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Related Concept Videos

The Parathyroid Glands00:59

The Parathyroid Glands

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The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by...
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Related Experiment Video

Updated: Jul 25, 2025

Two-step Approach to Explore Early- and Late-stages of Organ Formation in the Avian Model: The Thymus and Parathyroid Glands Organogenesis Paradigm
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Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation.

Mayuko Kano1,2,3, Naoaki Mizuno1,2, Hideyuki Sato1,2

  • 1Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8510, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|June 28, 2023
PubMed
Summary
This summary is machine-generated.

Blastocyst complementation successfully generated functional parathyroid glands from mouse stem cells. This approach offers a promising new strategy for treating hypoparathyroidism and restoring calcium homeostasis.

Keywords:
aparathyroid mouseblastocyst complementationembryonic stem cellshypoparathyroidparathyroid glands

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Area of Science:

  • Endocrinology
  • Developmental Biology
  • Regenerative Medicine

Background:

  • Permanent hypoparathyroidism necessitates lifelong therapy with limited efficacy.
  • Current in vitro stem cell-derived parathyroid cells lack essential calcium-sensing functions.
  • Functional parathyroid gland transplantation is a potential alternative for improved patient outcomes.

Purpose of the Study:

  • To investigate blastocyst complementation (BC) as a strategy for generating functional parathyroid glands (PTGs).
  • To assess the potential of BC-derived PTGs for restoring calcium homeostasis in hypoparathyroid models.
  • To explore the feasibility of interspecies PTG generation for future human therapeutic applications.

Main Methods:

  • Generation of aparathyroid mouse embryos using CRISPR-Cas9 knockout of *Glial cells missing2* (*Gcm2*).
  • Blastocyst complementation using mouse embryonic stem cells (mESCs) to generate PTGs.
  • Transplantation of mESC-derived PTGs into *Gcm2* knockout mice and surgically hypoparathyroid mice.
  • Interspecies blastocyst complementation in *Gcm2* knockout rat neonates.

Main Results:

  • Fully functional PTGs were generated from mESCs via single-step BC.
  • mESC-derived PTGs differentiated, matured, and rescued *Gcm2* knockout mice from neonatal death.
  • Transplanted mESC-derived PTGs responded to extracellular calcium and restored calcium homeostasis.
  • Functional interspecies PTGs were successfully generated in rat neonates.

Conclusions:

  • Blastocyst complementation is a viable method for producing functional endocrine organs, specifically PTGs.
  • This approach offers a novel concept for the treatment of permanent hypoparathyroidism.
  • Interspecies BC holds potential for developing xenogeneic animal models for future human parathyroid therapy.