Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation
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 tumorige...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04995-9 |
| _version_ | 1797806604404391936 |
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| author | Miho Isoda Tsukasa Sanosaka Ryo Tomooka Yo Mabuchi Munehisa Shinozaki Tomoko Andoh-Noda Satoe Banno Noriko Mizota Ryo Yamaguchi Hideyuki Okano Jun Kohyama |
| author_facet | Miho Isoda Tsukasa Sanosaka Ryo Tomooka Yo Mabuchi Munehisa Shinozaki Tomoko Andoh-Noda Satoe Banno Noriko Mizota Ryo Yamaguchi Hideyuki Okano Jun Kohyama |
| author_sort | Miho Isoda |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:09:47Z |
| format | Article |
| id | doaj.art-cfe8d14e05724bbf98a625f354acb147 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-13T06:09:47Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-cfe8d14e05724bbf98a625f354acb1472023-06-11T11:22:51ZengNature PortfolioCommunications Biology2399-36422023-06-016111510.1038/s42003-023-04995-9Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantationMiho Isoda0Tsukasa Sanosaka1Ryo Tomooka2Yo Mabuchi3Munehisa Shinozaki4Tomoko Andoh-Noda5Satoe Banno6Noriko Mizota7Ryo Yamaguchi8Hideyuki Okano9Jun Kohyama10Department of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineDepartment of Physiology, Keio University School of MedicineAbstract 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.https://doi.org/10.1038/s42003-023-04995-9 |
| spellingShingle | Miho Isoda Tsukasa Sanosaka Ryo Tomooka Yo Mabuchi Munehisa Shinozaki Tomoko Andoh-Noda Satoe Banno Noriko Mizota Ryo Yamaguchi Hideyuki Okano Jun Kohyama Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation Communications Biology |
| title | Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation |
| title_full | Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation |
| title_fullStr | Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation |
| title_full_unstemmed | Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation |
| title_short | Mesenchymal properties of iPSC-derived neural progenitors that generate undesired grafts after transplantation |
| title_sort | mesenchymal properties of ipsc derived neural progenitors that generate undesired grafts after transplantation |
| url | https://doi.org/10.1038/s42003-023-04995-9 |
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