論文 - 詳細
| RRC ID | 38566 |
|---|---|
| 著者 | Abe T, Masuda S, Ban H, Hayashi S, Ueda Y, Inoue M, Hasegawa M, Nagao Y, Hanazono Y. |
| タイトル | Ex vivo expansion of human HSCs with Sendai virus vector expressing HoxB4 assessed by sheep in utero transplantation. |
| ジャーナル | Exp Hematol |
| Abstract |
OBJECTIVE:The homeobox B4 (HoxB4) gene promotes expansion of hematopoietic stem cells (HSCs). However, frequent development of leukemia in large animals due to retrovirally transduced HoxB4 gene has been reported. To prevent tumorigenesis, we developed a nonintegrating and nonreplicating Sendai virus vector that did not contain the phosphoprotein gene (SeV/ΔP), which enabled clearance of the vector and transgene shortly after transduction. We tested the SeV/ΔP vector expressing the HoxB4 gene (SeV/ΔP/HoxB4) for the ex vivo expansion of human cord blood CD34(+) cells (HSCs) using a sheep in utero transplantation assay. MATERIALS AND METHODS:Human HSCs were ex vivo-expanded by transduction with SeV/ΔP/HoxB4 vector and transplanted into the abdominal cavity of fetal sheep. The engraftment of human HSCs in the lambs was quantitatively evaluated by hematopoietic colony-forming unit assays. RESULTS:After transplantation, the HoxB4-transduced HSCs contributed to longer-period (up to 20 months) repopulation in sheep, and human hematopoietic progenitors were detected more frequently in the bone marrow of the HoxB4 group as compared with the control untreated group (p < 0.05). The expansion of human HSCs with the SeV/ΔP/HoxB4 vector was comparable with previously reported retroviral vectors expressing HoxB4. The SeV/ΔP/HoxB4 vector and the transgene were cleared from the recipient sheep and leukemia was not detected at 20 months post-transplantation. CONCLUSIONS:The SeV/ΔP vector would be suitable for transient expression of HoxB4 in human CD34(+) cells. In addition, the SeV/ΔP vector is free of concern about transgene-related and insertional leukemogenesis and should be safer than retroviral vectors. |
| 巻・号 | 39(1) |
| ページ | 47-54 |
| 公開日 | 2011-1-1 |
| DOI | 10.1016/j.exphem.2010.09.007 |
| PII | S0301-472X(10)00486-8 |
| PMID | 20875838 |
| MeSH | Animals Base Sequence DNA Primers Female Genetic Vectors* Hematopoietic Stem Cells / cytology* Homeodomain Proteins / genetics* Humans Polymerase Chain Reaction Pregnancy Sendai virus / genetics* Sheep Transcription Factors / genetics* Transplantation, Heterologous |
| IF | 2.82 |
| 引用数 | 11 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL HEMATOLOGY |
| リソース情報 | |
| 研究用ヒト臍帯血幹細胞 | |