はじめに, ヒトiPS細胞から分化誘導した神経幹細胞(NSC)にウイルスベクターを用いてHSV-tK遺伝子を導入した。脳腫瘍モデルマウスにHSV-tk発現NSCを移植し, Ganciclovir(GCV)を投与したところ, 著明な治療効果が認められた。つぎにゲノム編集によりHSV-tk遺伝子をiPSに導入したところ, 細胞毒性により安定したiPS細胞株が樹立できなかった。そこで, 遺伝子発現誘導システムを用いて, Tet-inducible HSV-tk導入iPS細胞を樹立した。治療用NSCを誘導し, 脳腫瘍モデルマウスに移植後, GCVとDoxycyclineを投与すると, 著明な治療効果が確認された。
In this study, the HSV-tK gene was firstly transduced into neural stem cells (NSCs) differentiated from human iPS cells using a viral vector. HSV-tk expressing iPS-NSCs were transplanted into human brain tumor model mice, and the effectiveness of this therapy by administration of ganciclovir (GCV) was demonstrated. Next, HSV-tk gene was introduced into iPS by genome editing, but HSV-tk expressing iPS cell line could not be established due to cytotoxicity. Then, Tet-inducible HSV-tk transduced iPS cells were established using gene expression induction system. After induction of differentiation into therapeutic NSCs, these NSCs were transplanted into brain tumor model mice. After administration of GCV with Doxycycline, a remarkable therapeutic effect of this therapy using gene expression induction system was confirmed.
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