title: Adipose tissue-derived mesenchymal stem cell-based liver gene delivery.
abstract: OBJECTIVE
  The adipose tissue represents an accessible, abundant, and replenishable source of adult stem cells for potential applications in regenerative medicine. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) resemble bone marrow-derived mesenchymal stem cells (BM-MSCs) with respect to morphology, immune-phenotype, and multiple differentiation capability. In the present study, we investigated the feasibility of AT-MSC-based liver gene delivery for the treatment of alpha 1-antitrypsin deficiency.
  
  
  METHODS
  Mouse AT-MSCs were transduced by rAAV vectors and transplanted into the mouse liver.
  
  
  RESULTS
  We showed that AT-MSCs can be transduced by recombinant adeno-associated viral vector serotype 1 (rAAV1-CB-hAAT). After transplanting to the mouse liver, ex vivo transduced AT-MSCs expressed the transgene product, human alpha 1-antitrypsin (hAAT). Importantly, serum levels of hAAT were sustained and no anti-hAAT antibody was detected in any recipients.
  
  
  CONCLUSIONS
  These results demonstrated that AT-MSCs can be transduced by rAAV vectors, engrafted into recipient livers, contribute to liver regeneration, and serve as a platform for transgene expression without eliciting an immune response. AT-MSC-based gene therapy presents a novel approach for the treatment of liver diseases, such as AAT deficiency.
authors.affiliation: Departments of Pharmaceutics, University of Florida, Gainesville, FL, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Lu
authors.forename: Marda
authors.initials: M
authors.lastname: Jorgensen
authors.forename: Bryon
authors.initials: B
authors.lastname: Petersen
authors.forename: Sihong
authors.initials: S
authors.lastname: Song
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019076:Transgenes / Q000235:genetics / Q000276:immunology; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics* / Q000276:immunology; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics / Q000276:immunology / Q000628:therapy*
chemical_list: D000906:Antibodies; D000515:alpha 1-Antitrypsin