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Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. 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