Journal
JOURNAL OF HEPATOLOGY
Volume 54, Issue 5, Pages 930-938Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2010.07.051
Keywords
Alpha 1 antitrypsin deficiency; Adeno-associated virus (AAV); Liver gene therapy; Liver regeneration
Categories
Funding
- NIDDK [P01-DK58327]
- NHLBI [R21-HL079132]
- Alpha One Foundation
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Background & Aims: 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. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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