Intrasplenic Thymus Organogenesis From Injectable Tissue Fragments Restores Functional T-cell immunity

Restoring thymic function is therefore critical for affected patients. Here, we describe intrasplenic thymus regeneration (ISTR), an approach in which cultured thymic tissue fragments are implanted into the spleens of athymic nude and humanized mice.

The spleen’s abundant vasculature and supportive stromal milieu enable rapid thymic organogenesis, leading to reconstitution of peripheral T-cell compartments with normal phenotypes and functional competence. Relative to intramuscular implantation, ISTR drives faster and more complete thymic development, generates greater T-cell output, and is associated with a lower incidence of graft-versus-host disease. Functional readouts show restored T-cell immunity, including protective responses to viral challenge and tumor models.