Dataset Information

Molecular Imaging of Human Skeletal Myoblasts (huSKM) in Mouse Post-Infarction Myocardium.

ABSTRACT: Current treatment protocols for myocardial infarction improve the outcome of disease to some extent but do not provide the clue for full regeneration of the heart tissues. An increasing body of evidence has shown that transplantation of cells may lead to some organ recovery. However, the optimal stem cell population has not been yet identified. We would like to propose a novel pro-regenerative treatment for post-infarction heart based on the combination of human skeletal myoblasts (huSkM) and mesenchymal stem cells (MSCs). huSkM native or overexpressing gene coding for Cx43 (huSKMCx43) alone or combined with MSCs were delivered in four cellular therapeutic variants into the healthy and post-infarction heart of mice while using molecular reporter probes. Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) performed right after cell delivery and 24 h later revealed a trend towards an increase in the isotopic uptake in the post-infarction group of animals treated by a combination of huSkMCx43 with MSC. Bioluminescent imaging (BLI) showed the highest increase in firefly luciferase (fluc) signal intensity in post-infarction heart treated with combination of huSkM and MSCs vs. huSkM alone (p < 0.0001). In healthy myocardium, however, nanoluciferase signal (nanoluc) intensity varied markedly between animals treated with stem cell populations either alone or in combinations with the tendency to be simply decreased. Therefore, our observations seem to show that MSCs supported viability, engraftment, and even proliferation of huSkM in the post-infarction heart.

SUBMITTER: Fiedorowicz K

PROVIDER: S-EPMC8509689 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Molecular Imaging of Human Skeletal Myoblasts (huSKM) in Mouse Post-Infarction Myocardium.

Fiedorowicz Katarzyna K Wargocka-Matuszewska Weronika W Ambrożkiewicz Karolina A KA Rugowska Anna A Cheda Łukasz Ł Fiedorowicz Michał M Zimna Agnieszka A Drabik Monika M Borkowski Szymon S Świątkiewicz Maciej M Bogorodzki Piotr P Grieb Paweł P Hamankiewicz Paulina P Kolanowski Tomasz J TJ Rozwadowska Natalia N Kozłowska Urszula U Klimczak Aleksandra A Kolasiński Jerzy J Rogulski Zbigniew Z Kurpisz Maciej M

International journal of molecular sciences 20211008 19

Current treatment protocols for myocardial infarction improve the outcome of disease to some extent but do not provide the clue for full regeneration of the heart tissues. An increasing body of evidence has shown that transplantation of cells may lead to some organ recovery. However, the optimal stem cell population has not been yet identified. We would like to propose a novel pro-regenerative treatment for post-infarction heart based on the combination of human skeletal myoblasts (huSkM) and me ...[more]

PMID: 34639225

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Project description:BackgroundTransplanting myogenic cells and scaffolds for tissue engineering in skeletal muscle have shown inconsistent results. One of the limiting factors is neovascularization at the recipient site. Low intensity shockwave therapy (Li-SWT) has been linked to increased tissue regeneration and vascularization, both integral to survival and integration of transplanted cells. This study was conducted to demonstrate the response of myoblasts and skeletal muscle to Li-SWT.MethodPrimary isolated human myoblasts and explants were treated with low intensity shockwaves and subsequently cell viability, proliferation and differentiation were tested. Cardiotoxin induced injury was created in tibialis anterior muscles of 28 mice, and two days later, the lesions were treated with 500 impulses of Li-SWT on one of the legs. The treatment was repeated every third day of the period and ended on day 14 after cardiotoxin injection.. The animals were followed up and documented up to 21 days after cardiotoxin injury.ResultsLi-SWT had no significant effect on cell death, proliferation, differentiation and migration, the explants however showed decreased adhesion. In the animal experiments, qPCR studies revealed a significantly increased expression of apoptotic, angiogenic and myogenic genes; expression of Bax, Bcl2, Casp3, eNOS, Pax7, Myf5 and Met was increased in the early phase of regeneration in the Li-SWT treated hind limbs. Furthermore, a late accumulative angiogenic effect was demonstrated in the Li-SWT treated limbs by a significantly increased expression of Angpt1, eNOS, iNOS, Vegfa, and Pecam1.ConclusionTreatment was associated with an early upregulation in expression of selected apoptotic, pro-inflammatory, angiogenic and satellite cell activating genes after muscle injury. It also showed a late incremental effect on expression of pro-angiogenic genes. However, we found no changes in the number of PAX7 positive cells or blood vessel density in Li-SWT treated and control muscle. Furthermore, Li-SWT in the selected doses did not decrease survival, proliferation or differentiation of myoblasts in vitro.

Project description:BackgroundCardiac MRI feature tracking (FT) allows objective assessment of segmental left ventricular (LV) function following a myocardial infarction (MI), but its utilization in sheep, where interventions can be tested, is lacking.PurposeTo apply and validate FT in a sheep model of MI and describe post-MI LV remodeling.Study typeAnimal model, longitudinal.Animal modelEighteen lambs (6 months, male, n = 14; female, n = 4; 25.2 ± 4.5 kg).Field strength/sequenceTwo-dimensional balanced steady-state free precession (bSSFP) and 3D inversion recovery fast low angle shot (IR-FLASH) sequences at 3 T.AssessmentSeven lambs underwent test-retest imaging to assess FT interstudy reproducibility. MI was induced in the remaining 11 by coronary ligation with MRI being undertaken before and 15 days post-MI. Injury size was measured by late gadolinium enhancement (LGE) and LV volumes, LV mass, ejection fraction (LVEF), and wall thickness (LVWT) were measured, with FT measures of global and segmental radial, circumferential, and longitudinal strain.Statistical testsSampling variability, inter-study, intra and interobserver reproducibility were assessed using Pearson's correlation, Bland-Altman analyses, and intra-class correlation coefficients (ICC). Diagnostic performance of segmental strain to predict LGE was assessed using receiver operating characteristic curve analysis. Significant differences were considered P < 0.05.ResultsInter-study reproducibility of FT was overall good to excellent, with global strain being more reproducible than segmental strain (ICC = 0.89-0.98 vs. 0.77-0.96). MI (4.0 ± 3.7% LV mass) led to LV remodeling, as evident by significantly increased LV volumes and LV mass, and significantly decreased LVWT in injured regions, while LVEF was preserved (54.9 ± 6.9% vs. 55.6 ± 5.7%; P = 0.778). Segmental circumferential strain (CS) correlated most strongly with LGE. Basal and mid- CS increased significantly, while apical CS significantly decreased post-MI.Data conclusionFT is reproducible and compensation by hyperkinetic remote myocardium may manifest as overall preserved global LV function.Evidence levelN/A TECHNICAL EFFICACY: Stage 2.

Dataset Information

Molecular Imaging of Human Skeletal Myoblasts (huSKM) in Mouse Post-Infarction Myocardium.

Publications

Molecular Imaging of Human Skeletal Myoblasts (huSKM) in Mouse Post-Infarction Myocardium.

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