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

Katarzyna Fiedorowicz,Karolina A Ambrożkiewicz,Łukasz Cheda,Agnieszka Zimna,Maciej Świątkiewicz,Piotr Bogorodzki,Maciej Kurpisz,Monika Drabik,Michał Fiedorowicz,Paweł Grieb,Szymon Borkowski,Paulina Hamankiewicz,Anna Rugowska,Aleksandra Klimczak,Weronika Wargocka-Matuszewska,Natalia Rozwadowska,Urszula Kozłowska,Jerzy Kolasiński ,Z Rogulski ,Tomasz Kolanowski

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.

Highlights

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide.Pharmacological and surgical treatments improve the outcome of this disease to some extent; known conventional therapies do not provide the regeneration or replacement of the damaged heart tissues
Cells biodistribution was observed using an in vivo imaging system (BLI) for 6 weeks
The results presented demonstrated that cellular therapy based on the combination of human skeletal myoblasts (huSkM) with mesenchymal stem cells was the most beneficial variant for the mouse post-infarction heart

Summary

Introduction

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide.Pharmacological and surgical treatments improve the outcome of this disease to some extent; known conventional therapies do not provide the regeneration or replacement of the damaged heart tissues. An increasing body of evidence has shown that transplantation of stem/progenitor cells may lead to promising recovery of cardiac function [1]. Even though various types of stem/progenitor cells (bone marrow stem cells, skeletal myoblasts (huSkM), mesenchymal stem cells (MSCs), embryonic stem cells, or iPSC-derived cardiomyocytes) have been proposed and tested [2], the optimal cell population has not been identified. The major reason for the poor effects of so far performed cellular therapies was linked to limitations such as cell migration from the target site of their administration, insufficient trans-differentiation or differentiation into adult cardiomyocytes, induction of an arrhythmia, or tumour formation [3]. We suggest that combined cellular therapy using huSkM and MSC should be pursued in order to use the “best features” of a particular cell type

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