In vivo generation of hematopoietic stem cells from human iPS cells in sheep fetal liver

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21315
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology; Integrative animal science
• Research Institution: Jichi Medical University
• Principal Investigator: Abe Tomoyuki 自治医科大学, 医学部, 講師 (20610364)
• Research Collaborator: HANAZONO Yutaka 自治医科大学, 医学部, 教授 (70251246) ; NAGAO Yoshikazu 宇都宮大学, 農学部, 教授 (70291953)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 造血幹細胞 / ニッチ / 多能性幹細胞 / 大型動物 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Generating hematopoietic stem cells (HSCs) from human iPSCs has been a great challenge. We hypothesized some key environmental factors are missing in vitro. Therefore, we tried in vivo generation of HSCs from human iPSCs. In this study, we generated human/sheep hematopoietic chimera; that is, sheep that have human HSCs derived from human iPSCs. Human iPSCs were cultured on murine stromal OP9 cells with multiple cytokines for 6 days for differentiation to a hematopoietic lineage. The cells were then transplanted into the liver of busulfan-conditioned fetal sheep. The engraftment of human hematopoietic cells was quantitatively evaluated by PCR of colony-forming units. Considering that many researchers have long failed to generate engraftable HSCs from human iPSCs, the data here imply that the acquisition of hematopoietic engraftment ability of human iPSCs may depend on the in vivo microenvironment such as in the fetal sheep liver. We are now taking out human HSCs from the sheep.

Free Research Field

血液内科学