Functional parathyroid glands generated using blastocyst complementation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16337
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Kano Mayuko 聖マリアンナ医科大学, 医学部, 助教 (20868129)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 副甲状腺 / 多能性幹細胞

Outline of Final Research Achievements

We attempted to generate functional parathyroid glands (PTGs) from mouse embryonic stem cells (mESCs)by using blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. Using CRISPR-Cas9 knockout of Gcm2, we efficiently produced parathyroid deficient embryos for BC. In these embryos, mESCs differentiated into endocrinologically mature PTGs that rescued Gcm2 knockout mice from neonatal death. The mESC-derived PTGs responded well to extracellular calcium, restoring calcium homeostasis on transplantation into mice surgically rendered hypoparathyroid. These results demonstrate that BC can produce functional
endocrine organs and constitute a concept in treatment of hypoparathyroidism.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

受精卵ゲノム編集による効率的な臓器欠損胚の作製と胚盤胞補完法とを組み合わせることが、臓器補完の有用な手段となることが示唆された。Ca応答性のある機能的な副甲状腺を作製に成功したこと、多能性幹細胞由来の副甲状腺が移植臓器として有用であったことは、将来のヒト-動物間胚盤胞補完法によるヒト多能性幹細胞からの副甲状腺作製と臨床応用の可能性を示すものである。