Losartan Enhances the Success of Myoblast Transplantation
Duchenne muscular dystrophy is a recessive X-linked genetic disease caused by dystrophin gene mutations. Cell therapy can be a potential approach aiming to introduce a functional dystrophin in the dystrophic patient myofibers. However, this strategy produced so far limited results. Transforming grow...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-02-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368911X576045 |
| _version_ | 1831730306474835968 |
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| author | Raouia Fakhfakh Yann Lamarre Daniel Skuk Jacques P. Tremblay Ph.D. |
| author_facet | Raouia Fakhfakh Yann Lamarre Daniel Skuk Jacques P. Tremblay Ph.D. |
| author_sort | Raouia Fakhfakh |
| collection | DOAJ |
| description | Duchenne muscular dystrophy is a recessive X-linked genetic disease caused by dystrophin gene mutations. Cell therapy can be a potential approach aiming to introduce a functional dystrophin in the dystrophic patient myofibers. However, this strategy produced so far limited results. Transforming growth factor-β (TGF-β) is a negative regulator of skeletal muscle development and is responsible for limiting myogenic regeneration. The combination of TGF-β signaling inhibition with myoblast transplantation can be an effective therapeutic approach in dystrophin-deficient patients. Our aim was to verify whether the success of human myoblast transplantation in immunodeficient dystrophic mice is enhanced with losartan, a molecule that downregulates TGF-β expression. In vitro, blocking TGF-β activity with losartan increased proliferation and fusion and decreased apoptosis in human myoblasts. In vivo, human myoblasts were transplanted in mice treated with oral losartan. Immunodetection of human dystrophin in tibialis anterior cross sections 1 month posttransplantation revealed more human dystrophin-positive myofibers in these mice than in nontreated dystrophic mice. Thus, blocking the TGF-β signal with losartan treatment improved the success of myoblast transplantation probably by increasing myoblast proliferation and fusion, decreasing macrophage activation, and changing the expression of myogenic regulator factors. |
| first_indexed | 2024-12-21T09:42:47Z |
| format | Article |
| id | doaj.art-af81e133e53e42d78bc5718834cb5564 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-21T09:42:47Z |
| publishDate | 2012-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-af81e133e53e42d78bc5718834cb55642022-12-21T19:08:25ZengSAGE PublishingCell Transplantation0963-68971555-38922012-02-012110.3727/096368911X576045Losartan Enhances the Success of Myoblast TransplantationRaouia Fakhfakh0Yann Lamarre1Daniel Skuk2Jacques P. Tremblay Ph.D.3Unité de recherche de recherche en Génétique Humaine, Centre de recherche de CHUL, CHUQ, Faculté de médecine, Université Laval, Québec, QC, CanadaUnité de recherche de recherche en Génétique Humaine, Centre de recherche de CHUL, CHUQ, Faculté de médecine, Université Laval, Québec, QC, CanadaUnité de recherche de recherche en Génétique Humaine, Centre de recherche de CHUL, CHUQ, Faculté de médecine, Université Laval, Québec, QC, CanadaUnité de recherche de recherche en Génétique Humaine, Centre de recherche de CHUL, CHUQ, Faculté de médecine, Université Laval, Québec, QC, CanadaDuchenne muscular dystrophy is a recessive X-linked genetic disease caused by dystrophin gene mutations. Cell therapy can be a potential approach aiming to introduce a functional dystrophin in the dystrophic patient myofibers. However, this strategy produced so far limited results. Transforming growth factor-β (TGF-β) is a negative regulator of skeletal muscle development and is responsible for limiting myogenic regeneration. The combination of TGF-β signaling inhibition with myoblast transplantation can be an effective therapeutic approach in dystrophin-deficient patients. Our aim was to verify whether the success of human myoblast transplantation in immunodeficient dystrophic mice is enhanced with losartan, a molecule that downregulates TGF-β expression. In vitro, blocking TGF-β activity with losartan increased proliferation and fusion and decreased apoptosis in human myoblasts. In vivo, human myoblasts were transplanted in mice treated with oral losartan. Immunodetection of human dystrophin in tibialis anterior cross sections 1 month posttransplantation revealed more human dystrophin-positive myofibers in these mice than in nontreated dystrophic mice. Thus, blocking the TGF-β signal with losartan treatment improved the success of myoblast transplantation probably by increasing myoblast proliferation and fusion, decreasing macrophage activation, and changing the expression of myogenic regulator factors.https://doi.org/10.3727/096368911X576045 |
| spellingShingle | Raouia Fakhfakh Yann Lamarre Daniel Skuk Jacques P. Tremblay Ph.D. Losartan Enhances the Success of Myoblast Transplantation Cell Transplantation |
| title | Losartan Enhances the Success of Myoblast Transplantation |
| title_full | Losartan Enhances the Success of Myoblast Transplantation |
| title_fullStr | Losartan Enhances the Success of Myoblast Transplantation |
| title_full_unstemmed | Losartan Enhances the Success of Myoblast Transplantation |
| title_short | Losartan Enhances the Success of Myoblast Transplantation |
| title_sort | losartan enhances the success of myoblast transplantation |
| url | https://doi.org/10.3727/096368911X576045 |
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