Growing Thyroid Tissue in the Spleen to Restore Function
Over the past decade or so, researchers have demonstrated that it is possible to use existing organs as bioreactors to host organoids derived from other organ tissues. Functional liver tissue can be grown in lymph nodes, as can thymus tissue. Here, researchers show that thyroid organoids can be grown in the spleen. This is intended to help patients who have undergone thyroidectomy, but will this capability also be useful in the context of the aging of the thyroid gland? Interestingly, the aging of the thyroid is poorly understood in comparison to the interaction of aging with larger organs such as liver, kidney, or heart. The thyroid produces important hormones, and those levels change with age, but it is unclear as to whether this is a dysfunction or a compensatory response.
Patients undergoing total thyroidectomy typically require lifelong oral levothyroxine sodium (L-T4) treatment. While effective in maintaining basic serum hormone levels, this treatment falls short in restoring the dynamic responsive regulatory capacity of triiodothyronine (T3), essential for critical physiologic regulatory functions. Clinical data indicates that T3 deficiency can elevate the risk of hypertension, cardiac dysfunction, and other metabolic or mental health conditions.
Researchers have proposed an innovative solution to thyroid transplantation challenges by growing the thyroid in the spleen. Leveraging the spleen's unique properties, characterized by a loose structure and rich blood supply, the team explored a new strategy for thyroid regeneration. Intrasplenic thyroid transplantation was performed without compromising the structure and function of the spleen. Mice with total thyroidectomy were transplanted with thyroid glands in the spleen, featuring intact follicles and reconstructed vascular networks. This approach successfully recapitulated the angio-follicular unit (AFU), leading to the full restoration of hormone levels in mice.
Furthermore, studies have demonstrated that this method is more effective in responding to physiological signals than hormone replacement therapy. Moreover, long-term evaluation of the effects with that of hormone replacement therapy proved that the regenerated thyroid glands in the spleen completely restored the physiological homeostasis in the mice after total thyroidectomy without any negative side effects, indicating significant potential for clinical applications.
Enhanced mTORC1 signaling and protein synthesis in pathologic α-synuclein cellular and animal models of Parkinson's disease
https://www.science.org/doi/full/10.1126/scitranslmed.add0499
https://www.newswise.com/articles/new-findings-about-key-pathological-protein-in-parkinson-s-disease-open-paths-to-novel-therapies
Experiments in mice genetically manipulated to over-express the pathological form of alpha-synuclein showed that it indeed caused cells to increase protein synthesis by activating mTOR.
This process was triggered, the researchers say, when the pathological alpha-synuclein bound to another protein, tuberous sclerosis complex 2 (TSC2), preventing it from connecting with yet another protein TSC1, that keeps mTOR in check.
Treating the genetically engineered mice with rapamycin, a drug that targets mTOR, not only prevented excessive protein production in mice with a condition like Parkinson's disease, but also eased some of the slow, halting movements and weak grip strength that are hallmarks of Parkinson's disease in people.