Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord
Bone marrow stromal cells (MSC) are attractive candidates for developing cell therapies for central nervous system (CNS) disorders. They can be easily obtained, expanded in culture, and promote modest functional recovery following transplantation into animal models of injured or degenerative CNS. Wh...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2005-11-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000005783982594 |
| _version_ | 1819061530777354240 |
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| author | Sharon A. Swanger Birgit Neuhuber B. Timothy Himes Ajay Bakshi Itzhak Fischer Ph.D. |
| author_facet | Sharon A. Swanger Birgit Neuhuber B. Timothy Himes Ajay Bakshi Itzhak Fischer Ph.D. |
| author_sort | Sharon A. Swanger |
| collection | DOAJ |
| description | Bone marrow stromal cells (MSC) are attractive candidates for developing cell therapies for central nervous system (CNS) disorders. They can be easily obtained, expanded in culture, and promote modest functional recovery following transplantation into animal models of injured or degenerative CNS. While syngeneic MSC grafts can be used efficiently, achieving long-term survival of allogeneic MSC grafts has been a challenge. We hypothesize that improved graft survival will enhance the functional recovery promoted by MSC. To improve MSC graft survival, we tested two dosages of the immune suppressant cyclosporin A (CsA) in an allogeneic model. Syngeneic transplantation of MSC where cells survive well without immune suppression was used as a control. Sprague-Dawley rats treated with standard dose (n = 12) or high-dose (n = 12) CsA served as allogeneic hosts; Fisher 344 rats (n = 12) served as syngeneic hosts. MSC were derived from transgenic Fisher 344 rats expressing human placental alkaline phosphatase and were grafted into cervical spinal cord. Animals treated with standard dose CsA showed significant decreases in allograft size 4 weeks posttransplantation; high CsA doses yielded significantly better graft survival 4 and 8 weeks posttransplantation compared to standard CsA. As expected, syngeneic MSC transplants showed good graft survival after 4 and 8 weeks. To investigate MSC graft elimination, we analyzed immune cell infiltration and cell death. Macrophage infiltration was high after 1 week in all groups. After 4 weeks, high-dose CsA and syngeneic animals showed significant reductions in macrophages at the graft site. Few T lymphocytes were detected in any group at each time point. Cell death occurred throughout the study; however, little apoptotic activity was detected. Histochemical analysis revealed no evidence of neural differentiation. These results indicate that allogeneic transplantation with appropriate immune suppression permits long-term survival of MSC; thus, both allogeneic and syngeneic strategies could be utilized in devising novel therapies for CNS injury. |
| first_indexed | 2024-12-21T14:44:21Z |
| format | Article |
| id | doaj.art-a4194131c38044e291c525368db193cc |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-21T14:44:21Z |
| publishDate | 2005-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-a4194131c38044e291c525368db193cc2022-12-21T19:00:04ZengSAGE PublishingCell Transplantation0963-68971555-38922005-11-011410.3727/000000005783982594Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal CordSharon A. Swanger0Birgit Neuhuber1B. Timothy Himes2Ajay Bakshi3Itzhak Fischer Ph.D.4Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USABone marrow stromal cells (MSC) are attractive candidates for developing cell therapies for central nervous system (CNS) disorders. They can be easily obtained, expanded in culture, and promote modest functional recovery following transplantation into animal models of injured or degenerative CNS. While syngeneic MSC grafts can be used efficiently, achieving long-term survival of allogeneic MSC grafts has been a challenge. We hypothesize that improved graft survival will enhance the functional recovery promoted by MSC. To improve MSC graft survival, we tested two dosages of the immune suppressant cyclosporin A (CsA) in an allogeneic model. Syngeneic transplantation of MSC where cells survive well without immune suppression was used as a control. Sprague-Dawley rats treated with standard dose (n = 12) or high-dose (n = 12) CsA served as allogeneic hosts; Fisher 344 rats (n = 12) served as syngeneic hosts. MSC were derived from transgenic Fisher 344 rats expressing human placental alkaline phosphatase and were grafted into cervical spinal cord. Animals treated with standard dose CsA showed significant decreases in allograft size 4 weeks posttransplantation; high CsA doses yielded significantly better graft survival 4 and 8 weeks posttransplantation compared to standard CsA. As expected, syngeneic MSC transplants showed good graft survival after 4 and 8 weeks. To investigate MSC graft elimination, we analyzed immune cell infiltration and cell death. Macrophage infiltration was high after 1 week in all groups. After 4 weeks, high-dose CsA and syngeneic animals showed significant reductions in macrophages at the graft site. Few T lymphocytes were detected in any group at each time point. Cell death occurred throughout the study; however, little apoptotic activity was detected. Histochemical analysis revealed no evidence of neural differentiation. These results indicate that allogeneic transplantation with appropriate immune suppression permits long-term survival of MSC; thus, both allogeneic and syngeneic strategies could be utilized in devising novel therapies for CNS injury.https://doi.org/10.3727/000000005783982594 |
| spellingShingle | Sharon A. Swanger Birgit Neuhuber B. Timothy Himes Ajay Bakshi Itzhak Fischer Ph.D. Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord Cell Transplantation |
| title | Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord |
| title_full | Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord |
| title_fullStr | Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord |
| title_full_unstemmed | Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord |
| title_short | Analysis of Allogeneic and Syngeneic Bone Marrow Stromal Cell Graft Survival in the Spinal Cord |
| title_sort | analysis of allogeneic and syngeneic bone marrow stromal cell graft survival in the spinal cord |
| url | https://doi.org/10.3727/000000005783982594 |
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