Mírian Romitti

Thyroid hormones play a pivotal role in diverse physiological processes, and insufficient synthesis of these hormones results in hypothyroidism, a prevalent disorder with a significant global impact. Research has shown that the residual thyroid tissue following surgery fails to fully regenerate the gland and restore normal function. The slow turnover rate of the thyroid gland and the presence of resident stem cells, which may contribute to regeneration within adult thyroid tissue, are topics of ongoing debate. This comprehensive review summarizes current research findings concerning the regeneration of the adult thyroid. Investigations have identified potential cellular mechanisms implicated in thyroid regeneration following partial tissue damage, including cells within microfollicles and a cluster of potential thyroid progenitors cells. Nevertheless, the exact mechanisms remain elusive. In cases of complete removal of the thyroid gland, regeneration does not occur, underscoring the necessity for an external source of thyroid tissue. The transplantation of thyroid organoids has emerged as a promising approach to restore thyroid function. Researchers have successfully derived thyroid organoids from various sources and demonstrated their functionality in both in vitro and in vivo animal models. Despite the challenges that still need to be addressed in achieving full maturation and functionality of human thyroid organoids, significant strides have been made in this regard. This review explores the potential of thyroid organoid transplantation and its implications for the field of regenerative medicine.

Pulmonary arterial hypertension (PAH) is a rare and severe disorder characterized by progressive pulmonary vasculopathy. Growth differentiation factor ( GDF ) 2 encodes the pro‐protein bone morphogenetic protein (BMP) 9, activated after cleavage by endoproteases into an active mature form. BMP9, together with BMP10, are high‐affinity ligands of activin receptor‐like kinase 1 (ALK1) and BMP receptor type II (BMPR2). GDF2 mutations have been reported in idiopathic PAH with most patients being heterozygous carriers although rare homozygous cases have been described. The link between PAH occurrence and BMP9 or 10 expression level is still unclear. In this study, we describe a pediatric case of PAH also presenting with telangiectasias and epistaxis. The patient carries the novel homozygous GDF2 c.946A > G mutation, replacing the first arginine of BMP9's cleavage site (R316) by a glycine. We show that this mutation leads to an absence of circulating mature BMP9 and mature BMP9‐10 heterodimers in the patient's plasma although pro‐BMP9 is still detected at a similar level as controls. In vitro functional studies further demonstrated that the mutation R316G hampers the correct processing of BMP9, leading to the secretion of inactive pro‐BMP9. The heterozygous carriers of the variant were asymptomatic, similarly to previous reports, reinforcing the hypothesis of modifiers preventing/driving PAH development in heterozygous carriers.