Liver regeneration is of major clinical importance in the setting of liver injury, resection, and transplantation. A20, a potent anti-inflammatory and NF-κB inhibitory protein, has established pro-proliferative properties in hepatocytes, in part through decreasing expression of the Cyclin Dependent Kinase Inhibitor, p21. Both C-terminal (7-Zinc fingers; 7Zn) and N-terminal (Nter) domains of A20 were required to decrease p21 and inhibit NF-κB. However, both independently increased hepatocyte proliferation, suggesting that additional mechanisms contributed to the pro-proliferative function of A20 in hepatocytes. We ascribed one of A20’s pro-proliferative mechanisms to increased and sustained IL-6 induced STAT3 phosphorylation, as a result of decreased hepatocyte expression of the negative regulator of IL-6 signaling, SOCS3. This novel A20 function segregates with its 7Zn not Nter domain. Conversely, total and partial loss of A20 in hepatocytes increased SOCS3 expression, hampering IL-6-induced STAT3 phosphorylation. Following liver resection in mice pro-proliferative targets downstream of IL-6/STAT3 signaling were increased by A20 overexpression and decreased by A20 knockdown. In contrast, IL-6/STAT3 pro-inflammatory targets were increased in A20 deficient livers, and decreased or unchanged in A20 overexpressing livers. Upstream of SOCS3, levels of its microRNA regulator miR203 were significantly decreased in A20-deficient livers. Altogether these results demonstrate that A20 enhances IL-6/STAT3 pro-proliferative signals in hepatocytes by down-regulating SOCS3, likely through a miR203-dependent manner. This finding together with A20 reducing the levels of the potent cell cycle brake p21 establishes its pro-proliferative properties in hepatocytes and prompts the pursuit of A20-based therapies to promote liver regeneration and repair.

The human dental follicle is a developmental precursor for essential periodontal tissues such as periodontal ligament and root development. These cells can be expected to differentiate into several lineages, since they are derived from mesoderm. Especially the differentiation towards the osteogenic lineage could be interesting for tissue regeneration with or without growing on scaffold biomaterials in autologous transplantation for reconstruction of large bone defects and incorporation of teeth implants.Here we demonstrate a fast and efficient method to isolate stem cells out of the dental follicle of wisdom teeth and their more determined lineage specific commitment into the osteogenic direction.Typical markers confirmed the stem cell character of the isolated and differentiated cells and the successful differentiation has been verified in addition after lineage specific induction using corresponding stainings. In order to evaluate the quality of the cells microbiological investigations were performed and showed that all samples contained microbial species. Pre-treatment of patients with antibiotics reduced the number of microorganisms to a minimum but did not suffice to eliminate all bacteria. The predominantly found species were gram-positive cocci being either catalase-positive and oxidase-negative or catalase-and oxidase-negative. Most microorganisms belonged to the families of Streptococcaceae and Staphylococcaceae. During cultivation of the stem cells, the contamination with microorganisms could be easily suppressed by usage of standard cell culture conditions with penicillin and streptomycin.Key words: stem cell, dental follicle, osteogenic lineage, biomaterials, differentiation