Mian Long
Mian Long, PhD
professor
Institute of Mechanics, Chinese Academy of Sciences (CAS)
the Center for Biomechanics and Bioengineering
Beijing Key Laboratory of Engineered Construction and Mechanobiology
Email: mlong@imech.ac.cn
Biography:
Dr. Long is a professor at Institute of Mechanics, Chinese Academy of Sciences (CAS) and the directors of Center for Biomechanics and Bioengineering and of Beijing Key Laboratory of Engineered Construction and Mechanobiology. His interests are focused on molecular biomechanics, cellular mechanobiology, and tissue construction related to immune responses and liver diseases. He has published 142 peer-reviewed papers together with 11 warranted patents. He is awarded by National Outstanding Young Investigator Award from National Natural Science Foundation of China and by Young Teacher Award from Ministry of Education of China. Dr. Long is a fellow of American Institute of Medical and Biological Engineering and of International Academy of Medical and Biological Engineering.
Abstract:
Multiscale Mechanobiology and Engineered Construction in Liver Sinusoids
Liver sinusoid consists of multiple types of cells including liver sinusoid endothelial cells (LSECs), Kuppfer cells (KCs), hepatic stellate cells (HSCs), and hepatocytes (HCs), together with blood flow in main stream and interstitial flow in Disse gap. Reconstruction of liver sinusoids is critical for understanding the mechano-biological coupling between residing hepatic cells and flowing leukocytes or tumor cells, as well as for applying these modules in drug screening or bioartificial liver supporting system.
Here we developed an in vitro 3D model to recapitulate key features of liver sinusoids and to elucidate the roles of cellular interactions and shear flow in liver-specific PMN recruitment and LSEC fenestrae regulation. Two microfabricated polydimethylsiloxane (PDMS) layers were bonded together, forming two fluidic channels separated by a permeable polyethylene (PE) membrane to mimic a liver sinusoid with an endothelium separating microvenule and Disse Space. To replicate the physiological structure and cellular composition, LSEC monolayer with sparsely distributed KCs and HSCs was integrated on either side of extracellular matrix (ECM)-coated PE membrane and HC monolayer was immobilized in lower compartment. Typical liver specific functions and multi-typed cell interplay in protein secretion, drug metabolism and immune responses were analyzed. Data indicated that shear flow fostered albumin secretion for HCs alone or even higher when co-culturing with nonparenchymal cells, implying that co-culture and shear flow could work cooperatively. Shear flow enhanced dramatically CYP1A2 activity when HCs were cultured alone or co-cultured with NPCs. Co-culture of LSECs with respective HSCs, KCs, or HCs, or with all cell types increased PMN accumulation, implying that each type of hepatic cells may contribute to PMN recruitment differently. Thus, this 3D microfluidic device can replicate the key architecture of liver sinusoids by integrating four major types of cells into two separated flow channels, serving as a potential platform to investigate hepatic cellular interplay, cytotoxic metabolism, and inflammatory cascade under physiologically-like microenvironment.
professor
Institute of Mechanics, Chinese Academy of Sciences (CAS)
the Center for Biomechanics and Bioengineering
Beijing Key Laboratory of Engineered Construction and Mechanobiology
Email: mlong@imech.ac.cn
Biography:
Dr. Long is a professor at Institute of Mechanics, Chinese Academy of Sciences (CAS) and the directors of Center for Biomechanics and Bioengineering and of Beijing Key Laboratory of Engineered Construction and Mechanobiology. His interests are focused on molecular biomechanics, cellular mechanobiology, and tissue construction related to immune responses and liver diseases. He has published 142 peer-reviewed papers together with 11 warranted patents. He is awarded by National Outstanding Young Investigator Award from National Natural Science Foundation of China and by Young Teacher Award from Ministry of Education of China. Dr. Long is a fellow of American Institute of Medical and Biological Engineering and of International Academy of Medical and Biological Engineering.
Abstract:
Multiscale Mechanobiology and Engineered Construction in Liver Sinusoids
Liver sinusoid consists of multiple types of cells including liver sinusoid endothelial cells (LSECs), Kuppfer cells (KCs), hepatic stellate cells (HSCs), and hepatocytes (HCs), together with blood flow in main stream and interstitial flow in Disse gap. Reconstruction of liver sinusoids is critical for understanding the mechano-biological coupling between residing hepatic cells and flowing leukocytes or tumor cells, as well as for applying these modules in drug screening or bioartificial liver supporting system.
Here we developed an in vitro 3D model to recapitulate key features of liver sinusoids and to elucidate the roles of cellular interactions and shear flow in liver-specific PMN recruitment and LSEC fenestrae regulation. Two microfabricated polydimethylsiloxane (PDMS) layers were bonded together, forming two fluidic channels separated by a permeable polyethylene (PE) membrane to mimic a liver sinusoid with an endothelium separating microvenule and Disse Space. To replicate the physiological structure and cellular composition, LSEC monolayer with sparsely distributed KCs and HSCs was integrated on either side of extracellular matrix (ECM)-coated PE membrane and HC monolayer was immobilized in lower compartment. Typical liver specific functions and multi-typed cell interplay in protein secretion, drug metabolism and immune responses were analyzed. Data indicated that shear flow fostered albumin secretion for HCs alone or even higher when co-culturing with nonparenchymal cells, implying that co-culture and shear flow could work cooperatively. Shear flow enhanced dramatically CYP1A2 activity when HCs were cultured alone or co-cultured with NPCs. Co-culture of LSECs with respective HSCs, KCs, or HCs, or with all cell types increased PMN accumulation, implying that each type of hepatic cells may contribute to PMN recruitment differently. Thus, this 3D microfluidic device can replicate the key architecture of liver sinusoids by integrating four major types of cells into two separated flow channels, serving as a potential platform to investigate hepatic cellular interplay, cytotoxic metabolism, and inflammatory cascade under physiologically-like microenvironment.