Title:
PLURIPOTENT STEM CELL-DERIVED CEREBROVASCULAR ENDOTHELIAL CELLS AND PRODUCTION METHOD THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/074363
Kind Code:
A1
Abstract:
Provided are pluripotent stem cell-derived cerebrovascular endothelial cells capable of accurately reflecting the transport function of human BBB and a production method of the same. The cerebrovascular endothelial cells are obtained by introducing MDR1 gene encoding P-gp into pluripotent stem cells and then inducing the differentiation into the cerebrovascular endothelial cells. The pluripotent stem cell-derived cerebrovascular endothelial cells of the present invention express P-gp at a high level, have a high barrier function, and retain an excellent function as a drug efflux transporter. The pluripotent stem cell-derived cerebrovascular endothelial cells of the present invention have an excellent drug efflux transporter function that has never been achieved by immortalized cerebrovascular endothelial cell lines established from human cerebrovascular endothelial cells. Moreover, the pluripotent stem cell-derived cerebrovascular endothelial cells of the present invention accurately reflect the transport function of human BBB and thus make it possible to overcome the problem of the difficulty of obtaining cerebrovascular endothelial cells having comparable properties occurring in primary cerebrovascular endothelial cells.
Inventors:
KAWABATA KENJI (JP)
YAMAGUTI TOMOKO (JP)
DEGUCHI YOSHIHARU (JP)
YAMAGUTI TOMOKO (JP)
DEGUCHI YOSHIHARU (JP)
Application Number:
PCT/JP2022/037993
Publication Date:
May 04, 2023
Filing Date:
October 12, 2022
Export Citation:
Assignee:
NAT INST BIOMEDICAL INNOVATION HEALTH & NUTRITION (JP)
UNIV TEIKYO (JP)
UNIV TEIKYO (JP)
International Classes:
C12N5/10; C12N5/071; C12N15/12; C12Q1/02
Foreign References:
| JP2015159785A | 2015-09-07 | |||
| US20190048316A1 | 2019-02-14 |
Other References:
TOMOKO YAMAGUCHI, BIMAO JIANG NISHIJIMA, HONGYAN ZHANG, YOSHIHARU DEGUCHI, KENJI KAWABATA: "28Q-pm089 Development of blood-brain barrier model using MDR1-overexpressed iPS cells", 140TH ANNUAL MEETING OF THE PHARMACEUTICAL SOCIETY OF JAPAN; KYOTO, JAPAN; MARCH 25-28, 2020, vol. 140, 1 January 2020 (2020-01-01) - 28 March 2020 (2020-03-28), XP009546683
SAKO, DAIKI ET AL.: "28C-pm05S Evaluation of transporter function in P-gp expressing human iPS cell-derived brain microvascular endothelial cells", 142ND ANNUAL MEETING OF THE PHARMACEUTICAL SOCIETY OF JAPAN; NAGOYA, JAPAN [VIRTUAL MEETING]; MARCH 25-28, 2022, vol. 142, 4 March 2022 (2022-03-04) - 28 March 2022 (2022-03-28), XP009546684
SAKO, DAIKI ET AL.: "28C-pm05S Evaluation of transporter function in P-gp expressing human iPS cell-derived brain microvascular endothelial cells", 142ND ANNUAL MEETING OF THE PHARMACEUTICAL SOCIETY OF JAPAN; NAGOYA, JAPAN [VIRTUAL MEETING]; MARCH 25-28, 2022, vol. 142, 4 March 2022 (2022-03-04) - 28 March 2022 (2022-03-28), XP009546684
Attorney, Agent or Firm:
SHOJI, Takashi et al. (JP)
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