Exploit of an alternative stem cell transplantation in utero based on feto-maternal tolerance using allogeneic donor cells immunologically matched to the mother.
| Project/Area Number |
26670515
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Ihara Norimasa 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, その他 (50425716)
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| Co-Investigator(Kenkyū-buntansha) |
梅澤 明弘 国立研究開発法人国立成育医療研究センター, 再生医療センター, 副所長/再生医療センター長 (70213486)
阿久津 英憲 国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225)
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| Research Collaborator |
ONAMI Naoko
TSUMURA Hideki
INOUE Eisuke
HAYASHI Satoshi
SAGO Haruhiko
MIZUTANI Shuki
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 胎児治療 / 免疫寛容 / 造血幹細胞移植 / 先天性代謝異常症 / microchimerism / 非遺伝母由来HLA抗原 / 細胞移植 |
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| Outline of Final Research Achievements |
In utero stem cell transplantation (IUSCT) has been performed in fetuses with a normal immune response, but a lifelong engraftment of allogeneic donor cells has been barely achieved. Recent studies have reported that the mechanism of immunological barriers was due to maternal responses. From this point of view, maternal cells would be advantageous as donor cells, and they are also favorable for IUSCT because immunoreactions do not occur in the mother.
We performed in vitro fertilization in a MPSVII murine model and transferred affected embryos to ICR/B6-GFP surrogate mothers in cases where fetuses receiving IUSCT were all homozygous. Lineage-depleted cells from ICR/B6-GFP mice were injected intravenously. Donor cells in chimeric mice from ICR/B6-GFP mothers were detected at death, and were confirmed in several tissues including the brains of sacrificed chimeric mice. Furthermore, improvement of bone structure and rescue of reproductive ability were confirmed in our preclinical study.
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] ATM regulates adipocyte differentiation and contributes to glucose homeostasis.2015
Author(s)
Takagi M., Uno M., Nishii R., Sugimoto M., Hasegawa S., Piao J., Ihara N., Kanai S., Kakei S., Tamura Y., Suganami T., Kamei Y., Shimizu T., Yasuda A., Ogawa Y., Mizutani S.
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Journal Title
Cell Reports
Volume: 10
Issue: 6
Pages: 957-967
DOI
Related Report
Peer Reviewed / Open Access
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