Strategies for Thymic Regeneration: Recent Advances Towards Clinical Therapy

  • Marco Barsanti
  • Michael Hun
  • Richard Boyd
  • Ann Chidgey


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.


Hematopoietic Stem Cell Transplantation Keratinocyte Growth Factor Thymic Epithelial Cell Double Positive Thymic Involution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Allogeneic HSCT


Anterior definitive endoderm


Autoimmune regulator


B cell lymphoma 2


Biomimetic materials


Bone marrow


Bone marrow transplantation


Bone morphogenetic protein 4


Chemokine (C-C motif) ligand 21


Chemokine (C-C motif) receptor 7


Chemokine (C-X-C motif) ligand 12


Common lymphoid progenitor




Cortico-medullary junction


Cortico-medullary junction




Delta-like ligands


Dendritic cell


DiGeorge syndrome chromosomal region 8


Double positive


Embryonic day


Embryonic stem cells


Experimental autoimmune encephalomyelitis


Extracellular matrix


Fgf receptor 2 variant IIIb


Fibroblast growth factor 8


Forkhead box-containing gene n1


Forkhead-box gene a2


G protein-coupled receptors




Glial cell missing homologue 2


Graft versus host disease


Growth hormone


Growth hormone releasing hormone


Hematopoietic stem cell transplantation




Human immunodeficiency virus


Hypoxia inducible factor-1 alpha


Induced pluripotent stem cells


Induced TECs


Insulin-like growth factor 1


Interferon alpha






Keratinocyte growth factor




Kruppel-like factor 4


Label retaining cells


Luteinising hormone releasing hormone


Lymphoid tissue inducer


Major histocompatibility complex




Mesendoderm to anterior definitive endoderm to pharyngeal endoderm




Mouse embryonic fibroblasts


Mouse thymic stroma 24


mTECs characterised by high MHCII expression


mTECs characterised by low MHCII expression


Musculoaponeurotic fibrosarcoma oncogene homologue B


Myelin oligodendrocyte glycoprotein


Neural crest


Oct4 Klf4, Sox2 and c-Myc


Octamer-binding transcription factor 4


Paired box gene


Pax-Eyes absent homologue


Placenta-expressed transcript-1


Platelet (P)-selectin glycoprotein ligand 1


Platelet-derived growth factor receptor alpha


Polyethylene glycol


Reactive oxygen species


Retinoic acid


RNA interference


Sex determining region Y-box 2


Sex steroid ablation


Sine oculis-related homeobox homologue


Single positive


Smooth muscle cell


Sodium dodecyl sulfate




Sonic hedgehog




Stem cell factor


Sub-lethal total body irradiation


T box gene


T cell receptors


T regulatory


Third pharyngeal pouch




Thymic epithelial cells


Thymic epithelial progenitor cell


Thymic stromal cells


Tissue-restricted self-antigens


Transforming growth factor-β


Transit amplifying


Triple negative


Tumour necrosis factor


Tumour protein 63


Ulex europaeus agglutinin-1


Vascular-endothelial growth factor


v-myc avian myelocytomatosis viral oncogene homolog




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Copyright information

© Springer Japan 2016

Authors and Affiliations

  • Marco Barsanti
    • 1
  • Michael Hun
    • 1
  • Richard Boyd
    • 1
  • Ann Chidgey
    • 1
  1. 1.Department of Anatomy and Developmental BiologyMonash UniversityMelbourneAustralia

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