title: Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure.
abstract: 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 CCl(4)-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.
authors: Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens-BRFAA, Athens, Greece.
authors: Dimitra S
authors: DS
authors: Zagoura
authors: Maria G
authors: MG
authors: Roubelakis
authors: Vasiliki
authors: V
authors: Bitsika
authors: Ourania
authors: O
authors: Trohatou
authors: Kalliopi I
authors: KI
authors: Pappa
authors: Alkistis
authors: A
authors: Kapelouzou
authors: Aristidis
authors: A
authors: Antsaklis
authors: Nicholas P
authors: NP
authors: Anagnou
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D049452:Green Fluorescent Proteins; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D017114:Liver Failure, Acute / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D040081:Protein Array Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma