Basic–Liver, Pancreas, and Biliary TractPlatelet-Derived Growth Factor Signaling Through Ephrin-B2 Regulates Hepatic Vascular Structure and Function
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Cell Culture
All tissue culture and transfection reagents were obtained from GIBCO (Rockville, MD). Isolated primary human HSC and primary human SEC (ScienCell Research Laboratories, Carlsbad, CA) were used between passages 2 and 6. Their phenotypic characterization has been previously described.7, 8 HSC and SEC were cultured in defined medium (ScienCell) and supplemented with 10% fetal bovine serum (where indicated), L-glutamine (1 mmol/L), penicillin (100 IU/mL), and streptomycin (100 μg/mL). In some
PDGF Promotes an Angiogenic Phenotype of HSC That Facilitates Vascular Tube Formation
In liver, HSC are best characterized by their capacity to deposit collagen matrix; other traditional functions frequently ascribed to pericytes in other organ beds are less defined in the context of HSC, including interaction with endothelial cells (EC) to form angiogenic vascular networks. To explore this concept, human HSC and human SEC were labeled with complementary vital dyes and then cocultured on Matrigel. Coculture of HSC and EC (ratio, 1:3) on Matrigel leads to formation of a vascular
Discussion
Whereas pressure regulation within the sinusoids is highly dependent on vasoregulatory mediators, the ability of the sinusoids to contract requires the generation of a critical mass of HSC that align themselves in an effective manner around the vessel lumen. This process, which we refer to as pathologic sinusoidal remodeling, requires the recruitment of “angiogenic” HSC to the vessel wall or activation of local HSC with extension of tentacle-like structures from these cells that encircle the
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D.S. and A.D. contributed equally to this work.
Conflicts of interest: The contributors disclose no conflicts of interest.