Myeloma bone disease (MBD) is the most visible aspect of plasma cell myeloma (PCM), which is characterized by the displacement of hematopoiesis and the formation of osteolytic bone lesions. The secreted glycoprotein Dickkopf-1 (DKK1), an inhibitor of the Wnt signaling pathway, is broadly expressed in myeloma cells but highly restricted in normal tissues. DKK1 plays a critical role in several aspects of bone biology and actively participates in regulating MBD by inhibiting osteoblasts and by activating osteoclasts. Based on these findings, ongoing research has been targeting DKK1 to find novel therapeutic strategies for MBD, such as DKK1-neutralizing antibodies, proteasome inhibitors, and vaccines. All these strategies have produced encouraging clinical results and consequently, revealed the significance of DKK1 in MBD. This review discusses the recent advances in our understanding of the DKK1 pathway signaling and how DKK1 can be exploited in the therapeutic intervention of MBD.

It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets. In vitro, islet function was measured by a glucose-stimulated insulin secretion test; cytokines in cultured supernatants were assessed by enzyme-linked immunosorbent assay; and gene expression was analyzed by reverse transcription-quantitative PCR. In vivo, islet transplantation was performed in rats, and graft function and survival were monitored by measuring the blood glucose levels. In vitro, the SIS-MSC scaffold was associated with improved islet viability and enhanced insulin secretion compared with the controls, as well as with the increased the expression of insulin 1 (Ins1), pancreatic and duodenal homeobox 1 (Pdx1), platelet endothelial cell adhesion molecule 1 [Pecam1; also known as cluster of differentiation 31 (CD31)] and vascular endothelial growth factor A (Vegfa) in the islets, increased growth factor secretion, and decreased tumor necrosis factor (TNF) secretion. In vivo, the SIS-MSC scaffold was associated with improved islet function and graft survival compared with the SIS and control groups. On the whole, our findings demonstrate that the SIS-MSC scaffold significantly improved pancreatic islet function and survival in vitro and in vivo. This improvement may be associated with the upregulation of insulin expression, the improvement of islet microcirculation and the secretion of cytokines.

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Infusion of Sertoli cells could effectively prolong the survival of islet grafts and reduce peripheral blood lymphocyte and cytokine levels. In this process, transforming growth factor-beta1 played a major role and Fas ligand played a smaller additional role.