Journal
CELL STEM CELL
Volume 16, Issue 2, Pages 148-157Publisher
CELL PRESS
DOI: 10.1016/j.stem.2014.12.001
Keywords
-
Categories
Funding
- CIRM [RM1-01703, DR1-01423]
Ask authors/readers for more resources
Type 1 diabetes (T1D) is an autoimmune disease caused by T cell-mediated destruction of insulin-producing beta cells in the islets of Langerhans. In most cases, reversal of disease would require strategies combining islet cell replacement with immunotherapy that are currently available only for the most severely affected patients. Here, we demonstrate that immunotherapies that target T cell costimulatory pathways block the rejection of xenogeneic human embryonic-stem-cell-derived pancreatic endoderm (hESC-PE) in mice. The therapy allowed for long-term development of hESC-PE into islet-like structures capable of producing human insulin and maintaining normoglycemia. Moreover, short-term costimulation blockade led to robust immune tolerance that could be transferred independently of regulatory T cells. Importantly, costimulation blockade prevented the rejection of allogeneic hESC-PE by human PBMCs in a humanized model in vivo. These results support the clinical development of hESC-derived therapy, combined with tolerogenic treatments, as a sustainable alternative strategy for patients with T1D.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available