論文

国際誌
2024年4月16日

Identification and removal of unexpected proliferative off-target cells emerging after iPSC-derived pancreatic islet cell implantation.

Proceedings of the National Academy of Sciences of the United States of America
  • Hideyuki Hiyoshi
  • Kensuke Sakuma
  • Shinya Asano
  • Stephanie C Napier
  • Shuhei Konagaya
  • Taisuke Mochida
  • Hikaru Ueno
  • Takeshi Watanabe
  • Yoshiaki Kassai
  • Hirokazu Matsumoto
  • Ryo Ito
  • Taro Toyoda
  • 全て表示

121
16
開始ページ
e2320883121
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.2320883121

Differentiation of pancreatic endocrine cells from human pluripotent stem cells (PSCs) has been thoroughly investigated for application in cell therapy against diabetes. In the context of induced pancreatic endocrine cell implantation, previous studies have reported graft enlargement resulting from off-target pancreatic lineage cells. However, there is currently no documented evidence of proliferative off-target cells beyond the pancreatic lineage in existing studies. Here, we show that the implantation of seven-stage induced PSC-derived pancreatic islet cells (s7-iPICs) leads to the emergence of unexpected off-target cells with proliferative capacity via in vivo maturation. These cells display characteristics of both mesenchymal stem cells (MSCs) and smooth muscle cells (SMCs), termed proliferative MSC- and SMC-like cells (PMSCs). The frequency of PMSC emergence was found to be high when 108 s7-iPICs were used. Given that clinical applications involve the use of a greater number of induced cells than 108, it is challenging to ensure the safety of clinical applications unless PMSCs are adequately addressed. Accordingly, we developed a detection system and removal methods for PMSCs. To detect PMSCs without implantation, we implemented a 4-wk-extended culture system and demonstrated that putative PMSCs could be reduced by compound treatment, particularly with the taxane docetaxel. When docetaxel-treated s7-iPICs were implanted, the PMSCs were no longer observed. This study provides useful insights into the identification and resolution of safety issues, which are particularly important in the field of cell-based medicine using PSCs.

リンク情報
DOI
https://doi.org/10.1073/pnas.2320883121
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/38598342
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032438
ID情報
  • DOI : 10.1073/pnas.2320883121
  • PubMed ID : 38598342
  • PubMed Central 記事ID : PMC11032438

エクスポート
BibTeX RIS