Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+ T-cell suppression.
Mesenchymal stromal stem cells (MSCs) are an attractive therapeutic model for regenerative medicine due to their pluripotency. MSCs are used as a treatment for several inflammatory diseases, including hepatitis. However, the detailed immunopathological impact of MSC treatment on liver disease, particularly for adipose tissue derived stromal stem cells (ADSCs), has not been described. Here, we investigated the immuno-modulatory effect of ADSCs on hepatitis using an acute ConA C57BL/6 murine hepatitis model. i.v. administration of ADSCs simultaneously or 3 h post injection prevented and treated ConA-induced hepatitis. Immunohistochemical analysis revealed higher numbers of CD11b(+), Gr-1(+), and F4/80(+) cells in the liver of ConA-induced hepatitis mice was ameliorated after the administration of ADSCs. Hepatic expression of genes affected by ADSC administration indicated tissue regeneration-related biological processes, affecting myeloid-lineage immune-mediating Gr-1(+) and CD11b(+) cells. Pathway analysis of the genes expressed in ADSC-treated hepatic inflammatory cells revealed the possible involvement of T cells and macrophages. TNF-α and IFN-γ expression was downregulated in hepatic CD4(+) T cells isolated from hepatitis livers co-cultured with ADSCs. Thus, the immunosuppressive effect of ADSCs in a C57BL/6 murine ConA hepatitis model was dependent primarily on the suppression of myeloid-lineage cells and, in part, of CD4(+) T cells.
Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan.
Mami
M
Higashimoto
Yoshio
Y
Sakai
Masayuki
M
Takamura
Soichiro
S
Usui
Alessandro
A
Nasti
Keiko
K
Yoshida
Akihiro
A
Seki
Takuya
T
Komura
Masao
M
Honda
Takashi
T
Wada
Kengo
K
Furuichi
Takahiro
T
Ochiya
Shuichi
S
Kaneko
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D003208:Concanavalin A; D015536:Down-Regulation; D005260:Female; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000943:Antigens, Differentiation; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C036763:monocyte-macrophage differentiation antigen; D003208:Concanavalin A; D007371:Interferon-gamma
Adipose tissue derived stromal stem cells; Anti-inflammatory effects; CD4+ T cells; ConA hepatitis; Myeloid-lineage cells