Strategies for thymic regeneration: Recent advances towards clinical therapy

The thymus plays a critical role in maintaining immune well-being, but paradoxically undergoes progressive age-related atrophy. Many efforts have been made to deepen our understanding of its biology, with future therapies aimed at re-establishing T cell production in immunocompromised patients. This includes the elderly, and patients undergoing cytoablative treatments or chronically infected with immunotropic viruses. Here we discuss major pre-clinical approaches to thymic regeneration, as a representation of the strategies potentially able to be utilised therapeutically. We outline thymic physiology and development to assist in understanding the rationale behind each regenerative strategy - broadly, reactivation of endogenous thymic epithelial progenitor cells, de novo generation of thymic epithelium, and the facilitating effects on these of bioengineering. Continued advancement in these approaches may lead to their clinical translation for the recovery of immune competence in the aged or immune deficient, and tolerance applications in the developing field of stem cell therapeutics.