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Development of a pancreas-liver organ-on-chip coculture model for organ-to-organ interaction studies
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International audience. Advances in organ-on-chip technology allowed the recapitulation of two or more organs interaction thanks to dedicated microbioreactors interconnected by microfluidic network. Here, we developed pancreas-liver coculture model in a microfluidic biochip, using rat Langerhans islets and hepatocytes. The behavior and functionality of the model were compared to islets and hepatocytes (with/without insulin) monocultures. We confirmed the insulin, glucagon and C-peptide secretions by islets monoculture and coculture. Furthermore, C-peptide and insulin secretions were higher in coculture after 5 days of culture. The islets coculture presented downregulation of Pdx1, Glut2, Gcg, App, Ins1, Neurod, Neurog3 and Gcgr genes, compared to monocultures. In hepatic compartment, the monocultures without insulin were negative to CK18 staining and displayed a weaker production of albumin when compared to monocultures with insulin. They also presented a moderate protein expression of CYP3A2, GLUT2, INSR and modulation of several hepatic genes. In coculture model, hepatocytes displayed albumin productions similar to those in monoculture with insulin. The hepatocytes cocultures were highly positive to INSR, GLUT2, CK18 and CYP3A2 immunostaining and allowed to recover mRNA levels similar to monoculture with insulin (Gcgr, Insr, Hnf4a, Igfbp1 and Alb). The result illustrated that islets can produce insulin to supplement the culture medium and recover hepatic functionality. We believe that our model illustrated the potential of organ-on-chip technology to reproduce cross-talk between liver and pancreas.
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