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

Int J Mol Sci. 2021 Oct 8;22(19):10885. doi: 10.3390/ijms221910885.

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.

Keywords: Bioluminescent Imaging; Magnetic Resonance Imaging; Single-Photon Emission Computed Tomography/Computed Tomography; human skeletal myoblasts; mesenchymal stem cells; promoter reporter gene; technetium.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Genes, Reporter
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Molecular Imaging / methods*
  • Myoblasts, Skeletal / cytology*
  • Myoblasts, Skeletal / metabolism
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardium / metabolism
  • Myocardium / pathology*