Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation
Muscle precursor cells (MPCs) are activated satellite cells capable of muscle fiber reconstruction. Therefore, autologous MPC transplantation is envisioned for the treatment of muscle diseases. However, the density of MPCs, as well as their proliferation and differentiation potential, gradually decl...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-06-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368917X694868 |
| _version_ | 1818311953663131648 |
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| author | Deana Haralampieva Souzan Salemi Ivana Dinulovic Tullio Sulser Simon M. Ametamey Christoph Handschin Daniel Eberli M.D., Ph.D. |
| author_facet | Deana Haralampieva Souzan Salemi Ivana Dinulovic Tullio Sulser Simon M. Ametamey Christoph Handschin Daniel Eberli M.D., Ph.D. |
| author_sort | Deana Haralampieva |
| collection | DOAJ |
| description | Muscle precursor cells (MPCs) are activated satellite cells capable of muscle fiber reconstruction. Therefore, autologous MPC transplantation is envisioned for the treatment of muscle diseases. However, the density of MPCs, as well as their proliferation and differentiation potential, gradually declines with age. The goals of this research were to genetically modify human MPCs (hMPCs) to overexpress the peroxisome proliferator-activated receptor γ coactivator (PGC-1α), a key regulator of exercise-mediated adaptation, and thereby to enhance early skeletal muscle formation and quality. We were able to confirm the sustained myogenic phenotype of the genetically modified hMPCs. While maintaining their viability and proliferation potential, PGC-1α-modified hMPCs showed an enhanced myofiber formation capacity in vitro. Engineered muscle tissues were harvested 1, 2, and 4 weeks after subcutaneous injection of cell–collagen suspensions, and histological analysis confirmed the earlier myotube formation in PGC-1α-modified samples, predominantly of slow-twitch myofibers. Increased contractile protein levels were detected by Western blot. In summary, by genetically modifying hMPCs to overexpress PGC-1α, we were able to promote early muscle fiber formation in vitro and in vivo, with an initial switch to slow-type myofibers. Therefore, overexpressing PGC-1α is a novel strategy to further enhance skeletal muscle tissue engineering. |
| first_indexed | 2024-12-13T08:10:09Z |
| format | Article |
| id | doaj.art-6e00136f8a8b4034988f4021cefdd113 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T08:10:09Z |
| publishDate | 2017-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-6e00136f8a8b4034988f4021cefdd1132022-12-21T23:54:14ZengSAGE PublishingCell Transplantation0963-68971555-38922017-06-012610.3727/096368917X694868Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue FormationDeana Haralampieva0Souzan Salemi1Ivana Dinulovic2Tullio Sulser3Simon M. Ametamey4Christoph Handschin5Daniel Eberli M.D., Ph.D.6Zurich Center for Integrative Human Physiology (ZIHP), University of Zörich, Zörich, SwitzerlandLaboratory for Tissue Engineering and Stem Cell Therapy, Department of Urology, University Hospital Zurich and University of Zörich, Zörich, SwitzerlandBiozentrum, Focal Area Growth and Development, University of Basel, Basel, SwitzerlandLaboratory for Tissue Engineering and Stem Cell Therapy, Department of Urology, University Hospital Zurich and University of Zörich, Zörich, SwitzerlandInstitute of Pharmaceutical Sciences, ETH Zörich, Zörich, SwitzerlandBiozentrum, Focal Area Growth and Development, University of Basel, Basel, SwitzerlandZurich Center for Integrative Human Physiology (ZIHP), University of Zörich, Zörich, SwitzerlandMuscle precursor cells (MPCs) are activated satellite cells capable of muscle fiber reconstruction. Therefore, autologous MPC transplantation is envisioned for the treatment of muscle diseases. However, the density of MPCs, as well as their proliferation and differentiation potential, gradually declines with age. The goals of this research were to genetically modify human MPCs (hMPCs) to overexpress the peroxisome proliferator-activated receptor γ coactivator (PGC-1α), a key regulator of exercise-mediated adaptation, and thereby to enhance early skeletal muscle formation and quality. We were able to confirm the sustained myogenic phenotype of the genetically modified hMPCs. While maintaining their viability and proliferation potential, PGC-1α-modified hMPCs showed an enhanced myofiber formation capacity in vitro. Engineered muscle tissues were harvested 1, 2, and 4 weeks after subcutaneous injection of cell–collagen suspensions, and histological analysis confirmed the earlier myotube formation in PGC-1α-modified samples, predominantly of slow-twitch myofibers. Increased contractile protein levels were detected by Western blot. In summary, by genetically modifying hMPCs to overexpress PGC-1α, we were able to promote early muscle fiber formation in vitro and in vivo, with an initial switch to slow-type myofibers. Therefore, overexpressing PGC-1α is a novel strategy to further enhance skeletal muscle tissue engineering.https://doi.org/10.3727/096368917X694868 |
| spellingShingle | Deana Haralampieva Souzan Salemi Ivana Dinulovic Tullio Sulser Simon M. Ametamey Christoph Handschin Daniel Eberli M.D., Ph.D. Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation Cell Transplantation |
| title | Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation |
| title_full | Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation |
| title_fullStr | Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation |
| title_full_unstemmed | Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation |
| title_short | Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation |
| title_sort | human muscle precursor cells overexpressing pgc 1α enhance early skeletal muscle tissue formation |
| url | https://doi.org/10.3727/096368917X694868 |
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