Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice
Intravitreal transplantation of allogeneic human retinal progenitor cells (hRPCs) holds promise as a treatment for blinding retinal degenerations. Prior work has shown that neural progenitors are well-tolerated as allografts following single injections; however, sequential delivery of allogeneic cel...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6205 |
| _version_ | 1797607913073672192 |
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| author | Lu Chen Jing Yang Henry Klassen |
| author_facet | Lu Chen Jing Yang Henry Klassen |
| author_sort | Lu Chen |
| collection | DOAJ |
| description | Intravitreal transplantation of allogeneic human retinal progenitor cells (hRPCs) holds promise as a treatment for blinding retinal degenerations. Prior work has shown that neural progenitors are well-tolerated as allografts following single injections; however, sequential delivery of allogeneic cells raises the potential risk of host sensitization with subsequent immune rejection of grafts. The current study was designed to assess whether an immune response would be induced by repeated intravitreal transplants of allogeneic RPCs utilizing the mouse animal model. We injected murine retinal progenitor cells (gmRPCs), originally derived from donors with a C57BL/6 genetic background, into BALB/c recipient mice in order to provide safety data as to what might be expected following repeated treatment of patients with allogeneic human cell product. Immune responses to gmRPCs were mild, consisting of T cells, B cells, neutrophils, and natural killer cells, with macrophages clearly the predominating. Animals treated with repeat doses of gmRPCs did not show evidence of sensitization, nor was there immune-mediated destruction of the grafts. Despite the absence of immunosuppressive treatments, allogeneic gmRPC grafts survived following repeat dosing, thus providing support for the preliminary observation that repeated injection of allogeneic RPCs to the vitreous cavity is tolerated in patients with retinitis pigmentosa. |
| first_indexed | 2024-03-11T05:36:13Z |
| format | Article |
| id | doaj.art-cd734988f8604483b01f0ca55368cab2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:13Z |
| publishDate | 2023-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cd734988f8604483b01f0ca55368cab22023-11-17T16:47:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247620510.3390/ijms24076205Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in MiceLu Chen0Jing Yang1Henry Klassen2Department of Ophthalmology, University of California, 845 Health Sciences Road, Irvine, CA 92697, USADepartment of Ophthalmology, University of California, 845 Health Sciences Road, Irvine, CA 92697, USADepartment of Ophthalmology, University of California, 845 Health Sciences Road, Irvine, CA 92697, USAIntravitreal transplantation of allogeneic human retinal progenitor cells (hRPCs) holds promise as a treatment for blinding retinal degenerations. Prior work has shown that neural progenitors are well-tolerated as allografts following single injections; however, sequential delivery of allogeneic cells raises the potential risk of host sensitization with subsequent immune rejection of grafts. The current study was designed to assess whether an immune response would be induced by repeated intravitreal transplants of allogeneic RPCs utilizing the mouse animal model. We injected murine retinal progenitor cells (gmRPCs), originally derived from donors with a C57BL/6 genetic background, into BALB/c recipient mice in order to provide safety data as to what might be expected following repeated treatment of patients with allogeneic human cell product. Immune responses to gmRPCs were mild, consisting of T cells, B cells, neutrophils, and natural killer cells, with macrophages clearly the predominating. Animals treated with repeat doses of gmRPCs did not show evidence of sensitization, nor was there immune-mediated destruction of the grafts. Despite the absence of immunosuppressive treatments, allogeneic gmRPC grafts survived following repeat dosing, thus providing support for the preliminary observation that repeated injection of allogeneic RPCs to the vitreous cavity is tolerated in patients with retinitis pigmentosa.https://www.mdpi.com/1422-0067/24/7/6205stem cellsimmune toleranceimmune privilegegraft rejectionintravitreal injection |
| spellingShingle | Lu Chen Jing Yang Henry Klassen Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice International Journal of Molecular Sciences stem cells immune tolerance immune privilege graft rejection intravitreal injection |
| title | Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice |
| title_full | Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice |
| title_fullStr | Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice |
| title_full_unstemmed | Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice |
| title_short | Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice |
| title_sort | immune responses to sequential binocular transplantation of allogeneic retinal progenitor cells to the vitreous cavity in mice |
| topic | stem cells immune tolerance immune privilege graft rejection intravitreal injection |
| url | https://www.mdpi.com/1422-0067/24/7/6205 |
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