Report of UZH-KU Joint Research Project
Section 1
Project title:

Towards a universal solution: Editing iPSCs for stroke therapy

Project coordinator (KU)
Name
Position
Faculty, department
Project coordinator (UZH)
Name
Position
Faculty, department

Prof. Dr. Akitsu Hotta
Associate Professor
Center for iPS Cell Research and Application (CiRA), Kyoto University

Period of project
Project location

Dr. Christian Tackenberg
Group Leader and Scientific Head of Stem Cell ResearchInstitute for Regenerative Medicine (IREM), University of Zurich
From: 1.9.2021
To: ongoing
Institute for Regenerative Medicine, University of Zurich[KU] Faculty members:

No. of participantsStudents:

Others:[UZH] Faculty members: Dr. Ruslan Rust, Institute for Regenerative
Medicine, UZH;
Students:
Others:*A participant list can be attached instead of completing the above section. The list should
include the details above.

URL at which project
outcomes can be viewed (e.g.
workshop
notifications/programs/reports,evidence of academic papers
published or otherwise madeavailable, etc.)
Photographs with captions

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used in your report as attachments. The size of each image should be 4MB,
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Section 2
Summary of the project (approx. 200 words)*KU project leaders are required to submit a summary of the project in Japanese in addition to theEnglish summary (approx. 400 characters).
Stem cell therapy has huge potential for brain regeneration after stroke. Autologous approaches arelimited due to timely production, logistics, and high costs. Allogeneic cells on the other hand require
immune suppression to protect the graft from immune rejection. Thus, the use of highly immunecompatible, so-called hypoimmunogenic or „universal“ cells, represents a highly promising approach.
In the proposed project, we aim to develop and preclinically validate universal iPSCs for cell therapy instroke. This will be accomplished through a close collaboration between Dr. Ruslan Rust and Dr.
Christian Tackenberg (IREM, University of Zurich), who are working on cell-based therapies following
stroke, and Dr. Akitsu Hotta (CiRA, Kyoto University), who specializes in the generation of allogeneic,
universal iPS cell lines.
As a first step, the legal framework for the cooperation has been created. Universal iPS cell lines havebeen transferred from CiRA to IREM and have been successfully adapted and expanded in cell culture.
The obtained cells have been differentiated into neural progenitor cells (NPCs) which will betransplanted into stroked mice with a humanized immune system to determine the regenerative
potential of universal NPCs following stroke.

幹細胞治療は、脳卒中後の脳再生に大きな可能性がある。しかし、自家細胞移植は、製造時間、調達、および高コスト等が課題となっている。一方、同種(他家)細胞は、移植片を免疫拒絶反応から守るために免疫抑制が必要である。したがって、免疫適合性の高い「低抗原性細胞」を用いることは、非常に魅力的なアプローチである。
このプロジェクトでは、脳卒中の細胞治療のための低抗原性 iPSC を開発し、前臨床試験で検証することを目的としている。これは、脳卒中後の細胞治療に取り組んでいる Ruslan Rust 博
士と Christian Tackenberg 博士、および低抗原性 iPS 細胞株を作製した堀田との密接な協力により進められる。
共同研究の第一段階として、契約の枠組みを整えた。低抗原性 iPS 細胞株を CiRA から IREMに提供し、細胞培養の適応および神経前駆細胞(NPC)への分化誘導に成功した。今後は脳卒中モデルのヒト化免疫マウスに移植し、再生能力を調べる予定である。

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