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Bone marrow derived mesenchymal stem cells (BM-MSC) is a promising alternative cell source to primary hepatocytes because of their ability to differentiate into hepatocyte-like cells. However, their inability to differentiate efficiently and potential to turn into myofibroblasts restrict their applications. This study developed a plate coating from the liver extracellular matrix (ECM) and investigated its ability in facilitating the BM-MSCs proliferation, hepatic differentiation, and hepatocyte-specific functions during in vitro culture. After 28-day culture, BM-MSCs on the ECM coating showed hepatocyte-like morphology, and certain cells took up low-density lipoprotein. Synthesis of albumin, urea, and anti-alpha-fetoprotein, as well as expression of certain hepatic markers, in cells cultured on ECM were higher than cells cultured on non-coated and Matrigel-coated plates. mRNA levels of CYP3A4, albumin, CK18, and CYP7A1 in cells on ECM coating were significantly higher than cells cultured on the non-coating environment. In conclusion, viability and hepatogenic differentiation of BM-MSCs cultured on both Matrigel and ECM coating were significantly enhanced compared with those cultured on non-coated plates. Moreover, the liver ECM coating induced additional metabolic functions relative to the Matrigel coating. The liver ECM hydrogel preserves the natural composition, promotes simple gelling, induces efficient stem cell hepatogenic differentiation, and may have uses as an injectable intermedium for hepatocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 829-838, 2018.

Social behaviors of most mammals are profoundly affected by chemical signals, pheromones, exchanged between conspecifics. Pheromones interact with dendritic microvilli of bipolar neurons in the vomeronasal organ (VNO). To investigate vomeronasal signal transduction pathways, microvillar membranes from porcine VNO were prepared. Incubation of such membranes from prepubertal females with boar seminal fluid or urine results in an increase in production of inositol-(1, 4, 5)-trisphosphate (IP3). The dose response for IP3 production is biphasic with a GTP-dependent component at low stimulus concentrations and a nonspecific increase in IP3 at higher stimulus concentrations. The GTP-dependent stimulation is mimicked by GTPgammaS and blocked by GDPbetaS. Furthermore, the GTP-dependent component of the stimulation of IP3 production is sex specific and tissue dependent. Studies with monospecific antibodies reveal a G alpha(q/11)-related protein in vomeronasal neurons, concentrated at their microvilli. Our observations indicate that pheromones in boar secretions act on vomeronasal neurons in the female VNO via a receptor mediated, G protein-dependent increase in IP3. These observations set the stage for further investigations on the regulation of stimulus-excitation coupling in vomeronasal neurons. The pheromone-induced IP3 response also provides an assay for future purification of mammalian reproductive pheromones.

SUMMARY The vomeronasal organ (VNO) has evolved to link an animal's behavior to its environment in a highly species-specific fashion. In mice, it is thought to be the primary sensory system responsible for the detection of pheromones. Pheromones regulate a variety of responses including mate recognition in the context of selective pregnancy failure. MHC (major histocompatibility complex)class I peptides have been identified as compounds that elicit the pregnancy block effect via the VNO. However, the transduction cascade of these molecules is unknown and it is not known if the production of these compounds are androgen dependent. By using male urine and MHC peptides, we show that female mice treated with MHC peptides (in urine or PBS) and urine from castrated males or juvenile mice of different haplotypes respond to the Bruce Effect paradigm in a manner equivalent to female mice exposed to whole urine. In addition to providing new evidence that urine from castrated or juvenile males and MHC peptides can induce pregnancy block, we show correlation of the effect with an increase in inositol 1,4,5-trisphosphate.