Paul Fairchild

Exploring the interface between immunology and regenerative medicine

Although the dramatic increase in life expectancy over the past century is arguably one of medicine’s greatest successes, it is also responsible for the rising incidence of chronic and degenerative diseases throughout the developed world. The properties of induced pluripotent stem cells (iPSC) offer an attractive strategy to address some of the health-care needs that the current trend in ageing has created. Nevertheless, the use of these cells in cell replacement therapy faces many challenges including their immunogenicity, which threatens to undermine the success of regenerative medicine in the future.

Teratoma tissue showing CD4+ T cells (red), many of which express of Foxp3 (blue).

Colony of iPS cells expressing of pluripotency genes.

One aspect of research in the laboratory is to investigate the nature and extent of the immunological barriers to cell replacement therapy and to develop innovative ways to establish transplantation tolerance to the implanted tissues.

Whereas the issues of immunogenicity remain a significant challenge to the application of iPSC to the treatment of degenerative diseases, their use as a novel source of dendritic cells for immunotherapy may prove more amenable to clinical translation since their administration to recipients may achieve a lasting immunological effect that is not dependent on their long-term survival. We therefore seek to exploit the unique opportunities that iPSC bring to the field of immunotherapy by making accessible minor subsets of dendritic cells, previously available only in trace numbers. Having recently reported the differentiation of the CD141⁺XCR1⁺ subset from human iPSC, we are exploring how their unique capacity for the cross-presentation of exogenous antigens makes them attractive candidates for downstream clinical applications. These applications include cancer vaccination, the clearance of residual reservoirs of HIV-1, and the induction of tolerance to therapeutic proteins such as the enzymes required for treatment of the lysosomal storage diseases.