Human Liver Sinusoid on a Chip for Hepatitis B Virus Replication Study
Autor: | Moses Noh, Nicholas Duchemin, Young Bok Abraham Kang, Siddhartha Rawat, Michael J. Bouchard |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
lcsh:Mechanical engineering and machinery liver sinusoid medicine.disease_cause HBV replication study Article 03 medical and health sciences 0302 clinical medicine Sinusoid human-liver-sinusoid-on-a-chip Antigen Cell surface receptor Hepatitis B virus (HBV) hepatocyte microfluidic platform medicine lcsh:TJ1-1570 Electrical and Electronic Engineering Hepatitis B virus Liver sinusoid Hepatocyte differentiation Chemistry Mechanical Engineering virus diseases Molecular biology digestive system diseases 3. Good health HBcAg 030104 developmental biology medicine.anatomical_structure Control and Systems Engineering Hepatocyte 030211 gastroenterology & hepatology |
Zdroj: | Micromachines, Vol 8, Iss 1, p 27 (2017) Micromachines Micromachines; Volume 8; Issue 1; Pages: 27 |
Popis: | We have developed a miniature human liver (liver-sinusoid-on-a-chip) model using a dual microchannel separated by a porous membrane. Primary human hepatocytes and immortalized bovine aortic endothelial cells were co-cultured on opposite sides of a microporous membrane in a dual microchannel with continuous perfusion. Primary human hepatocytes in this system retained their polygonal morphology for up to 26 days, while hepatocytes cultured in the absence of bovine aortic endothelial cells lost their morphology within a week. In order to demonstrate the utility of our human-liver-sinusoid-on-a-chip, human hepatocytes in this system were directly infected by Hepatitis B Virus (HBV). Expression of the HBV core antigen was detected in human hepatocytes in the microchannel system. HBV replication, measured by the presence of cell-secreted HBV DNA, was also detected. Importantly, HBV is hepatotropic, and expression of HBV RNA transcripts is dependent upon expression of hepatocyte-specific factors. Moreover, HBV infection requires expression of the human-hepatocyte-specific HBV cell surface receptor. Therefore, the ability to detect HBV replication and Hepatitis B core Antigen (HBcAg) expression in our microfluidic platform confirmed that hepatocyte differentiation and functions were retained throughout the time course of our studies. We believe that our human-liver-sinusoid-on-a-chip could have many applications in liver-related research and drug development. |
Databáze: | OpenAIRE |
Externí odkaz: |