Differentiation of parathyroid hormone expressing cells from human pluripotent stem cells

Abstract
Differentiation of pluripotent stem cells into functional parathyroid-like cells would accelerate development of important therapeutic options for subjects with parathyroid-related disorders, from the design and screening of novel pharmaceutical agents to the development of durable cellular therapies. We have established a highly reproducible directed differentiation approach leading to parathyroid hormone (PTH) expressing cells from human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC). We accomplished this through the comparison of multiple different basal media, the inclusion of the CDK inhibitor PD0332991 in both definitive endoderm (DE) and anterior foregut endoderm (AFE) stages, and a 2-stage pharyngeal endoderm (PE) series. This is the first protocol to reproducibly establish PTH expressing-cells from human pluripotent stem cells and represents a first step towards the development of functional parathyroid cells with broad applicability for medicinal and scientific investigation.