The Anterior Eye Chamber as a Visible Medium for In Vivo Tumorigenicity Tests

Emi Inagaki, Eri Arai, Shin Hatou, Tomoko Sayano, Hiroko Taniguchi, Kazuno Negishi, Yae Kanai, Yasunori Sato, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura

Research output: Contribution to journalArticlepeer-review

Abstract

Pluripotent stem cell (PSC)-based cell therapies have increased steadily over the past few years, and assessing the risk of tumor formation is a high priority for clinical studies. Current in vivo tumorigenesis studies require several months and depend strongly on the site of grafting. In this study, we report that the anterior eye chamber is preferable to the subcutaneous space for in vivo tumorigenesis studies for several reasons. First, cells can easily be transplanted into the anterior chamber and monitored in real-time without sacrificing the animals due to the transparency of the cornea. Second, tumor formation is faster than with the conventional subcutaneous method. The median tumor formation time in the subcutaneous area was 18.50 weeks (95% CI 10.20-26.29), vs. 4.0 weeks (95% CI 3.34-.67) in the anterior chamber (P = .0089). When hiPSCs were spiked with fibroblasts, the log10TPD50 was 3.26, compared with 4.99 when hiPSCs were transplanted without fibroblasts. There was more than a 40-fold difference in the log10TPD50 values with fibroblasts. Furthermore, the log10TPD50 for HeLa cells was 1.45 and 100% of animals formed tumors at a concentration greater than 0.1%, indicating that the anterior chamber tumorigenesis assays can be applied for cancer cell lines as well. Thus, our method has the potential to become a powerful tool in all areas of tumorigenesis studies and cancer research.

Original languageEnglish
Pages (from-to)841-849
Number of pages9
JournalStem Cells Translational Medicine
Volume11
Issue number8
DOIs
Publication statusPublished - 2022 Aug 23

Keywords

  • anterior chamber
  • induced pluripotent stem cells
  • regenerative medicine
  • teratoma formation assay

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'The Anterior Eye Chamber as a Visible Medium for In Vivo Tumorigenicity Tests'. Together they form a unique fingerprint.

Cite this