Thymus regeneration therapies
The thymus is central to T cell immunity and tolerance but lacks regenerative capacity, leaving patients with primary and secondary thymic impairments vulnerable to immunodeficiency, autoimmunity, and cancer.
Allogeneic thymus transplantation using cultured postnatal thymic tissue provides proof of concept for thymus function replacement therapies but is restricted to a small subset of patients with congenital athymia due to HLA mismatch and logistical challenges.
Advances in single-cell biology and stem cell engineering are converging to enable stem cell-based therapies, particularly induced pluripotent stem cell-derived thymic epithelial cells.
Induced pluripotent stem cell-derived thymic epithelial cells have the potential to reconstitute endogenous T cell development, tolerance, and immune surveillance across diverse clinical settings.
Thymic regeneration could not only transform rare immune disorders but also address aging-related immunosenescence and chronic diseases.
To treat patients with thymic injury and compromised but persistent residual T cell development and function, an HLA mismatch between induced pluripotent stem cell-derived thymic epithelial cells and the recipient has to be avoided to prevent rejection of the induced pluripotent stem cell-derived thymic epithelial cell graft. To reconcile the desire for a scalable, cost-effective, off-the-shelf approach with the need to avoid HLA mismatch in patients with residual T cell function, the generation of HLA-haploidentical induced pluripotent stem cell banks should be considered.
https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(26)00062-6
