Umbilical cord mesenchymal stem cell-derived exosomes ameliorate parathyroid ischemic injury via inhibition of the neutrophil cytosolic factor 4-nuclear factor kappa B pathway

BACKGROUNDPost-surgical hypoparathyroidism results primarily from mechanical injury to parathyroid tissue or vascular injury during thyroid surgery, leading to glandular ischemia and dysfunction.Patients characteristically exhibit severe hypocalcemia and significantly reduced parathyroid hormone (PTH) secretion.The conventional management strategy involves prolonged high-dose supplementation with calcium and active vitamin D. While this approach partially ameliorates hypocalcemia, it cannot substitute for the physiological actions of PTH, especially PTH-mediated calcium reabsorption in the kidney.Therefore, chronic high-dose calcium therapy commonly results in hypercalciuria, substantially elevating the risk of renal dysfunction, kidney stones, and ectopic calcification.Restoration of parathyroid function following surgical injury represents a critical clinical challenge. AIMTo investigate the effect of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) on rabbit parathyroid injury and to elucidate the mechanism. METHODSWe established a rabbit parathyroid ischemia model by ligating the superior thyroid artery branches supplying both parathyroid glands.UCMSC-Exo was injected into the capsule of the parathyroid gland to evaluate the levels of serum PTH and calcium, the histological changes of the parathyroid gland, cell apoptosis and proliferation.Additionally, we studied the effect of UCMSC-Exo on hypoxia-induced damage to rabbit parathyroid cells.Subsequently, rabbit parathyroid tissues were analyzed to elucidate the mechanism by which UCMSC-Exo improves parathyroid injury.4 / 33 RESULTSThe results showed that UCMSC-Exo treatment significantly restored PTH and serum calcium levels, alleviated the histological damage of the parathyroid gland, inhibited mitochondrial dysfunction, inhibited cell apoptosis, and promoted cell proliferation.Moreover, in vitro experiments demonstrated that UCMSC-Exo could inhibit the generation of reactive oxygen species in hypoxia-induced parathyroid cells, inhibit cell apoptosis, and promote cell proliferation.Through sequencing and western blot, we found that UCMSC-Exo exerted its protective effect by inhibiting the neutrophil cytosolic factor 4-nuclear factor kappa B signaling pathway. CONCLUSIONThese findings indicate that local subcapsular injection of UCMSC-Exo has beneficial effects on improving rabbit parathyroid injury and is a promising therapeutic strategy for preventing parathyroid dysfunction after thyroid surgery.