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.
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, humanalpha 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: J Rogers; N Kalsheker; S Wallis; A Speer; C H Coutelle; D Woods; S E Humphries Journal: Biochem Biophys Res Commun Date: 1983-10-31 Impact factor: 3.575
Authors: Li Zhong; Baozheng Li; Cathryn S Mah; Lakshmanan Govindasamy; Mavis Agbandje-McKenna; Mario Cooper; Roland W Herzog; Irene Zolotukhin; Kenneth H Warrington; Kirsten A Weigel-Van Aken; Jacqueline A Hobbs; Sergei Zolotukhin; Nicholas Muzyczka; Arun Srivastava Journal: Proc Natl Acad Sci U S A Date: 2008-05-29 Impact factor: 11.205
Authors: Katarina Le Blanc; Francesco Frassoni; Lynne Ball; Franco Locatelli; Helene Roelofs; Ian Lewis; Edoardo Lanino; Berit Sundberg; Maria Ester Bernardo; Mats Remberger; Giorgio Dini; R Maarten Egeler; Andrea Bacigalupo; Willem Fibbe; Olle Ringdén Journal: Lancet Date: 2008-05-10 Impact factor: 79.321
Authors: Yue Yu; James E Fisher; Joseph B Lillegard; Brian Rodysill; Bruce Amiot; Scott L Nyberg Journal: Liver Transpl Date: 2012-01 Impact factor: 5.799
Authors: Kevin Ni; Muhammad Umair Mukhtar Mian; Catherine Meador; Amar Gill; Daria Barwinska; Danting Cao; Matthew J Justice; Di Jiang; Niccolette Schaefer; Kelly S Schweitzer; Hong Wei Chu; Keith L March; Irina Petrache Journal: Stem Cells Dev Date: 2017-09-21 Impact factor: 3.272