Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy
The development of a safeguard system to remove tumorigenic cells would allow safer clinical applications of stem cells for the treatment of patients with an intractable disease including genetic disorders. Such safeguard systems should not disrupt the host genome and should have long-term stability...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116300580 |
| _version_ | 1818353727158878208 |
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| author | Narumi Uno Katsuhiro Uno Shinya Komoto Teruhiko Suzuki Masaharu Hiratsuka Mitsuhiko Osaki Yasuhiro Kazuki Mitsuo Oshimura |
| author_facet | Narumi Uno Katsuhiro Uno Shinya Komoto Teruhiko Suzuki Masaharu Hiratsuka Mitsuhiko Osaki Yasuhiro Kazuki Mitsuo Oshimura |
| author_sort | Narumi Uno |
| collection | DOAJ |
| description | The development of a safeguard system to remove tumorigenic cells would allow safer clinical applications of stem cells for the treatment of patients with an intractable disease including genetic disorders. Such safeguard systems should not disrupt the host genome and should have long-term stability. Here, we attempted to develop a tumor-suppressing mammalian artificial chromosome containing a safeguard system that uses the immune rejection system against allogeneic tissue from the host. For proof-of-concept of the safeguard system, B16F10 mouse melanoma cells expressing the introduced H2-K(d) major histocompatibility complex (MHC class I)-allogenic haplotype were transplanted into recipient C57BL/6J mice expressing MHC H2-K(b). Subcutaneous implantation of B16F10 cells into C57BL/6J mice resulted in high tumorigenicity. The volume of tumors derived from B16F10 cells expressing allogenic MHC H2-K(d) was decreased significantly (P < 0.01). Suppression of MHC H2-K(d)-expressing tumors in C57BL/6J mice was enhanced by immunization with MHC H2-K(d)-expressing splenocytes (P < 0.01). These results suggest that the safeguard system is capable of suppressing tumor formation by the transplanted cells. |
| first_indexed | 2024-12-13T19:14:07Z |
| format | Article |
| id | doaj.art-d3b6c4d8a36f4b76862cafa9a6b81f7a |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-13T19:14:07Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-d3b6c4d8a36f4b76862cafa9a6b81f7a2022-12-21T23:34:20ZengElsevierMolecular Therapy: Nucleic Acids2162-25312015-01-014C10.1038/mtna.2015.45Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell TherapyNarumi Uno0Katsuhiro Uno1Shinya Komoto2Teruhiko Suzuki3Masaharu Hiratsuka4Mitsuhiko Osaki5Yasuhiro Kazuki6Mitsuo Oshimura7Chromosome Engineering Research Center, Tottori University, Yonago, JapanDepartment of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, JapanDepartment of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, JapanStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanDepartment of Molecular and Cellular Biology, Faculty of Medicine, Tottori University, Yonago, JapanDivision of Pathological Biochemistry, Faculty of Medicine, Tottori University, Yonago, JapanChromosome Engineering Research Center, Tottori University, Yonago, JapanChromosome Engineering Research Center, Tottori University, Yonago, JapanThe development of a safeguard system to remove tumorigenic cells would allow safer clinical applications of stem cells for the treatment of patients with an intractable disease including genetic disorders. Such safeguard systems should not disrupt the host genome and should have long-term stability. Here, we attempted to develop a tumor-suppressing mammalian artificial chromosome containing a safeguard system that uses the immune rejection system against allogeneic tissue from the host. For proof-of-concept of the safeguard system, B16F10 mouse melanoma cells expressing the introduced H2-K(d) major histocompatibility complex (MHC class I)-allogenic haplotype were transplanted into recipient C57BL/6J mice expressing MHC H2-K(b). Subcutaneous implantation of B16F10 cells into C57BL/6J mice resulted in high tumorigenicity. The volume of tumors derived from B16F10 cells expressing allogenic MHC H2-K(d) was decreased significantly (P < 0.01). Suppression of MHC H2-K(d)-expressing tumors in C57BL/6J mice was enhanced by immunization with MHC H2-K(d)-expressing splenocytes (P < 0.01). These results suggest that the safeguard system is capable of suppressing tumor formation by the transplanted cells.http://www.sciencedirect.com/science/article/pii/S2162253116300580cancer immunotherapygene and cell therapyHACMACmajor histocompatibility complexmammalian artificial chromosomepluripotent stem cellregenerative medicinesafeguard systemtumor suppression |
| spellingShingle | Narumi Uno Katsuhiro Uno Shinya Komoto Teruhiko Suzuki Masaharu Hiratsuka Mitsuhiko Osaki Yasuhiro Kazuki Mitsuo Oshimura Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy Molecular Therapy: Nucleic Acids cancer immunotherapy gene and cell therapy HAC MAC major histocompatibility complex mammalian artificial chromosome pluripotent stem cell regenerative medicine safeguard system tumor suppression |
| title | Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy |
| title_full | Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy |
| title_fullStr | Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy |
| title_full_unstemmed | Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy |
| title_short | Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy |
| title_sort | development of a safeguard system using an episomal mammalian artificial chromosome for gene and cell therapy |
| topic | cancer immunotherapy gene and cell therapy HAC MAC major histocompatibility complex mammalian artificial chromosome pluripotent stem cell regenerative medicine safeguard system tumor suppression |
| url | http://www.sciencedirect.com/science/article/pii/S2162253116300580 |
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