Stem cell transplantation for fetal therapy

• Project/Area Number: 22791044
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Embryonic/Neonatal medicine
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: IHARA Norimasa 独立行政法人国立成育医療研究センター, 生殖・細胞医療研究部, 研究員 (50425716)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 胎児治療 / 幹細胞移植 / 免疫寛容 / キメリズム / 先天性代謝異常症 / 子宮内幹細胞移植 / 間葉系幹細胞 / 完全ヒト型培養システム

Research Abstract

We performed allogeneic in utero stem cell transplantation (IUT) at E14.5 from MHC-H2Kb+GFP+ C57BL/6TgN(act-EGFP) mouse donors into MHC-H2Kd+ BALB/c recipient fetuses. Donor mononuclear cells were injected intravenously into each fetus. At 4 weeks of age, peripheral blood hematopoietic chimerism was determined by flow cytometry, and we achieved about 20% of donor chimerism. In a hereditary disorder, donor cells can supply the missing enzyme continuously. Even low level of secretion of the enzyme reduces lysosomal storage. This indicates that IUT would be effective therapy for diseases especially in which brain damage and bone aplasia progress during early stage of development.