Epicardial Transplantation of Adipose Mesenchymal Stromal Cell Sheets Promotes Epicardial Activation and Stimulates Angiogenesis in Myocardial Infarction (Experimental Study)

Konstantin V Dergilev,Sofia V Pavlova,Anastasia V Komova,Irina B Beloglazova,Zoya I Tsokolaeva,Yelena V Parfyonova,Dmitry O Traktuev

doi:10.15360/1813-9779-2019-6-38-49

Abstract

Aim: to evaluate the impact of tissue-engineered structures (TES) transplantation based on mesenchymal stromal cell (MSC) sheets in myocardial infarction on the activation of the epicardial cell pool and vascularization of the damaged zone.Materials and methods. Mesenchymal stromal cells were obtained from samples of subcutaneous fat of Wistar rats and C57Bl/6 mice. Tissue engineering structures were obtained by culturing cell sheets on thermosensitive plates (Nunc Dishes with UpCell Surface). Transplantation of TESs was performed after myocardial infarction modeling in rats by ligation of the anterior descending coronary artery. Transplant cells and damaged zones were assessed using immunofluorescent staining of myocardial cryosections. The impact of MSC secretion products on the migration activity of epicardial cells in vitro was evaluated using the explant culture method.Results. MSCs in TESs after transplantation remain viable and induce activation of the epicardial cell pool and local increase of the damaged zone vascularization. The in vitro experiments showed that the conditioned environment of MSCs stimulates the migratory activity of epicardial cells and initiates the formation of activated Wt1/POD1 precursor cells.Conclusion. TES transplantation on the basis of MSC sheets seems to be a promising approach for effective delivery of viable cells into myocardium to activate the epicardial cellular niche and reparative angiogenesis.

Highlights

Высокоэффективные процессы репаративной регенерации миокарда характерные для низших позвоночных и рыб, крайне слабо представлены у млекопитающих, что не позволяет миокарду полноценно восстанавливаться при обширных повреждениях и лежит в основе развития многих кардиологических заболеваний
tissue-engineered structures (TES) transplantation on the basis of mesenchymal stromal cell (MSC) sheets seems to be a promising approach for effective delivery of viable cells into myocardium to activate the epicardial cellular niche and reparative angiogenesis
We have suggested that the transplantation of mesenchymal stromal cells (MSCs) sheets from adipose tissue to the heart surface may activate a pool of epicardial precursor cells participating in reparation by entering the epithelial-mesenchymal transition (EMT) with further differentiation, as well as through paracrine mechanisms

Summary

Introduction

Высокоэффективные процессы репаративной регенерации миокарда характерные для низших позвоночных и рыб, крайне слабо представлены у млекопитающих, что не позволяет миокарду полноценно восстанавливаться при обширных повреждениях и лежит в основе развития многих кардиологических заболеваний. Решение этой проблемы лежит в области раскрытия эндогенных механизмов, регулирующих процессы репаративной регенерации в сердце, и создания на этой основе новых технологий для их стимуляции. Участие эпикарда в репарации сердца осуществляется посредством паракринных влияний, в частности, секреции факторов роста, прежде всего, Highly effective reparative myocardial regeneration, typical for lower vertebrates and fish, is extremely poorly represented in mammals, which does not allow the myocardium to fully recover from extensive damage and underlies various heart diseases. The problem solution lies in the discovery of endogenous mechanisms regulating the reparative regeneration in the heart and creation of new technologies for their stimulation

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Conclusion