論文

国際誌
2021年3月12日

Vinblastine treatment decreases the undifferentiated cell contamination of human iPSC-derived intestinal epithelial-like cells.

Molecular therapy. Methods & clinical development
  • Moe Ichikawa
  • ,
  • Ryosuke Negoro
  • ,
  • Kanae Kawai
  • ,
  • Tomoki Yamashita
  • ,
  • Kazuo Takayama
  • ,
  • Hiroyuki Mizuguchi

20
開始ページ
463
終了ページ
472
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.omtm.2021.01.005

Human induced pluripotent stem cell-derived intestinal epithelial cells (hiPSC-IECs) are expected to be utilized in regenerative medicine. To perform a safe transplantation without the risk of tumor formation, residual undifferentiated hiPSCs must be removed from hiPSC-IECs. In this study, we examined whether vinblastine (a multiple drug resistance 1 [MDR1] substrate) could remove residual undifferentiated hiPSCs in hiPSC-IECs and attempted to generate hiPSC-IECs applicable to transplantation medicine. We found that the expression levels of pluripotent markers were largely decreased and those of intestinal markers were increased by vinblastine treatment. The treatment of undifferentiated hiPSCs with vinblastine significantly decreased their viability. These results suggested that undifferentiated hiPSCs can be eliminated from hiPSC-IECs by vinblastine treatment. We hypothesized that MDR1-negative cells (such as undifferentiated hiPSCs) die upon vinblastine treatment because they are unable to excrete vinblastine. As expected, the cell viability of MDR1-knockout hiPSC-IECs was significantly decreased by vinblastine treatment. Furthermore, teratomas were formed by subcutaneous transplantation of hiPSC-IECs mixed with undifferentiated hiPSCs into mice, but they were not observed when the transplanted cells were pre-treated with vinblastine. Vinblastine-treated hiPSC-IECs would be an effective cell source for safe regenerative medicine.

リンク情報
DOI
https://doi.org/10.1016/j.omtm.2021.01.005
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33614822
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868938
ID情報
  • DOI : 10.1016/j.omtm.2021.01.005
  • PubMed ID : 33614822
  • PubMed Central 記事ID : PMC7868938

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