Effect of allogeneic bone marrow-derived mesenchymal stem cells transplantation in a polyI:C-induced primary biliary cirrhosis mouse model.
Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune disease of unknown mechanism. We established a PBC animal model by injecting C57BL/6 mice with polyinosinic-polycytidylic acid sodium (polyI:C) to investigate the therapeutic effect of bone marrow-derived mesenchymal stem cells (BM-MSC) on this model. After 6 weeks of MSC infusion, serum aminotransferase and autoimmune antibodies declined, and histological examination by hematoxylin and eosin staining showed significant amelioration of monocytes infiltration around bile ducts of mice treated with BM-MSC. Interestingly, allogeneic BM-MSC transplantation markedly increased CD4(+)Foxp3(+) regulatory T cells in peripheral blood as well as in lymph nodes when analyzed by flow cytometry. Further examination showed serum TGF-β1 increased but IFN-γ decreased significantly in PBC mice treated with MSC, while with no obvious change in IL-10 expression. Our results for the first time suggested that BM-MSC transplantation could regulate systemic immune response and enhance recovery in liver inflammation of PBC mice, raising the possibility for clinical application of allogeneic MSC in treatment of early-stage PBC patients.
Wang
Dandan
D
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, 210008 Nanjing, Jiangsu, China.
Zhang
Huayong
H
Liang
Jun
J
Gu
Zhifeng
Z
Ma
Xiaolei
X
Huang
Jing
J
Lin
Jing
J
Hou
Yayi
Y
Lu
Liwei
L
Sun
Lingyun
L
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D006651:Histocytochemistry; D016753:Interleukin-10 / Q000096:biosynthesis; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000139:chemically induced* / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000633:toxicity*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology; D000637:Transaminases / Q000097:blood; D014184:Transplantation, Homologous
D001323:Autoantibodies; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10; D000637:Transaminases; D011070:Poly I-C