Organizational profile: UK Regenerative Medicine Platform Immunomodulation Hub
Free to access Organizational Profile from the Regenerative Medicine Special Focus Issue
The UK Regenerative Medicine Platform was launched in 2013 as a jointly funded venture by the Biotechnology and Biological Sciences Research Council (BBSRC), Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC) to address the technical and scientific challenges associated with translating promising scientific discoveries into the clinical setting. The first stage of the Platform involved the establishment of five interdisciplinary and cross-institutional research Hubs and the final Hub, the Immunomodulation Hub, was formed in 2014. The Immunomodulation Hub comprises scientists from diverse clinical and nonclinical research backgrounds. Collectively, they provide expertise in tissues for which there is an unmet clinical need for regenerative treatments, in innate and adaptive immunity and in whole organ transplantation. Their vision is that by working together to determine how regenerative medicine cell therapies in a laboratory setting are affected by the immune system, they will make a substantial contribution to long-term clinical deliverables that include improved efficacy of photoreceptor cell therapy to treat blindness; improved repair of damaged heart tissue; and improved survival and functionality of transplanted hepatocytes as an alternative to liver transplantation.
By Curtis Asante, UKRMP Immunomodulation Hub Project Manager.
Professor Fiona Watt, Centre for Stem Cells & Regenerative Medicine, King’s College London
My major research interests are focused on the role of stem cells in adult tissue maintenance and recently, my lab showed that skin fibroblasts comprise distinct lineages with different contributions to wound healing. By liaising with other members of the hub, we are addressing whether or not different subsets of fibroblasts identified in mouse skin have immunomodulatory properties. This is being achieved by performing gene expression profiling on different fibroblast populations, in order to identify the immunomodulatory genes they express and to examine whether this correlates with specific cell signaling pathways that are known to be implicated in modulating immune cell responses. I am also liaising with other members of the hub to address whether or not different fibroblast lineages identified in the skin also exist in other tissues such as the heart, eye and intestine. If the fibroblast lineages are present, as suspected, we will then study how they respond to inflammation and repair by examining their role in mouse models of human disease.
Autologous fibroblast transplantation is already being evaluated for its potential in promoting the healing of acute wounds and the repair of scarred skin tissue. We anticipate that outside of these applications, partly due to the work being carried out in the Immunomodulation Hub, we will have a much better understanding of the therapeutic potential of fibroblasts in a variety of tissues.
Professor Robin Ali, UCL Institute of Ophthalmology, Gene & Cell Therapy Group
The main aim of our work is the development of photoreceptor cell transplantation to repair the retina following retinal degeneration. We have shown previously that transplantation of rod photoreceptor precursor cells into the adult mouse retina results in integration and differentiation into rod photoreceptors that form synaptic connections and can improve vision in mouse models of visual dysfunction. We have also differentiated and transplanted mouse embryonic stem cell-derived photoreceptor precursors into animal models of retinal degeneration. While our studies provide the first proof- of-concept for effective transplantation of neurons and provide the foundations for human pluripotent stem cell-derived photoreceptor transplantation, we have also shown that host immune responses reduce the long-term survival of the transplanted cells. Within the Immunomodulation Hub we are working to characterize in detail the recipient immune response toward transplanted retinal cells and to develop immunomodulatory strategies to prolong the survival of transplanted cells within the retina.
Successful cell therapy for retinal degeneration will require immunomodulation to increase long-term cell survival. By understanding recipient immune responses, we will be able to develop an effective strategy to modulate responses locally in the retina and thus avoid serious adverse events associated with systemic immunosuppression.
To read what research all the members of the Immunomodulation Hub are doing, please have a look at the full, free-to-access profile here.