Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation

Miho Isoda, Tsukasa Sanosaka, Ryo Tomooka, Yo Mabuchi, Munehisa Shinozaki, Tomoko Andoh-Noda, Satoe Banno, Noriko Mizota, Ryo Yamaguchi, Hideyuki Okano, Jun Kohyama

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Although neural stem/progenitor cells derived from human induced pluripotent stem cells (hiPSC-NS/PCs) are expected to be a cell source for cell-based therapy, tumorigenesis of hiPSC-NS/PCs is a potential problem for clinical applications. Therefore, to understand the mechanisms of tumorigenicity in NS/PCs, we clarified the cell populations of NS/PCs. We established single cell-derived NS/PC clones (scNS/PCs) from hiPSC-NS/PCs that generated undesired grafts. Additionally, we performed bioassays on scNS/PCs, which classified cell types within parental hiPSC-NS/PCs. Interestingly, we found unique subsets of scNS/PCs, which exhibited the transcriptome signature of mesenchymal lineages. Furthermore, these scNS/PCs expressed both neural (PSA-NCAM) and mesenchymal (CD73 and CD105) markers, and had an osteogenic differentiation capacity. Notably, eliminating CD73+ CD105+ cells from among parental hiPSC-NS/PCs ensured the quality of hiPSC-NS/PCs. Taken together, the existence of unexpected cell populations among NS/PCs may explain their tumorigenicity leading to potential safety issues of hiPSC-NS/PCs for future regenerative medicine.

Original languageEnglish
Article number611
JournalCommunications biology
Volume6
Issue number1
DOIs
Publication statusPublished - 12-2023

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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