Hepatic progenitor cells from adult human livers for cell transplantation.

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 engraftment.
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.