Administration of Bone Marrow Derived Mesenchymal Stem Cells into the Liver: Potential to Rescue Pseudoxanthoma Elasticum in a Mouse Model (Abcc6 -/-)

Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder caused by loss-of-function mutations in the ABCC6 gene which is primarily expressed in the liver. There is currently no effective treatment for PXE. In this study, we characterized bone marrow derived mesenchymal stem cell...

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Publicado en:Journal of Biomedicine & Biotechnology Vol. 2012; pp. 1 - 12
Autores principales: Qiujie Jiang, Takahagi, Shunsuke, Uitto, Jouni
Formato: pictorial research tables/charts tracings Journal Article
Publicado: Wiley-Blackwell 2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2012
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      pub: Wiley-Blackwell
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        atl: Administration of Bone Marrow Derived Mesenchymal Stem Cells into the Liver: Potential to Rescue Pseudoxanthoma Elasticum in a Mouse Model (Abcc6 -/-)
      aug:
        au:
          Qiujie Jiang
          Takahagi, Shunsuke
          Uitto, Jouni
        affil: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA
      sug:
        subj:
          Connective Tissue Diseases Therapy
          Stem Cells
          Liver Failure Prevention and Control
          Cell Transplantation Methods
          Funding Source
          Animal Studies
          Mice
          Fluoroimmunoassay
          Flow Cytometry
          Descriptive Statistics
          Data Analysis Software
          Enzyme-Linked Immunosorbent Assay
          T-Tests
          In Vivo Studies
          In Vitro Studies
      ab: Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder caused by loss-of-function mutations in the ABCC6 gene which is primarily expressed in the liver. There is currently no effective treatment for PXE. In this study, we characterized bone marrow derived mesenchymal stem cells (MSCs) and evaluated their ability to contribute to liver regeneration, with the aim to rescue PXE phenotype. The MSCs, isolated from GFP-transgenic mice by magnetic cell sorting, were shown to have high potential for hepatic differentiation, with expression of Abcc6, in culture. These cells were transplanted into the livers of 4-week-old immunodeficient Abcc6-/- mice by intrasplenic injection one day after partial hepatectomy, when peak expression of the stromal cell derived factor-1 (SDF-1) in the liver was observed. Fluorescent bioimaging analyses indicated that transplanted MSCs homed into liver between day 1 and 7, and significant numbers of GFP-positive cells were confirmed in the liver by immunofluorescence. Moreover, enhanced engraftment efficiency was observed with MSCs with high expression levels of the chemokine receptor Cxcr4, a receptor for SDF-1. These data suggest that purified MSCs have the capability of differentiating into hepatic lineages relevant to PXE pathogenesis and may contribute to partial correction of the PXE phenotype.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
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        Journal Article
      ougenre: Article
    language: English
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