Disclosures: The following people have nothing to disclose: Abdelrahman Zekri, Hosny M. Salama, Abeer Bahnassy, Shereen M. Al Alim, Ola Ahmed, Mai Lotfy, Eman Medhat, Rasha Ahmed, Sherief Musa Mesenchymal stem cells (MSC) display a striking immunoregulatory property. This property has been used in several clinical settings; particularly, MSC infusion could resolve severe, acute graft-vs-host disease. Apoptosis Compound Library Most of the data
suggest that this property involves secretion of specific cytokines and mechanisms mediated by cell-cell contact. In addition, MSC are also likely to modulate the differentiation and function of dendritic cells (DC). However, the underlying mechanisms are still poorly understood. In this study, we found that human MSC from umbilical cord (huc-MSC) induced immature dendritic cells (iDC) to differentiate into
a novel tolerogenic DC subset (MSC-DC) with a stable phenotype and function when cocultured. MSC-DC display the low immunogenicity and immune tolerance by triggering a T helper type 2-polarizing program and down-regulating the pro-inflammatory factor production. Further study demonstrates that huc-MSC induce the tolerogenic MSC-DC generation through the IL-6/STAT3/SOCS1/TLR4 signaling network. Huc-MSC induced the higher expression of SOCS1 in MSC-DC, which were activated by secreting a larger number of IL-6 through the JAK-STAT pathway, repressing toll like receptor 4 (TLR4) Ku-0059436 purchase signaling pathway, and ultimately inducing the generation of novel tolerogenic dendritic cells. Moreover, Huc-MSC could increase phophorylation of Akt, but inhibit phophorylation of IRF3. We also observed that amount of microRNAs changed when cocultured. We found that miR-378 was an important factor in the generation of novel tolerogenic
dendritic cells by targeting STAM2. These results indicate that microRNAs could play essential roles in the production of the tolerogenic MSC-DC. Taken together, our data proposed a new 上海皓元医药股份有限公司 molecular mechanism of MSC in regulating tolerogenic DC production and promote the clinical application of MSC in new and broader immune applications, including treatment of allograft rejection and graft-vs-host disease in organ transplantation and autoimmune liver diseases. Disclosures: The following people have nothing to disclose: Guo-Ying Wang, Yi-nan Deng, Yong Zou, Minru Li, Qi Zhang, Gui-Hua Chen Bioengineering of a fully functional tissue reguires precise recapitulate normal tissue development. Specifically for the liver, one may use bipotent human liver progenitor cells (hFLCs) capable of differentiation into hepatocytes and cholangiocytes.