期刊
CELL TRANSPLANTATION
卷 24, 期 8, 页码 1585-1598出版社
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096368914X682819
关键词
Human pancreatic duct cell; Islet transplantation; Immunosuppressant; Cytoldnes; Angiogenesis; Dedifferentiation
资金
- KU LEUVEN [GOA 2009/10]
- Belgian government (Interuniversity Attraction Poles, program P6/40 of the Belgian Federal Science Policy Office)
- European Community [241883, 241447]
- Juvenile Diabetes Research Foundation [4-2005-1327]
- IRO fellowship of the KU LEUVEN
The presence of pancreatic duct cells in clinical islet grafts may affect long-term metabolic success. Human pancreatic duct cells express factors that may exert both protective and damaging effects on islet cells in the graft. Here we studied the potential of commonly used immunosuppressive drugs in islet transplantation sirolimus, tacrolimus, and mycophenolate mofetil (MMF) to influence the inflammatory and angiogenic capacity of human pancreatic duct cells in addition to their proliferation and reprogramming abilities. Our data show that the expression of specific proinflammatory cytoldnes by the human pancreatic duct cells was either unaltered or inhibited by the immunosuppressants studied, especially tacrolimus and MMF, whereas expression of chemotactic and angiogenic factors was unaffected. Although none of the immunosuppressants directly led to duct cell death, MMF prevented duct cell proliferation, and sirolimus inhibited neurogenin 3-mediated duct-to-(neuro)endocrine cell reprogramming. Our data indicate that the immunosuppressant tacrolimus was the least aggressive on the angiogenic, proliferative, and reprogramming potential of human pancreatic duct cells, while it was most powerful in inhibiting inflammatory cytokines, which may influence the outcome of islet transplantation.
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