Thymus fragments implanted in the spleen restored T-cell immunity in mice and in a humanized model
Thymus fragments implanted in the spleen restored the source of immune T-cells in mice
Researchers compared two sites for transplanting cultured thymus fragments: the spleen and muscle. Identical fragments formed thymic tissue more quickly and produced more new T-cells in the spleen. In a humanized mouse model containing human tissues, the fragments also generated more human T-cells in the spleen.
The thymus is the organ where T-cells mature. These immune cells recognize infections and tumor cells while learning to avoid attacking the body’s own tissues. The thymus shrinks with age and produces fewer new T-cells. In an article published on August 25, researchers tested whether transplanted thymic tissue could restore this function when grown inside another organ.
The choice of the spleen followed from earlier work by the same research group. In 2023, some members of the team grew thyroid fragments in the spleens of mice. The fragments formed follicles and restored hormone production after the animals’ own thyroid glands were removed. In the current study, the researchers applied the same approach to the thymus, an organ that continually replenishes the immune cell pool.
The thymus fragments were cultured for at least six days. During this period, donor T-cells left the fragments while the structural basis of the future tissue remained intact. The researchers then transplanted identical fragments into mice whose own thymus had been removed. One group received the fragments in the spleen, while the other received them in muscle. This design allowed the researchers to compare how the transplantation site affected the same tissue.
After two weeks, the fragment in the spleen had already formed cortical and medullary regions, where T-cells pass through successive stages of maturation. By the eighth week, its mass had reached approximately half the mass of the thymus in a healthy control mouse. Fragments in muscle remained below one tenth of that mass. The researchers found signs in the blood that T-cells had recently emerged from the new thymus. These cells also had a broad repertoire of receptors used to recognize targets.
The researchers then infected the mice with two viruses. Animals with a thymus fragment in the spleen had lower viral loads and less organ damage. In tumor experiments, their T-cells responded more actively, with responses approaching those of animals that retained their own thymus. Splenic fragments also grew better than intramuscular fragments in 20-month-old mice. In humanized mice, cryopreserved fragments of human thymus transplanted together with human hematopoietic stem cells produced more human T-cells in the spleen than in muscle.
In this comparison, the transplantation site determined the outcome of otherwise identical fragments. The fragments formed a functional thymus more successfully in the spleen than in muscle.