TY - JOUR
T1 - Growth of normal human hepatocytes in primary culture
T2 - Effect of hormones and growth factors on DNA synthesis
AU - Ismail, Tariq
AU - Howl, John
AU - Wheatley, Mark
AU - McMaster, Paul
AU - Neuberger, James M.
AU - Strain, Alastair J.
N1 - Free access
PY - 1991/12
Y1 - 1991/12
N2 - Although the ability of hormones and growth factors to stimulate DNA synthesis in rat hepatocytes has been investigated extensively, no such study of human hepatocytes has been reported. Here we describe a series of experiments to identify those factors that regulate human hepatocyte DNA synthesis in vitro and which therefore may play a role in the control of human liver regeneration. Human hepatocytes were isolated from normal liver tissue obtained after graft reduction for transplantation into pediatric recipients. Cells were maintained in culture for up to 5 days, and DNA synthesis was determined. Hydroxyurea reduced [3H]thymidine incorporation into DNA by 95%, indicating replicative DNA synthesis. As previously found with rat hepatocytes, epidermal growth factor and transforming growth factor‐α stimulated DNA synthesis at low nanomolar concentrations; transforming growth factor‐α was slightly more potent. Although the overall rate of thymidine incorporation was lower than that for rodent cells, human hepatocytes were sensitive to lower concentrations of these growth factors, and the degree of stimulation was similar. Conversely, transforming growth factor‐β inhibited DNA synthesis at low picomolar levels. By contrast (unlike rat hepatocytes), arginine‐vasopressin failed to initiate or potentiate DNA synthesis in human cells. These data indicate that normal human hepatocytes can respond to low concentrations of growth promoters or inhibitors, previously shown to have activity on rat hepatocytes. These factors may then play a role in control of human liver growth. However, important species differences are apparent, highlighting the limitations of extrapolating from animal studies to humans.
AB - Although the ability of hormones and growth factors to stimulate DNA synthesis in rat hepatocytes has been investigated extensively, no such study of human hepatocytes has been reported. Here we describe a series of experiments to identify those factors that regulate human hepatocyte DNA synthesis in vitro and which therefore may play a role in the control of human liver regeneration. Human hepatocytes were isolated from normal liver tissue obtained after graft reduction for transplantation into pediatric recipients. Cells were maintained in culture for up to 5 days, and DNA synthesis was determined. Hydroxyurea reduced [3H]thymidine incorporation into DNA by 95%, indicating replicative DNA synthesis. As previously found with rat hepatocytes, epidermal growth factor and transforming growth factor‐α stimulated DNA synthesis at low nanomolar concentrations; transforming growth factor‐α was slightly more potent. Although the overall rate of thymidine incorporation was lower than that for rodent cells, human hepatocytes were sensitive to lower concentrations of these growth factors, and the degree of stimulation was similar. Conversely, transforming growth factor‐β inhibited DNA synthesis at low picomolar levels. By contrast (unlike rat hepatocytes), arginine‐vasopressin failed to initiate or potentiate DNA synthesis in human cells. These data indicate that normal human hepatocytes can respond to low concentrations of growth promoters or inhibitors, previously shown to have activity on rat hepatocytes. These factors may then play a role in control of human liver growth. However, important species differences are apparent, highlighting the limitations of extrapolating from animal studies to humans.
UR - http://www.scopus.com/inward/record.url?scp=0026352219&partnerID=8YFLogxK
UR - https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.1840140622
U2 - 10.1002/hep.1840140622
DO - 10.1002/hep.1840140622
M3 - Article
C2 - 1959857
AN - SCOPUS:0026352219
SN - 0270-9139
VL - 14
SP - 1076
EP - 1082
JO - Hepatology
JF - Hepatology
IS - 6
ER -