Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration

Autor(es)

Rosa, Gustavo Dos Santos ; Teramoto Krieck, Andre Massahiro ; Padula, Enrico Topan ; Stievani, Fernanda de Castro ; Rossi, Mariana Correa ; Hubbe Pfeifer, Joao Pedro ; Basso, Roberta Martins ; Marques Braz, Aline Marcia ; Golim, Marjorie de Assis ; Garcia Alves, Ana Liz

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 13, p. 12-pg., 2022-04-27.

Resumo

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. (AU)

• Processo FAPESP: 17/14460-4 - Efeito da administração intra-articular de microcápsulas com células tronco mesenquimais adultas no tratamento da osteoartrite
• Beneficiário: Ana Liz Garcia Alves
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/12815-0 - Dor e qualidade de vida em animais
• Beneficiário: Stelio Pacca Loureiro Luna
• Modalidade de apoio: Auxílio à Pesquisa - Temático