Growing Human Parathyroids in a Microphysiological System: A Novel Approach to Understanding and Developing New Treatments for Hyperparathyroidism

Abstract

We developed a novel model for studying hyperparathyroidism by growing ex vivo 3-dimensional human parathyroids as part of a microphysiological system (MPS) that mimics human physiology. The purpose of this study was to validate the parathyroid portion of the MPS. We prospectively collected parathyroid tissue from 46 patients with hyperparathyroidism for growth into pseudoglands. We evaluated pseudogland architecture and calcium responsiveness. Following 2 weeks in culture, dispersed cells successfully coalesced into pseudoglands ∼500–700 µm in diameter that mimicked the appearance of normal parathyroid glands. Functionally, they also appeared similar to intact parathyroids in terms of organization and calcium-sensing receptor expression. Immunohistochemical staining for calcium-sensing receptor revealed 240–450/cell units of mean fluorescence intensity within the pseudoglands. Finally, the pseudoglands showed varying levels of calcium responsiveness, indicated by changes in parathyroid hormone (PTH) levels. In summary, we successfully piloted the development of a novel MPS for studying the effects of hyperparathyroidism on human organ systems. We are currently evaluating the effect of PTH on adverse remodeling of tissue engineered cardiac, skeletal, and bone tissue within the MPS.

Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration

“…Another key point of this study is that it used normal human-derived cells. Cell lines, 1,2,51,52 patient-derived parathyroid cells, 34,53 and animal-derived cells 54 have been used in parathyroid research, but these approaches may have limitations in representing human normal parathyroid cells. As shown in Fig.…”

Organ‐on‐a‐chip technologies for biomedical research and drug development: A focus on the vasculature

“…In research, both in silico 89 and OOC models 90 are ideally integrated to predict complex hormone dynamics. However, OOC technologies of the endocrine system are poorly represented 59 and limited to the parathyroid glands, 91 pancreas, 92,93 and neuroendocrine research. 94…”