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Injected Human Muscle Precursor Cells Overexpressing PGC-1α. Enhance Functional Muscle Regeneration after Trauma

Haralampieva, Deana and Salemi, Souzan and Betzel, Thomas and Dinulovic, Ivana and Krämer, Stefanie D. and Schibli, Roger and Sulser, Tullio and Handschin, Christoph and Ametamey, Simon M. and Eberli, Daniel. (2018) Injected Human Muscle Precursor Cells Overexpressing PGC-1α. Enhance Functional Muscle Regeneration after Trauma. Stem cells international, 2018. p. 4658503.

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Abstract

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-1; α; ), 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-1; α; -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-1; α; _hMPCs produced significantly increased contractile force one to three weeks postinjury. PET imaging showed distinct differences in radiotracer signals ([; 18; F]Fallypride and [; 11; C]Raclopride (both targeting dopamine 2 receptors (D2R)) and [; 64; Cu]NODAGA-RGD (targeting neovascularization)) between GFP_hMPCs and hD2R_hPGC-1; α; _hMPCs. After muscle harvesting, inflammation levels were in parallel to radiotracer uptake amount, with significantly lower uptake in hPGC-1; α; 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Hindawi
ISSN:1687-966X
e-ISSN:1687-9678
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:22 Mar 2018 14:31
Deposited On:22 Mar 2018 14:31

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