Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma
While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize th...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/4658503 |
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| author | Deana Haralampieva Souzan Salemi Thomas Betzel Ivana Dinulovic Stefanie D. Krämer Roger Schibli Tullio Sulser Christoph Handschin Simon M. Ametamey Daniel Eberli |
| author_facet | Deana Haralampieva Souzan Salemi Thomas Betzel Ivana Dinulovic Stefanie D. Krämer Roger Schibli Tullio Sulser Christoph Handschin Simon M. Ametamey Daniel Eberli |
| author_sort | Deana Haralampieva |
| collection | DOAJ |
| description | While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1α), key regulator of exercise-mediated adaptation. Moreover, we aimed at establishing a feasible methodology for noninvasive PET visualization of implanted cells and their microenvironment in muscle crush injury model. PGC-1α-bioengineered muscles showed enhanced marker expression for myogenesis (α-actinin, MyHC, and Desmin), vascularization (VEGF), neuronal (ACHE), and mitochondrial (COXIV) activity. Consistently, use of hPGC-1α_hMPCs produced significantly increased contractile force one to three weeks postinjury. PET imaging showed distinct differences in radiotracer signals ([18F]Fallypride and [11C]Raclopride (both targeting dopamine 2 receptors (D2R)) and [64Cu]NODAGA-RGD (targeting neovascularization)) between GFP_hMPCs and hD2R_hPGC-1α_hMPCs. After muscle harvesting, inflammation levels were in parallel to radiotracer uptake amount, with significantly lower uptake in hPGC-1α overexpressing samples. In summary, we facilitated early functional muscle tissue regeneration, introducing a novel approach to improve skeletal muscle regeneration. Besides successful tracking of hMPCs in muscle crush injuries, we showed that in high-inflammation areas, the specificity of radioligands might be significantly reduced, addressing a possible bottleneck of neovascularization PET imaging. |
| format | Article |
| id | doaj-art-acd17b9196ac4495a3b59702b31bcc4e |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-acd17b9196ac4495a3b59702b31bcc4e2025-02-03T05:44:32ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/46585034658503Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after TraumaDeana Haralampieva0Souzan Salemi1Thomas Betzel2Ivana Dinulovic3Stefanie D. Krämer4Roger Schibli5Tullio Sulser6Christoph Handschin7Simon M. Ametamey8Daniel Eberli9Department of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, University of Zürich, Frauenklinikstrasse 10, 8091 Zürich, SwitzerlandDepartment of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, University of Zürich, Frauenklinikstrasse 10, 8091 Zürich, SwitzerlandInstitute for Pharmaceutical Sciences, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, SwitzerlandBiozentrum, Focal Area Growth and Development, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, SwitzerlandInstitute for Pharmaceutical Sciences, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, SwitzerlandInstitute for Pharmaceutical Sciences, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, SwitzerlandDepartment of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, University of Zürich, Frauenklinikstrasse 10, 8091 Zürich, SwitzerlandBiozentrum, Focal Area Growth and Development, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, SwitzerlandInstitute for Pharmaceutical Sciences, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, SwitzerlandDepartment of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, University of Zürich, Frauenklinikstrasse 10, 8091 Zürich, SwitzerlandWhile many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1α), key regulator of exercise-mediated adaptation. Moreover, we aimed at establishing a feasible methodology for noninvasive PET visualization of implanted cells and their microenvironment in muscle crush injury model. PGC-1α-bioengineered muscles showed enhanced marker expression for myogenesis (α-actinin, MyHC, and Desmin), vascularization (VEGF), neuronal (ACHE), and mitochondrial (COXIV) activity. Consistently, use of hPGC-1α_hMPCs produced significantly increased contractile force one to three weeks postinjury. PET imaging showed distinct differences in radiotracer signals ([18F]Fallypride and [11C]Raclopride (both targeting dopamine 2 receptors (D2R)) and [64Cu]NODAGA-RGD (targeting neovascularization)) between GFP_hMPCs and hD2R_hPGC-1α_hMPCs. After muscle harvesting, inflammation levels were in parallel to radiotracer uptake amount, with significantly lower uptake in hPGC-1α overexpressing samples. In summary, we facilitated early functional muscle tissue regeneration, introducing a novel approach to improve skeletal muscle regeneration. Besides successful tracking of hMPCs in muscle crush injuries, we showed that in high-inflammation areas, the specificity of radioligands might be significantly reduced, addressing a possible bottleneck of neovascularization PET imaging.http://dx.doi.org/10.1155/2018/4658503 |
| spellingShingle | Deana Haralampieva Souzan Salemi Thomas Betzel Ivana Dinulovic Stefanie D. Krämer Roger Schibli Tullio Sulser Christoph Handschin Simon M. Ametamey Daniel Eberli Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma Stem Cells International |
| title | Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma |
| title_full | Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma |
| title_fullStr | Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma |
| title_full_unstemmed | Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma |
| title_short | Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma |
| title_sort | injected human muscle precursor cells overexpressing pgc 1α enhance functional muscle regeneration after trauma |
| url | http://dx.doi.org/10.1155/2018/4658503 |
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