Approaches for immunological tolerance induction to stem cell-derived cell replacement therapies

Abstract

The shortage of donors for organ transplantation and also to treat degenerative diseases has led to the development of the new field of regenerative medicine. One aim of this field, in addition to in vivo induction of endogenous tissue regeneration, is to utilize stem cells as a supplementary source of cells to repair or replace tissues or organs that have ceased to function owing to ageing or autoimmunity. Embryonic stem cells hold promise in this respect because of their developmental capacity to generate all tissues within the body. More recently, the discovery of induced pluripotent stem cells, somatic cells reprogrammed to a primitive embryonic-like state by the introduction of pluripotency factors, may also act as an important cell source for cell replacement therapy. However, before cell replacement therapy can become a reality, one must consider how to overcome the potential transplant rejection of stem cell-derived products. There are several potential ways to circumvent the hurdles presented by the immune system in this setting, not least the induction of immunological tolerance in the host. In this review, we consider this and other approaches for engendering acceptance of stem cell-derived tissues.

Keywords::

• cell replacement therapy
• embryonic stem cells
• immunogenicity
• induced pluripotent stem cells
• regulatory T cells
• stem cells
• tolerance
• transplantation

Financial & competing interests disclosure

Work in the authors’ laboratory was supported by Geron Corporation (Menlo Park, CA, USA), the Medical Research Council UK and the Oxford Stem Cell Institute at the James Martin 21st Century School (Oxford, UK). Further support to Ashleigh S Boyd was provided by NIH grant P20RR018757 and its administrative core. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.