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International Journal of Bioprinting                               Liver printing: from structure to application




            Table 1. Types of cells in the liver 35
             Cell types      Amount               Characteristics and functions             Markers
             Hepatocytes     Approximately 60% of total   Highly polarized epithelial cells that form cord-like structures;   ALB, HNF4α, CK18,
                             liver cells; approximately 80%  gluconeogenesis, β-oxidation, drug metabolism, and   CYP3A4
                             of liver volume      detoxification
             Liver sinusoidal   Approximately 15–20% of   Form a dynamic barrier between blood and the hepatic   CD31, LYVE1, CD34,
             endothelial cells 36–38  liver cells; 3% of liver volume   microenvironment; scavenger endothelial cells, i.e., clear large   CD105  39
                                                  molecules from the blood via receptor-mediated endocytosis
                                                  through fenestrations
             Cholangiocytes 40–43   3–5% of total human liver   Secrete bile into the duodenum; hormone-mediated   SOX9, CK7, CK19,
             (biliary epithelial cells)  cells    regulation of bile flow and alkalinity; absorb bile acids and   CFTR, SLC4A2 44
                                                  reabsorb bile components, such as glucose and glutathione;
                                                  contribute approximately 40% of total bile production via
                                                  ion transporters and hormone receptors on their polarized
                                                  membranes; synthesize and secrete various pro-inflammatory
                                                  factors, cytokines, chemokines, and angiogenic factors; actively
                                                  participate in inflammatory responses
             Hepatic stellate cells 45,46  5–8% of total liver cells  Primary reservoir of vitamin A; major contributor to tissue   α-SMA, RBP1
                                                  fibrosis; express α-smooth muscle actin (ACTA2) upon
                                                  activation for extracellular matrix deposition
             Kupffer cells 47,48  2% of liver volume  Immune sentinels in the liver; identification and clearance   CD68, MARCO
                                                  of foreign substances; secretion of cell factors (e.g., TGF and
                                                  TNF); involvement in the metabolism of bilirubin, iron,
                                                  lipoproteins, and cholesterol
             Lymphocytes (T cells,   NK cells: 20–30% of the total   NK and T cells serve as the first-line immune defense against   CD4, CD8, KLRC1,
             natural killer [NK]-like  lymphocyte population in   invading pathogens, modulate liver injury, and recruit   NCR1
             cells, B cells)  the liver; B cells: 37.5% of   circulating lymphocytes; B cells affect immune control directly
                             the intrahepatic immune cell   via neutralizing antibodies, or indirectly via communication
                             population           with the complement cascade and other effector immune cells

            Table 2. Developmental stages and corresponding characteristics in the liver 52

             Developmental stage  Characteristics
             E7.5 (W3)            Separation of the definitive endoderm from the mesoderm, eventually developing into foregut, midgut, and hindgut
             E8.0                 Establishment of the STM
             E8.5 (W3–4)          Emergence of hepatic progenitor cells in the ventral foregut endoderm
             E9.0 (W4)            Formation of hepatic diverticulum and hepatic bud
             E10.5–12.5 (W4–6)    Development of the portal vein and central vein
             E11.5                Onset of extensive hematopoietic cell proliferation
             E11.5 (W6)           Morphological transformation of hepatic bud into distinct liver tissue; formation of the bile duct plate
             E13.5–15.5           Differentiation of hepatoblasts into hepatocytes
             E15.0 (W12)          Formation of asymmetric primitive bile duct structures, subsequently transforming into symmetric bile duct
                                  structures
             Perinatal period (W8)   Emergence of the hepatic artery
             Postnatal            Liver weight increases by at least 500%; establishment of lobular pattern
            Abbreviations: E, mouse embryonic day; STM, septum transversum mesenchyme; W, human week.


            quickly and pose fewer ethical concerns when used for   Recently, Wei and Sun’s team pioneered gene-edited
            organ transplantation, making them the primary animal   pig liver xenotransplantation by transplanting the liver of a
            source for xenotransplantation research. With gene editing   pig with 10 genetic modifications into a 71-year-old male
            technology, successful live pig heart and kidney transplants   patient with a large right lobe liver cancer. This procedure
            have already been achieved. 61,62                  included the knockout of three pig xenogeneic antigen


            Volume 10 Issue 5 (2024)                       124                                doi: 10.36922/ijb.3819
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