Development of vascular endothelium reconstitution method in vivo for organ transplantation.

• Project/Area Number: 17K10536
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Hamanaka Sanae 東京大学, 医科学研究所, 特任研究員 (40511415)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血管内皮 / 再構築 / 多能性幹細胞 / 胚盤胞補完法

Outline of Final Research Achievements

To generate pluripotent stem cells (PSCs)-derived vascular endothelial cells in vivo, we performed blastocyst complementation with injecting PSCs into Flk-1 deficient mouse blastocyst. This Flk-1 deficient is embryonic lethal due to an early defect in endothelial and hematopoietic cells.
In this study, we successfully generated vascular endothelial cells and blood derived from mouse PSCs (ES/iPS cells) in Flk-1 deficient chimeric mice by blastocyst complementation. And the Flk-1 deficient chimeric mice survived to adulthood without any abnormality.
Based on the above, this study achieved "Development of vascular endothelium reconstitution method in organ ".

Academic Significance and Societal Importance of the Research Achievements

拒絶反応を起こさない移植可能な臓器の作製には、臓器のみならず臓器内の血管内皮細胞も同時に多能性幹細胞から作製する必要がある。これまで本研究グループは動物体内で多能性幹細胞由来の臓器作製に取り組んできたが、今回の成果を組み合わせることで、目的の臓器だけでなく臓器内の血管内皮と血液細胞も同時に多能性幹細胞から作製可能であることが予想される。本研究成果は、動物体内での拒絶反応を起こしにくい移植用臓器の作製法として再生医療に大きく貢献するものと期待される。

Research Products

• [Journal Article] Compensation of Disabled Organogeneses in Genetically Modified Pig Fetuses by Blastocyst Complementation. (2020)
  • Author(s): Matsunari H, Watanabe M, Hasegawa K, Uchikura A, Nakano K, Umeyama K, Masaki H, Hamanaka H, Yamaguchi T, Nagaya M, Nishinakamura R, Nakauchi H, Nagashima H.
  • Journal Title: Stem Cell Reports. Volume: 14(1) Issue: 1 Pages: 21-33
  • DOI: 10.1016/j.stemcr.2019.11.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An interspecies barrier to tetraploid complementation and chimera formation (2018)
  • Author(s): Yamaguchi Tomoyuki、Sato Hideyuki、Kobayashi Toshihiro、Kato-itoh Megumi、Goto Teppei、Hara Hiromasa、Mizuno Naoaki、Yanagida Ayaka、Umino Ayumi、Hamanaka Sanae、Suchy Fabian、Masaki Hideki、Ota Yasunori、Hirabayashi Masumi、Nakauchi Hiromitsu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 15289-15298
  • DOI: 10.1038/s41598-018-33690-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation. (2018)
  • Author(s): Hamanaka S, Umino A, Sato H, Hayama T, Yanagida A, Mizuno N, Kobayashi T, Kasai M, Suchy FP, Yamazaki S, Masaki H, Yamaguchi T, Nakauchi H.
  • Journal Title: Stem Cell Reports. Volume: 11(4) Issue: 4 Pages: 988-997
  • DOI: 10.1016/j.stemcr.2018.08.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 胚盤胞補完法による多能性幹細胞由来の血管内皮細胞および造血細胞の同時作製 (2018)
  • Author(s): 濱仲早苗
  • Organizer: 第17回日本再生医療学会総
• [Presentation] 胚盤胞補完法による多能性幹細胞由来の血管内皮細胞および造血細胞の同時作製 (2017)
  • Author(s): 濱仲早苗
  • Organizer: 生命科学系学会合同年次大会 第40回日本分子生物学会