Development of transvenous liver-specific mesenchymal stem cell transplantation therapy by cell-modification

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H02100
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Osaka University
• Principal Investigator: Yamashita Shizuya 大阪大学, 産業科学研究所, 招へい教授 (60243242)
• Co-Investigator(Kenkyū-buntansha): 小関 正博 大阪大学, 医学系研究科, 助教 (10467582) ; 黒田 俊一 大阪大学, 産業科学研究所, 教授 (60263406)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 幹細胞移植 / 家族性高コレステロール血症 / 細胞治療 / 糖鎖修飾

Outline of Final Research Achievements

Aiming at the development of mesenchymal stem cell transplantation therapy for patients with homozygous familial hypercholesterolemia (FH), we have developed a technology to modify stem cell surface with glycosylated-fatty acid, which has a specific receptor in the liver, to enable liver-specific cell transplantation even after transvenous cell transplantation. Although the cells were modified with glycolipid derivatives of fatty acids bound to sugar chain X, labeled with fluorescent dyes, and studied by tail vein injection into nude mice for in vivo imaging, it has been difficult to solve the issue of cytotoxicity.
On the other hand, we created a genetic diagnosis panel for dyslipidemia in more than 100 patients with FH and performed genetic analysis, and obtained findings such as the presence of double gene mutations that may be useful for transplantation.

Free Research Field

脂質代謝

Academic Significance and Societal Importance of the Research Achievements

幹細胞自体に修飾を行うことによって、臓器特異的に移植細胞を送達しようとする試みは独創的であった。しかしながら細胞修飾による細胞毒性の克服には課題があった。
家族性高コレステロール血症患者に対しては、世界的には完全ヒト化モノクローナル抗体医薬の開発が進んでいるが、あくまで根治的な治療は肝臓におけるLDL受容体活性を回復することである。被験者になりうる患者の遺伝子変異情報を得られたことは、最終的な細胞移植療法の実現につながると考えられる。