Co-transplantation of pre-activated mesenchymal stem cells improves intraportal engraftment of islets by inhibiting liver natural killer cells in mice.

The activation of natural killer (NK) cells in the liver inhibits engraftment of intraportally transplanted islets. We attempted to modulate the activity of NK cells by co-transplanting mesenchymal stem cells (MSCs) with islets in mice. We first investigated the ability of MSCs to secrete prostaglandin E2 (PGE2), a predominant inhibitor of NK cell function, in various combinations of inflammatory cytokines. Notably, we found that PGE2 production was partially delayed in MSCs activated by inflammatory cytokines in vitro, whereas liver NK cells were activated early after islet transplantation in vivo. Accordingly, pre-activated MSCs, but not naive MSCs, substantially suppressed the expression of activation markers in liver NK cells after co-transplantation with islets. Similarly, co-transplantation with pre-activated MSCs, but not naive MSCs, markedly improved the survival of islet grafts. These results highlight MSC co-transplantation as an effective and clinically feasible method for enhancing engraftment efficiency. This article is protected by copyright. All rights reserved.