Influence of donor-recipient age differences in allogenic rat thyroid transplantation.

INTRODUCTION: Regenerative medicine for tissue dysplasia, hypoplasia, and functional impairment of tissues and cells has advanced considerably, and thyroid disease is no exception. Inducing differentiation of thyroid cells from patient-derived cells and transplanting them back into patients is an ideal approach because it eliminates the need for immunosuppressive drugs. However, the relationship between the maturity of cells or tissues derived from various sources and engraftment outcomes remains unclear. In this study, we evaluated the effect of donor-recipient age differences using thyroids from living rat donors, given the current lack of sufficiently mature stem cell-derived thyroid tissue. METHODS: Histological and gene expression differences were analyzed in thyroids of retired rats (>20 weeks old with impaired reproductive function) and 3-week-old rats. Thyroid transplantation experiments were conducted between age-matched or age-mismatched groups. Donor thyroids were implanted beneath the renal capsule of recipient rats without total thyroidectomy, and grafts from retired rats transplanted into 3-week-old rats were resected 1 and 6 months post-transplantation, while others were resected 1 month post-transplantation for immunohistological analysis and gene expression analysis of thyroid differentiation markers. RESULTS: Thyroids from 3-week-old rats and retired rats showed minimal histological and functional differences; however, the expression levels of several thyroid-specific marker genes were significantly higher in retired rats. When thyroids were transplanted between age-matched donors and recipients, clear engraftment was observed at 1 month. Although robust engraftment was also observed when thyroids from retired rats were transplanted into 3-week-old recipients at both 1 and 6 months, transplantation of thyroids from 3-week-old donors into retired rats resulted in disrupted follicular structures and fibrotic changes at 1 month. In contrast, mRNA expression levels of transplanted thyroids presented no significant differences between age-matched and age-mismatched transplantation. CONCLUSIONS: Mismatch between donor thyroid maturity and recipient age may influence engraftment in rat allogenic thyroid transplantation.