TY - JOUR
T1 - Endothelium-mediated hepatocyte recruitment in the establishment of liver-like tissue in vitro
AU - Nahmias, Yaakov
AU - Schwartz, Robert E.
AU - Hu, Wei Shou
AU - Verfaillie, Catherine M.
AU - Odde, David J.
PY - 2006/6
Y1 - 2006/6
N2 - A major goal of liver tissue engineering is to understand how the constituent cell types interact to achieve liver-specific structure and function. Here we show that hepatocytes migrate toward and adhere to endothelial vascular structures formed on Matrigel in vitro, and that hepatocyte recruitment is dependent on endothelium-derived hepatocyte growth factor. The hepatocyte-decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and a lumen. The sinusoid-like structures retained cytochrome P450 expression and activity, in addition to stable albumin expression and secretion rate for over 2 months in vitro. The stability of the sinusoid-like structures was dependent on the presence of vimentin-positive fibroblasts in culture. The sinusoid-like structures formed by hepatocytes and pure populations of endothelial cells collapsed after 10 days in culture. In contrast, culture of hepatocytes with fibroblast-contaminated human dermal microvascular endothelial cells or a combination of human umbilical vein endothelial cells and normal human dermal fibroblasts resulted in stable sinusoid-like structures surrounded by a fibroblastic capsule that maintained liver specific functions for several months in vitro. These results demonstrate that specification of endothelial cell position ultimately determines hepatocyte position in vitro, suggesting that similar interactions might occur in vivo. The novelty of the culture's sinusoid-like organization and long-term function suggest a new model for the study of liver toxicity, iscaemia/reperfusion injury, and fibrosis.
AB - A major goal of liver tissue engineering is to understand how the constituent cell types interact to achieve liver-specific structure and function. Here we show that hepatocytes migrate toward and adhere to endothelial vascular structures formed on Matrigel in vitro, and that hepatocyte recruitment is dependent on endothelium-derived hepatocyte growth factor. The hepatocyte-decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and a lumen. The sinusoid-like structures retained cytochrome P450 expression and activity, in addition to stable albumin expression and secretion rate for over 2 months in vitro. The stability of the sinusoid-like structures was dependent on the presence of vimentin-positive fibroblasts in culture. The sinusoid-like structures formed by hepatocytes and pure populations of endothelial cells collapsed after 10 days in culture. In contrast, culture of hepatocytes with fibroblast-contaminated human dermal microvascular endothelial cells or a combination of human umbilical vein endothelial cells and normal human dermal fibroblasts resulted in stable sinusoid-like structures surrounded by a fibroblastic capsule that maintained liver specific functions for several months in vitro. These results demonstrate that specification of endothelial cell position ultimately determines hepatocyte position in vitro, suggesting that similar interactions might occur in vivo. The novelty of the culture's sinusoid-like organization and long-term function suggest a new model for the study of liver toxicity, iscaemia/reperfusion injury, and fibrosis.
UR - http://www.scopus.com/inward/record.url?scp=33746841799&partnerID=8YFLogxK
U2 - 10.1089/ten.2006.12.1627
DO - 10.1089/ten.2006.12.1627
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C2 - 16846358
AN - SCOPUS:33746841799
SN - 1076-3279
VL - 12
SP - 1627
EP - 1638
JO - Tissue Engineering
JF - Tissue Engineering
IS - 6
ER -