title: Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells.
abstract: OBJECTIVE
  Less invasive therapies using mesenchymal stem cells (MSC) are being developed to treat patients with severe liver cirrhosis. MSC constitute a promising cell source for regenerative therapy and are frequently isolated from bone marrow (BMSC) or adipose tissue (ASC). Therefore, this study assessed the characteristics of these two cell types and their safety for cell infusion.
  
  
  METHODS
  In vitro, exhaustive genetic analysis was performed using human (h)BMSC and hASC. Subsequently, the expression of mRNA and protein was evaluated. In vivo, mouse (m)BMSC or mASC was infused into serial mice via the peripheral vein, and 24-h survival rate, prothrombin time and cause of death were analyzed.
  
  
  RESULTS
  On polymerase chain reaction, western blotting, enzyme-linked immunoassay and fluorescence-activated cell sorting, tissue factor was found to be expressed at higher levels in hASC than in hBMSC. Prothrombin time in mice infused with mASC (>120 s) was markedly longer than that of untreated mice (6.5 ± 1.7 s) and that of mice infused with BMSC (6.7 ± 0.8 s) (P < 0.001), indicating that pro-coagulation activity was potently enhanced after ASC infusion. The 24-h survival rates in the mASC- and mBMSC-infused groups were 46.4% (13/28) and 95.5% (21/22), respectively; in the former, the rate decreased with increasing number of infused mASC. This cell number-dependent effect was not observed with mBMSC. A histopathological analysis of mice that died immediately following mASC infusion revealed multiple thrombi in the blood vessels of the lungs.
  
  
  CONCLUSIONS
  These results indicate that BMSC are a superior and safer cell source for regenerative therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Shiratsuki
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Takami
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujisawa
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: Guzel
authors.initials: G
authors.lastname: Burganova
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Quintanilha
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
keywords: matrix metalloproteinase; mesenchymal stem cell; pro-coagulation; tissue factor