Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection
Recent studies have demonstrated that transplantation of induced pluripotent stem cell-derived neurospheres can promote functional recovery after spinal cord injury in rodents, as well as in nonhuman primates. However, the potential tumorigenicity of the transplanted cells remains a matter of appreh...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2015-07-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368914X681711 |
| _version_ | 1818923986373836800 |
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| author | Go Itakura Yoshiomi Kobayashi Soraya Nishimura Hiroki Iwai Morito Takano Akio Iwanami Yoshiaki Toyama Hideyuki Okano Masaya Nakamura |
| author_facet | Go Itakura Yoshiomi Kobayashi Soraya Nishimura Hiroki Iwai Morito Takano Akio Iwanami Yoshiaki Toyama Hideyuki Okano Masaya Nakamura |
| author_sort | Go Itakura |
| collection | DOAJ |
| description | Recent studies have demonstrated that transplantation of induced pluripotent stem cell-derived neurospheres can promote functional recovery after spinal cord injury in rodents, as well as in nonhuman primates. However, the potential tumorigenicity of the transplanted cells remains a matter of apprehension prior to clinical applications. As a first step to overcome this concern, this study established a glioblastoma multiforme xenograft model mouse. The feasibility of controlling immune suppression to ablate the grafted cells was then investigated. The human glioblastoma multiforme cell line U251 MG was transplanted into the intact spinal cords of immunodeficient NOD/SCID mice or into those of immunocompetent C57BL/6J H-2kb mice treated with or without immunosuppressants [FK506 plus anticluster of differentiation (CD) 4 antibody (Ab), or FK506 alone]. In vivo bioluminescent imaging was used to evaluate the chronological survival of the transplanted cells. The graft survival rate was 100% ( n = 9/9) in NOD/SCID mice, 0% ( n = 6/6) in C57BL/6J mice without immunosuppressant treatment, and 100% ( n = 37/37) in C57BL6/J mice with immunosuppressant treatment. After confirming the growth of the grafted cells in the C57/BL6J mice treated with immunosuppressants, immune suppression was discontinued. The grafted cells were subsequently rejected within 3 days in C57BL/6J mice treated with FK506 alone, as opposed to 26 days in C57BL/6J mice treated with FK506 plus anti-CD4 Ab. Histological evaluation confirmed the ablation of the grafted cells. Although this work describes a xenograft setting, the results suggest that this immunomodulatory strategy could provide a safety lock against tumor formation stemming from transplanted cells. |
| first_indexed | 2024-12-20T02:18:09Z |
| format | Article |
| id | doaj.art-07ddb6b5940c4d5cb5486ab51bf74099 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-20T02:18:09Z |
| publishDate | 2015-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-07ddb6b5940c4d5cb5486ab51bf740992022-12-21T19:56:52ZengSAGE PublishingCell Transplantation0963-68971555-38922015-07-012410.3727/096368914X681711Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of ImmunorejectionGo Itakura0Yoshiomi Kobayashi1Soraya Nishimura2Hiroki Iwai3Morito Takano4Akio Iwanami5Yoshiaki Toyama6Hideyuki Okano7Masaya Nakamura8Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JapanRecent studies have demonstrated that transplantation of induced pluripotent stem cell-derived neurospheres can promote functional recovery after spinal cord injury in rodents, as well as in nonhuman primates. However, the potential tumorigenicity of the transplanted cells remains a matter of apprehension prior to clinical applications. As a first step to overcome this concern, this study established a glioblastoma multiforme xenograft model mouse. The feasibility of controlling immune suppression to ablate the grafted cells was then investigated. The human glioblastoma multiforme cell line U251 MG was transplanted into the intact spinal cords of immunodeficient NOD/SCID mice or into those of immunocompetent C57BL/6J H-2kb mice treated with or without immunosuppressants [FK506 plus anticluster of differentiation (CD) 4 antibody (Ab), or FK506 alone]. In vivo bioluminescent imaging was used to evaluate the chronological survival of the transplanted cells. The graft survival rate was 100% ( n = 9/9) in NOD/SCID mice, 0% ( n = 6/6) in C57BL/6J mice without immunosuppressant treatment, and 100% ( n = 37/37) in C57BL6/J mice with immunosuppressant treatment. After confirming the growth of the grafted cells in the C57/BL6J mice treated with immunosuppressants, immune suppression was discontinued. The grafted cells were subsequently rejected within 3 days in C57BL/6J mice treated with FK506 alone, as opposed to 26 days in C57BL/6J mice treated with FK506 plus anti-CD4 Ab. Histological evaluation confirmed the ablation of the grafted cells. Although this work describes a xenograft setting, the results suggest that this immunomodulatory strategy could provide a safety lock against tumor formation stemming from transplanted cells.https://doi.org/10.3727/096368914X681711 |
| spellingShingle | Go Itakura Yoshiomi Kobayashi Soraya Nishimura Hiroki Iwai Morito Takano Akio Iwanami Yoshiaki Toyama Hideyuki Okano Masaya Nakamura Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection Cell Transplantation |
| title | Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection |
| title_full | Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection |
| title_fullStr | Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection |
| title_full_unstemmed | Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection |
| title_short | Control of the Survival and Growth of Human Glioblastoma Grafted into the Spinal Cord of Mice by Taking Advantage of Immunorejection |
| title_sort | control of the survival and growth of human glioblastoma grafted into the spinal cord of mice by taking advantage of immunorejection |
| url | https://doi.org/10.3727/096368914X681711 |
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