Human monocyte-derived neohepatocytes: a promising alternative to primary human hepatocytes for autologous cell therapy.
BACKGROUND
There is growing interest in new therapeutic options for the treatment of end-stage liver diseases. In addition to mechanical devices supporting liver function, such as bioreactors, the transplantation of hepatocyte-like cells derived from (adult) stem cells offer great perspectives. We have generated hepatocyte-like (NeoHep) cells from terminally differentiated peripheral blood monocytes and, in this study, have evaluated these cells as a possible tool for autologous cell therapy.


METHODS
Peripheral blood monocytes were cultured under conditions that promote hepatocyte-like differentiation and were characterized for hepatocyte marker expression by reverse-transcriptase polymerase chain reaction, immunohistochemistry, and immunoblotting and for specific secretory and metabolic functions with the appropriate biochemical assays.


RESULTS
NeoHep cells resembled primary human hepatocytes with respect to morphology, expression of hepatocyte markers (albumin, cytochrome P450 isoenzymes, asialoglycoprotein receptor, coagulation factor VII), various secretory and metabolic functions (albumin secretion, urea production, lactate formation, and lactate dehydrogenase and aspartate transaminase release), and drug detoxification activities (phase I metabolization of ethoxycoumarin into 7OH-coumarin after stimulation with 3-methylcholanthren, induction of CYP3A4 activity, and phase II metabolization through UDP-glucuronidation of 4-methyl-umbelliferone).


CONCLUSIONS
These data convincingly show that NeoHep cells display a phenotype and specific in vitro metabolic functions that are quantitatively and qualitatively comparable in part with those of primary human hepatocytes. These cells could thus be clinically applied in an autologous setting for the treatment of end-stage liver diseases or for improving liver function in patients who have undergone critical liver-mass resection.
Ruhnke
Maren
M
Department of General and Thoracic Surgery, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Nussler
Andreas K
AK
Ungefroren
Hendrik
H
Hengstler
Jan G
JG
Kremer
Bernd
B
Hoeckh
Wolfgang
W
Gottwald
Thomas
T
Heeckt
Peter
P
Fandrich
Fred
F
D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D009000:Monocytes / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014182:Transplantation, Autologous
D015415:Biomarkers; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human