TY - JOUR
T1 - Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation
AU - Wen, Di
AU - Peng, Yang
AU - Liu, Di
AU - Weizmann, Yossi
AU - Mahato, Ram I.
N1 - Funding Information:
We would like to thank Otis Foundation , Nebraska Research Initiative (NRI) and University of Nebraska Medical Center Faculty start up fund for financial support. Parts of this study were presented in abstract form at the 2015 American Association of Pharmaceutical Sciences Annual Meeting, Orlando, FL, 25–29 October 2015 and 2013 American Association of Pharmaceutical Sciences Annual Meeting, San Antonio, TX, 10–14 November 2013.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/9/28
Y1 - 2016/9/28
N2 - Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation.
AB - Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation.
KW - Exosome
KW - Immunotherapy
KW - Islet transplantation
KW - Type 1 diabetes
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U2 - 10.1016/j.jconrel.2016.07.044
DO - 10.1016/j.jconrel.2016.07.044
M3 - Article
C2 - 27475298
AN - SCOPUS:84979989085
VL - 238
SP - 166
EP - 175
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -