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Cotransplantation of preactivated mesenchymal stem cells improves intraportal engraftment of islets by inhibiting liver natural killer cells in mice
Author(s) -
Ishida Nobuki,
Ishiyama Kohei,
Saeki Yoshihiro,
Tanaka Yuka,
Ohdan Hideki
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15347
Subject(s) - mesenchymal stem cell , islet , medicine , immunology , in vivo , transplantation , cytokine , cancer research , biology , endocrinology , insulin , pathology , microbiology and biotechnology
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 cotransplanting mesenchymal stem cells ( MSC s) with islets in mice. We first investigated the ability of MSC s to secrete prostaglandin E2 , a predominant inhibitor of NK cell function, in various combinations of inflammatory cytokines. Notably, we found that prostaglandin E2 production was partially delayed in MSC s activated by inflammatory cytokines in vitro , whereas liver NK cells were activated early after islet transplant in vivo. Accordingly, preactivated MSC s, but not naive MSC s, substantially suppressed the expression of activation markers in liver NK cells after cotransplant with islets. Similarly, cotransplant with preactivated MSC s, but not naive MSC s, markedly improved the survival of islet grafts. These results highlight MSC cotransplant as an effective and clinically feasible method for enhancing engraftment efficiency.