RRC ID 71729
Author Inagaki E, Arai E, Hatou S, Sayano T, Taniguchi H, Negishi K, Kanai Y, Sato Y, Okano H, Tsubota K, Shimmura S.
Title The Anterior Eye Chamber as a Visible Medium for In Vivo Tumorigenicity Tests.
Journal Stem Cells Transl Med
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.
Volume 11(8)
Pages 841-849
Published 2022-8-23
DOI 10.1093/stcltm/szac036
PII 6603359
PMID 35666752
PMC PMC9397653
MeSH Animals Anterior Chamber Carcinogenesis / pathology Carcinogenicity Tests Cell Transformation, Neoplastic / pathology HeLa Cells Humans Induced Pluripotent Stem Cells* / metabolism
IF 6.429
Resource
Human and Animal Cells HeLa(RCB0007)