Title:
ISLET-LIKE ORGANOID EXPRESSING MONSTIM1 IN WHICH INSULIN SECRETION IS REGULATED BY OPTICAL STIMULATION
Document Type and Number:
WIPO Patent Application WO/2023/101369
Kind Code:
A1
Abstract:
The present invention relates to an islet-like organoid in which insulin secretion can be optically regulated by differentiating, into pancreatic islets, human pluripotent stem cells (monSTIM1-hPSC) obtained by knocking-in monSTIM1, which is an inducer of Ca2+ concentration increase (Ca2+ transient), into the AAVS1 locus of the stem cells. Since it has been confirmed in vitro and in the body of a diabetic mouse model that the islet-like organoid of the present invention can secrete insulin through an intracellular calcium influx increased by light irradiation, the islet-like organoid can be effectively used in the treatment of diabetic patients.
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Inventors:
HAN YONG MAHN (KR)
HEO WONDO (KR)
CHOI JI EUN (KR)
LEE JINSU (KR)
SHIN EUN JI (KR)
HEO WONDO (KR)
CHOI JI EUN (KR)
LEE JINSU (KR)
SHIN EUN JI (KR)
Application Number:
PCT/KR2022/019109
Publication Date:
June 08, 2023
Filing Date:
November 29, 2022
Export Citation:
Assignee:
KOREA ADVANCED INST SCI & TECH (KR)
International Classes:
C12N5/071; A61F2/02; A61L27/38; A61P3/10; C12N13/00
Foreign References:
| KR20200055677A | 2020-05-21 | |||
| KR20150067945A | 2015-06-19 |
Other References:
YOUNGJIN KIM, HYEONGSEOK KIM, UNG HYUN KO, YOUJIN OH, AJIN LIM, JONG-WOO SOHN, JENNIFER H. SHIN, HAIL KIM, YONG-MAHN HAN: "Islet-like organoids derived from human pluripotent stem cells efficiently function in the glucose responsiveness in vitro and in vivo", SCIENTIFIC REPORTS, vol. 6, no. 1, 1 December 2016 (2016-12-01), XP055748631, DOI: 10.1038/srep35145
KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY: "Development of disease modeling and differentiation platform technology using human disease-specific induced pluripotent stem cells", STEM CELL RESEARCH PROJECT FINAL REPORT, 29 July 2020 (2020-07-29), pages 1 - 134, XP009546996
KONO TATSUYOSHI, TONG XIN, TALEB SOLAEMA, BONE ROBERT N., IIDA HITOSHI, LEE CHIH-CHUN, SOHN PAUL, GILON PATRICK, ROE MICHAEL W., E: "Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell", DIABETES, AMERICAN DIABETES ASSOCIATION, US, vol. 67, no. 11, 1 November 2018 (2018-11-01), US , pages 2293 - 2304, XP093070580, ISSN: 0012-1797, DOI: 10.2337/db17-1351
ZHANG FAN, TZANAKAKIS EMMANUEL S.: "Optogenetic regulation of insulin secretion in pancreatic β-cells", SCIENTIFIC REPORTS, vol. 7, no. 1, XP093070603, DOI: 10.1038/s41598-017-09937-0
KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY: "Development of disease modeling and differentiation platform technology using human disease-specific induced pluripotent stem cells", STEM CELL RESEARCH PROJECT FINAL REPORT, 29 July 2020 (2020-07-29), pages 1 - 134, XP009546996
KONO TATSUYOSHI, TONG XIN, TALEB SOLAEMA, BONE ROBERT N., IIDA HITOSHI, LEE CHIH-CHUN, SOHN PAUL, GILON PATRICK, ROE MICHAEL W., E: "Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell", DIABETES, AMERICAN DIABETES ASSOCIATION, US, vol. 67, no. 11, 1 November 2018 (2018-11-01), US , pages 2293 - 2304, XP093070580, ISSN: 0012-1797, DOI: 10.2337/db17-1351
ZHANG FAN, TZANAKAKIS EMMANUEL S.: "Optogenetic regulation of insulin secretion in pancreatic β-cells", SCIENTIFIC REPORTS, vol. 7, no. 1, XP093070603, DOI: 10.1038/s41598-017-09937-0
Attorney, Agent or Firm:
LEE, Won Hee (KR)
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