PD-L1 overexpression conveys tolerance of mesenchymal stem cell-derived cardiomyocyte-like cells in an allogeneic mouse model
| Autor: | Reza Rahbarghazi, Alireza Mardomi, Nabiallah Mohammadi, Saeid Abediankenari, Bahareh Hasani, Shabanali K. Limoni, Hossein Ranjbaran, Narjes Jafari, Hadi Hossein Nataj, Mohsen Khorashadizadeh |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology T cell T-Lymphocytes Clinical Biochemistry Lymphocyte proliferation Lymphocyte Activation B7-H1 Antigen 03 medical and health sciences Interferon-gamma 0302 clinical medicine medicine Immune Tolerance Animals Transplantation Homologous Myocytes Cardiac Mice Inbred BALB C Chemistry Alloimmunity Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology Cell biology Interleukin-10 Transplantation Mice Inbred C57BL Tolerance induction Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Female CD80 CD8 Spleen |
| Zdroj: | Journal of cellular physiologyREFERENCES. 236(9) |
| ISSN: | 1097-4652 |
| Popis: | Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4+ and CD8+ T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8+ T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4+ and CD8+ T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction. |
| Databáze: | OpenAIRE |
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