Understanding natural processes of tissue repair to identify targets for new therapies

The central goal of regenerative medicine is to repair or replace damaged or diseased tissue and consequently this has the potential to transform how we treat diseases.  This theme aims to understand the natural processes of tissue repair and to identify targets for new therapies, either via the transfer of stem cells or with small molecules or biologic treatment.

The ability to obtain stem cells from patients and to differentiate them into a range of cell types is key to both understanding disease-specific mechanisms in that patient and testing targeted therapeutics for that patient. This is the basis of precision medicine and is a transformative technology that we will bring to bear on the diagnosis and treatment of multiple diseases that continue to burden our society.

Our work is covered by three programmes:

  • Programme 1. Improved cell transplantation.
  • Programme 2. Harnessing the immune system for regenerative medicine.
  • Programme 3. In vitro approach to precision medicine

Example projects

  • Fibroblasts Fibroblasts are a type of cell found in skin, tendons and other connective tissue in the body.  They are responsible for making collagen and the extra cellular matrix and play an important role in wound-healing.  We have established that a particular sub-type of fibroblast cells, if expanded in population and injected back to the skin, may provide a therapeutic effect in a variety of skin disorders. Research is now being undertaken to develop the manufacturing process for a first-in-human trial for this therapy to treat scarring.

 

  • Bridging strategies in acute liver failure Acute liver failure (ALF) in children has a high mortality rate. Although treatable with liver transplantation there is a shortage of suitable donors and transplantation brings its own risks as a major surgery with life-long immunosuppression.  A previous study in 8 children showed that liver cells (hepatocytes) from deceased donor livers encapsulated within alginate beads (to protect the cells from the patient’s immune system) could provide children with liver functions, either while their own liver regenerated or until they received a liver transplant (Dhawan A, et al., (2020). J Hepatol. 72(5):877-884). A new trial will explore whether encapsulating hepatocytes with mesenchymal stromal cells will improve the function and survival of the hepatocytes. We will also explore whether functional hepatocytes can be derived from stem cells rather from deceased donors.

 

  • Stem cell derived photoreceptor transplantation Inherited retinal disease and age related macular degeneration (AMD) are major causes of irreversible blindness in the UK and involve the loss of photoreceptor cells. We have shown that we can differentiate photoreceptor cells from stem cells and when transplanted into model systems these restore vision (Ribeiro J et al. (2021) Cell Reports 35(3):109022). Working BRC’s Advanced Therapies Manufacturing Unit, our next goal is to manufacture cells to the highest standards which can be used in a human clinical trial. Ultimately, we seek to develop a treatment for age-related macular degeneration which results from the loss of RPE as well as cones and would need co-transplantation of both cell types in conjunction with the use of biomaterials to form a small retinal patch.