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

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...

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Bibliographic Details
Published in:Communications biology 2023-06, Vol.6 (1), p.611-611, Article 611
Main Authors: Isoda, Miho, Sanosaka, Tsukasa, Tomooka, Ryo, Mabuchi, Yo, Shinozaki, Munehisa, Andoh-Noda, Tomoko, Banno, Satoe, Mizota, Noriko, Yamaguchi, Ryo, Okano, Hideyuki, Kohyama, Jun
Format: Article
Language:English
Subjects:
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Biology
Biomedical and Life Sciences
Carcinogenesis - metabolism
CD105 antigen
CD73 antigen
Cell differentiation
Cell Transformation, Neoplastic - metabolism
Humans
Induced Pluripotent Stem Cells
Life Sciences
Neural cell adhesion molecule
Neural stem cells
Neural Stem Cells - metabolism
Osteogenesis
Pluripotency
Progenitor cells
Regenerative medicine
Stem cells
Transcriptomes
Transplantation
Tumorigenesis
Tumorigenicity
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Summary: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. A single cell-based approach to characterize human induced pluripotent stem cells resistant to differentiation finds cellular properties of neural and mesenchymal origins, pointing at underlying causes for undesired grafts after transplantation.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-04995-9