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The novel method of osteocyte differentiation from human mesenchymal stem cells using gelatin sponge and its application to the treatment of rheumatoid

Research Project

Project/Area Number 18K16163
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

Miyagawa Ippei  産業医科大学, 大学病院, 助教 (10525463)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsヒト骨細胞 / ヒト間葉系幹細胞 / 関節リウマチ / バイオマテリアル / 骨細胞
Outline of Final Research Achievements

Human mesenchymal stem cells were cultured for 28 days in vitro in a three-dimensional environment using a gelatin hydrogel sponge as a scaffold. Based on the morphological evaluation by scanning electron microscope, we found that the cells accompanied by elongation of protrusions characteristic of osteocytes were induced. Furthermore, calcium phosphate deposition was confirmed by transmission electron microscopy and mass spectrometry. In addition, IL-1β stimulation and addition of PPARγ antagonists enhanced the expression of osteocyte markers, BSP, MEPE, SOST, and PHEX. Three-dimensional culture of human mesenchymal stem cells in vitro induces differentiation of human osteocyte, and it was effectively enhanced by the addition of IL-1β stimulation and inhibition of PPARγ.

Academic Significance and Societal Importance of the Research Achievements

近日、骨代謝における骨細胞の役割が注目されている。しかし、ヒト骨細胞は、生体内から単離することは困難で、さらに効率的な培養法が確立されていないため、骨細胞に関する研究はマウスを中心とした研究に留まり、ヒト骨細胞の役割に関して十分に検討されていない。本研究では、3次元環境下でヒト間葉系幹細胞を培養することでヒト骨細胞へ分化誘導されることを明らかにするとともにIL-1β刺激およびPPARγ阻害により効率化されることを明らかにした。本研究で確立された培養法を利用することで、骨粗鬆症や関節リウマチなど骨細胞が重要な役割を果たす多くの疾患の病態解明と新規治療法への展開を可能とする点で意義があると考える。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2021-02-19  

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