Development of cross-species chimeric mouse production method using transplacental cell transplantation method and tissue stem cell deficient mouse.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21513
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Takahashi Satoru 筑波大学, 医学医療系, 教授 (50271896)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: キメラマウス / ヒト化マウス / 経胎盤 / 遺伝子改変マウス / 再生医療

Outline of Final Research Achievements

Using Tie-2-Cre;Runx1cKO as hematopoietic-deficient mice, we have successfully generated mice in which the hematopoietic system was replaced by that of rats, and mice with only the hematopoietic system of rats were successfully sustained for a long time. From these results, we think that we were able to demonstrate that mice with only the hematopoietic lineage of a heterologous animal can be generated by this method. We also demonstrated that human hematopoietic cells are maintained in adult mice even when human hematopoietic stem cells are transplanted into wild-type mice.
We also attempted to generate human pancreas using Pdx1-deficient mice which lack pancreas and Human pancreatic progenitor cells. We demonstrated that Pdx1-deficient mice can survive up to 8 days of age and that mRNA for human insulin can be detected in these mice.

Free Research Field

発生工学

Academic Significance and Societal Importance of the Research Achievements

動物を用いたヒト臓器の開発は、胚盤胞補完法を用いて研究が進んでいるが、倫理的な問題があること、ヒト幹細胞を用いた場合は、ヒト幹細胞が急速に排除されるなどの問題点が挙げられている。我々が開発した経胎盤細胞移植法はこれらの問題点を克服できる方法として学術的に重要であるとともに、動物を用いたヒト臓器の新たな作製方法として社会的意義が大きいと考えられる。