tested to explore their pharmacological and toxicological effects on the organoids and validate the method.
– in vitro screening platform to investigate candidate drug therapies
– in vitro model to understand the intrinsic repair mechanisms within the liver in order to promote healthy regeneration.
– Disease model to identify therapeutic targets in the management of chronic hepatic diseases.
– Platform technology for producing functional tissue to be implanted in vivo.