Here, we engineered a micropatterned
co-culture (iMPCC) platform in a multi-well format that, in contrast to conventional confluent cultures, significantly enhanced the functional maturation and longevity of iHeps in culture for at least 4 weeks in vitro when benchmarked selleck chemicals against multiple donors of PHHs. In particular, iHeps were micropatterned onto collagen-coated domains of empirically optimized dimensions, surrounded by 3T3-J2 murine embryonic fibroblasts, and then sandwiched with a thin layer of ECM gel (Matrigel™). We assessed iHep maturity via global gene expression profiles, hepatic polarity, secretion of albumin and urea, basal CYP450 activities, phase-II conjugation, drug-mediated CYP450 induction, and drug-induced hepatotoxicity. Conclusion: Controlling both homotypic interactions between iHeps and heterotypic interactions with stromal fibroblasts significantly
matures iHep functions and maintains them for several weeks in culture. In the future, iMPCCs could prove useful for drug screening, studying molecular mechanisms underlying iHep differentiation, modeling liver diseases, and integration into human-on-a-chip systems being designed to assess multi-organ responses to compounds. This article is protected by copyright. All rights reserved. “
“It has been suggested that there could be three possible mechanisms of gastric dysfunction in patients with FD: (i) delayed gastric Selleckchem Romidepsin emptying, (ii) impaired gastric accommodation of food intake, and (iii) hypersensitivity to gastric distention. Postprandial fullness seems to be the most severe symptom in patients who report aggravation of their symptoms after meals. Therefore, see more it has been assumed that delayed gastric emptying and consequent prolonged antral distension could reduce hunger, increase satiety, and even cause gastric discomfort, all of which would pose a significant barrier to adequate nutrition. We previously reported that postprandial water intake inhibits gastric antral motility along with an increase of cholecystokinin (CCK) in normal subjects. We assumed that the rapid increase of CCK after water
intake was initiated by a feedback mechanism related to the inflow of fatty chyme into the duodenum that inhibits gastric antral activity. This duodeno-gastric interaction is known as the “duodenal break.” We also reported that total gastric emptying was more rapid after the intake of a high-viscosity liquid meal than after a low-viscosity meal, because the low-viscosity liquid meal inhibits gastric empting after rapid initial inflow into the duodenum. Considering these results, we hypothesized that rapid gastric emptying, rather than delayed gastric emptying, could be a cause of FD. In some patients with postprandial distress syndrome (PDS), we have found a significant correspondence between PDS-related dyspepsia and accelerated gastric emptying in the early postprandial period.