Although mesenchymal stromal cells (MSCs) show great potential for use in regenerative medicine, their therapeutic efficacy remains limited because of their low adaptation efficiency and viability observed in clinical trials. To potentiate the adaptation and survival efficiency of MSCs after administration in vivo, silk fibroin nanofibers (SFNs) were applied as a scaffold. SFNs are biocompatible, biodegradable polymers with tunable architectures and mechanical properties. Treatment with interferon (IFN)-gamma for 18 h increased the expression of immunomodulatory functional cytokines, IDO and COX2 in MSCs. Further, the MSCs grown on SFN sheets showed enhanced IDO1 and COX2 expression following IFN-gamma treatment. MSCs showed significantly greater migratory ability on SFN sheets than on glass surfaces or PLGA control sheets. Though IFN-gamma treatment slightly reduced the migration ability of MSCs cultured on glass or poly(lactic-co-glycolic acid) (PLGA) nanofiber sheets, it did not alter MSC motility on SFN sheets. Furthermore, MSCs cultured on SFN sheets dramatically suppressed TNF-alpha secretion from lipopolysaccharide-activated murine splenocytes, suggesting that the immunomodulatory function of MSCs was enhanced by the SFN sheets. Taken together, these data demonstrate that SFN sheets potentiate the reparative and regenerative properties of MSCs. (C) 2019 The Authors. Published by Elsevier Inc.