リプログラミング因子導入、細胞間融合、細胞質融合のリプログラミング効率の比較
南カリフォルニア大学の長谷川光一先生らのグループによって、リプログラミング因子導入によるヒトiPS細胞樹立、ヒトES細胞と体細胞間での細胞融合、ヒトES細胞細胞質と体細胞の融合のリプログラミング効率を比較したという論文が発表されました。
iPS細胞樹立の場合、4週間以上かかり、効率は0.001%以下だったのに対し、細胞融合の場合では、10日以内で0.005%以上だったのに加え、部分的なリプログラミングを受けたコロニーはほとんど現れない、細胞質融合の場合は、リプログラミングは始まるものの、完全にリプログラミングされることはなかったとのこと。
また、一時的にリプログラミング因子を導入後、ヒトES細胞と融合させることでリプログラミング効率が向上することも示しています。
Stem Cells. 2010 Jun 22. [Epub ahead of print]
Comparison of Reprogramming Efficiency Between Transduction of Reprogramming Factors, Cell-Cell Fusion, and Cytoplast Fusion.
Hasegawa K, Zhang P, Wei Z, Pomeroy JE, Lu W, Pera MF.
http://www.ncbi.nlm.nih.gov/pubmed/20572011?dopt=Abstract
Reprogramming human somatic cells into pluripotent cells opens up new possibilities for transplantation therapy, the study of disease, and drug screening. In addition to somatic cell nuclear transfer, several approaches to reprogramming human cells have been reported: transduction of defined transcription factors to generate induced pluripotent stem cell (iPSC), human embryonic stem cell (hESC)-somatic cell fusion, and hESC cytoplast-somatic cell fusion or exposure to extracts of hESC. Here we optimized techniques for hESC-human fibroblast fusion, and enucleation and cytoplast fusion, and then compared the reprogramming efficiency between iPSC generation, cell-fusion and cytoplast-fusion. Compared to iPSC, hESC-fusion provided for much faster and efficient reprogramming of somatic cells. The reprogramming required more than 4 weeks and the efficiency was less than 0.001% in iPSC generation, and it was less than 10 days and more than 0.005% in hESC-fusion. In addition, fusion yielded almost no partially reprogrammed cell colonies. However, the fused cells were tetraploid or aneuploid. hESC cytoplast fusion could initiate reprogramming but was never able to complete reprogramming. These data indicate that in cell fusion, as in nuclear transfer, reprogramming through direct introduction of a somatic nucleus into the environment of a pluripotent cell provides for relatively efficient reprogramming. The findings also suggest that the nucleus of the host pluripotent cell may contain components that accelerate the reprogramming process.