Weiss, T.S.; Lichtenauer, M.; Kirchner, S.; Stock, P.; Aurich, H.; Christ, B.; Brockhoff, G.; Kunz-Schughart, L.A.; Jauch, Karl-Walter; Schlitt, H.-J.; Thasler, Wolfgang E.
Hepatic progenitor cells from adult human livers for cell transplantation.
In: Gut, Vol. 57: pp. 1129-1138
Objective: Liver regeneration is mainly based on cellular
self-renewal including progenitor cells. Efforts have been
made to harness this potential for cell transplantation, but
shortage of hepatocytes and premature differentiated
progenitor cells from extra-hepatic organs are limiting
factors. Histological studies implied that resident cells in
adult liver can proliferate, have bipotential character and
may be a suitable source for cell transplantation.
Methods: Particular cell populations were isolated after
adequate tissue dissociation. Single cell suspensions were
purified by Thy-1 positivity selection, characterised in vitro
and transplanted in immunodeficient Pfp/Rag2 mice.
Results: Thy-1+ cells that are mainly found in the portal
tract and the surrounding parenchyma, were isolated from
surgical liver tissue with high yields from specimens with
histological signs of regeneration. Thy-1+ cell populations
were positive for progenitor (CD34, c-kit, CK14, M2PK,
OV6), biliary (CK19) and hepatic (HepPar1) markers
revealing their progenitor as well as hepatic and biliary
nature. The potential of Thy-1+ cells for differentiation in
vitro was demonstrated by increased mRNA and protein
expression for hepatic (CK18, HepPar1) and biliary (CK7)
markers during culture while progenitor markers CK14,
chromogranin A and nestin were reduced. After
transplantation of Thy-1+ cells into livers of immunodeficient
mice, engraftment was predominantly seen in the
periportal portion of the liver lobule. Analysis of in situ
material revealed that transplanted cells express human
hepatic markers HepPar1 and albumin, indicating functional
Conclusion: Bipotential progenitor cells from human
adult livers can be isolated using Thy-1 and might be a
potential candidate for cell treatment in liver diseases.