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

Palaniappan Sethu, Thomas A. Haglund, Aaron J. Rogers, Herbert Chen, John Porterfield, Courtney J. Balentine

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalCells Tissues Organs
Volume206
Issue number1-2
DOIs
StatePublished - May 1 2019
Externally publishedYes

Fingerprint

Hyperparathyroidism
Calcium-Sensing Receptors
Parathyroid Hormone
Calcium
Parathyroid Glands
Therapeutics
Cell Culture Techniques
Fluorescence
Staining and Labeling
Bone and Bones
Growth

Keywords

  • Engineered tissue
  • Organoid
  • Parathyroid
  • Pseudogland

ASJC Scopus subject areas

  • Anatomy
  • Histology

Cite this

Growing Human Parathyroids in a Microphysiological System : A Novel Approach to Understanding and Developing New Treatments for Hyperparathyroidism. / Sethu, Palaniappan; Haglund, Thomas A.; Rogers, Aaron J.; Chen, Herbert; Porterfield, John; Balentine, Courtney J.

In: Cells Tissues Organs, Vol. 206, No. 1-2, 01.05.2019, p. 54-61.

Research output: Contribution to journalArticle

Sethu, Palaniappan ; Haglund, Thomas A. ; Rogers, Aaron J. ; Chen, Herbert ; Porterfield, John ; Balentine, Courtney J. / Growing Human Parathyroids in a Microphysiological System : A Novel Approach to Understanding and Developing New Treatments for Hyperparathyroidism. In: Cells Tissues Organs. 2019 ; Vol. 206, No. 1-2. pp. 54-61.
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