Cargando…
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...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093920/ https://www.ncbi.nlm.nih.gov/pubmed/37047179 http://dx.doi.org/10.3390/ijms24076205 |
_version_ | 1785023712278347776 |
---|---|
author | Chen, Lu Yang, Jing Klassen, Henry |
author_facet | Chen, Lu Yang, Jing Klassen, Henry |
author_sort | Chen, Lu |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10093920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100939202023-04-13 Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice Chen, Lu Yang, Jing Klassen, Henry Int J Mol Sci Article 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. MDPI 2023-03-25 /pmc/articles/PMC10093920/ /pubmed/37047179 http://dx.doi.org/10.3390/ijms24076205 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Lu Yang, Jing Klassen, Henry Immune Responses to Sequential Binocular Transplantation of Allogeneic Retinal Progenitor Cells to the Vitreous Cavity in Mice |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093920/ https://www.ncbi.nlm.nih.gov/pubmed/37047179 http://dx.doi.org/10.3390/ijms24076205 |
work_keys_str_mv | AT chenlu immuneresponsestosequentialbinoculartransplantationofallogeneicretinalprogenitorcellstothevitreouscavityinmice AT yangjing immuneresponsestosequentialbinoculartransplantationofallogeneicretinalprogenitorcellstothevitreouscavityinmice AT klassenhenry immuneresponsestosequentialbinoculartransplantationofallogeneicretinalprogenitorcellstothevitreouscavityinmice |