Τίτλος:
Therapeutic potential of a distinct population of human amniotic fluid
mesenchymal stem cells and their secreted molecules in mice with acute
hepatic failure
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background There is increasing interest in the therapeutic potential of
human mesenchymal stem cells (hMSCs), especially in diseases such as
acute hepatic failure (AHF) that are predominantly caused by a variety
of drugs and viruses. In previous studies, a distinct population termed
human spindle-shaped MSCs were isolated and expanded from second
trimester amniotic fluid (AF-MSCs) and characterised based on their
phenotype, pluripotency and differentiation potential.
Methods AF-MSCs, hepatic progenitor-like (HPL) cells and hepatocyte-like
(HL) cells derived from AF-MSCs were transplanted into CCl4-injured
NOD/SCID mice with the AHF phenotype in order to evaluate their
therapeutic potential. Conditioned medium (CM) derived from AF-MSCs or
HPL cells was then delivered intrahepatically in order to determine
whether the engraftment of the cells or their secreted molecules are the
most important agents for liver repair.
Results Both HPL cells and AF-MSCs were incorporated into CCl4-injured
livers; HPL cell transplantation had a greater therapeutic effect. In
contrast, HL cells failed to engraft and contribute to recovery. In
addition, HPL-CM was found to be more efficient than CM derived from
AF-MSCs in treatment of the liver. Proteome profile analysis of HPL-CM
indicated the presence of anti-inflammatory factors such as interleukins
IL-10, IL-1ra, IL-13 and IL-27 which may induce liver recovery. Blocking
studies of IL-10 secretion from HPL cells confirmed the therapeutic
significance of this cytokine in the AHF mouse model.
Conclusions Human spindle-shaped AF-MSCs or HPL cells might be valuable
tools to induce liver repair and support liver function by cell
transplantation. More importantly, the factors they release may also
play an important role in cell treatment in diseases of the liver.
Συγγραφείς:
Zagoura, Dimitra S.
Roubelakis, Maria G.
Bitsika, Vasiliki and
Trohatou, Ourania
Pappa, Kalliopi I.
Kapelouzou, Alkistis and
Antsaklis, Aristidis
Anagnou, Nicholas P.
Εκδότης:
BMJ Publishing Group
DOI:
10.1136/gutjnl-2011-300908