Thymic Involution: A Barrier or Opportunity for Cell Replacement Therapy?
Although regenerative medicine offers prospects for cell replacement therapies relevant to many disease states, research has mainly focused on regenerating major organ systems such as the heart, kidney and lungs. The thymus, however, undergoes natural age-related involution and its ability to sustain a functional T cell repertoire therefore declines throughout life. While in healthy adults this process has no significant immunological impact, in immunocompromised patients, the involuted thymus is unable to rescue immune homeostasis which leads to increased risk of infection. Regenerating the thymus using stem cell technology, may, therefore, provide a viable option for rescuing immune function in immune compromised or elderly patients. Furthermore, thymic regeneration offers the prospect of influencing the acceptance of allogeneic tissues through the induction of central tolerance. Here, we explore the rationale behind thymic transplantation and current efforts in the stem cell field aiming to derive functional thymic tissue.
KeywordsCell Repertoire DiGeorge Syndrome Mixed Chimerism Pharyngeal Pouch EpCAM1 Expression
We are indebted to Kate Silk, Naoki Ichiryu, Alison Leishman, Tim Davies and Patty Sachamitr for helpful discussions. SH holds an MRC Capacity Building Studentship awarded to the Oxford Stem Cell Institute. Work on thymic involution in the authors' laboratory was supported by Pfizer Regenerative Medicine.
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