Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration
Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.871216/full |
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| author | Gustavo dos Santos Rosa André Massahiro Teramoto Krieck Enrico Topan Padula Fernanda de Castro Stievani Mariana Correa Rossi João Pedro Hübbe Pfeifer Roberta Martins Basso Aline Márcia Marques Braz Márjorie de Assis Golim Márjorie de Assis Golim Ana Liz Garcia Alves |
| author_facet | Gustavo dos Santos Rosa André Massahiro Teramoto Krieck Enrico Topan Padula Fernanda de Castro Stievani Mariana Correa Rossi João Pedro Hübbe Pfeifer Roberta Martins Basso Aline Márcia Marques Braz Márjorie de Assis Golim Márjorie de Assis Golim Ana Liz Garcia Alves |
| author_sort | Gustavo dos Santos Rosa |
| collection | DOAJ |
| description | Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients’ sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections. |
| first_indexed | 2024-04-14T05:59:28Z |
| format | Article |
| id | doaj.art-04e02f66b29043c49bb6cf99862c2c69 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T05:59:28Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-04e02f66b29043c49bb6cf99862c2c692022-12-22T02:08:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.871216871216Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS AdministrationGustavo dos Santos Rosa0André Massahiro Teramoto Krieck1Enrico Topan Padula2Fernanda de Castro Stievani3Mariana Correa Rossi4João Pedro Hübbe Pfeifer5Roberta Martins Basso6Aline Márcia Marques Braz7Márjorie de Assis Golim8Márjorie de Assis Golim9Ana Liz Garcia Alves10Department of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilFlow Cytometry Laboratory, Applied Biotechnology Laboratory, Clinical Hospital of Botucatu Medical School, Botucatu, BrazilFlow Cytometry Laboratory, Applied Biotechnology Laboratory, Clinical Hospital of Botucatu Medical School, Botucatu, BrazilGraduate Program in Research and Development (Medical Biotechnology), Botucatu Medical School, São Paulo State University (UNESP), Botucatu, BrazilDepartment of Veterinary Surgery and Animal Reproduction, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, BrazilAllogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients’ sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections.https://www.frontiersin.org/articles/10.3389/fimmu.2022.871216/fullhumoral immune responsemesenchymal stromal cellsMHCintraarticular injectionmicrocytotoxicitycell rejection reactions |
| spellingShingle | Gustavo dos Santos Rosa André Massahiro Teramoto Krieck Enrico Topan Padula Fernanda de Castro Stievani Mariana Correa Rossi João Pedro Hübbe Pfeifer Roberta Martins Basso Aline Márcia Marques Braz Márjorie de Assis Golim Márjorie de Assis Golim Ana Liz Garcia Alves Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration Frontiers in Immunology humoral immune response mesenchymal stromal cells MHC intraarticular injection microcytotoxicity cell rejection reactions |
| title | Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration |
| title_full | Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration |
| title_fullStr | Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration |
| title_full_unstemmed | Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration |
| title_short | Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration |
| title_sort | production of cytotoxic antibodies after intra articular injection of allogeneic synovial membrane mesenchymal stem cells with and without lps administration |
| topic | humoral immune response mesenchymal stromal cells MHC intraarticular injection microcytotoxicity cell rejection reactions |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.871216/full |
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