Abstract
Purpose. To develop a method of producing tissue-engineered constructs (TECs) on the basis of resident mesenchymal progenitor cells (MPC) of the human heart and to assess the effect of TECs transplantation on regenerative processes in the heart using a model of myocardial infarction in rats.Materials and methods. Human resident MPCs were isolated from the right atrial auricle of CAD patients. A similar protocol was used to obtain MPCs from Wistar rats. The MPC immunophenotype was determined by cytofluorometry. Corresponding TECs were obtained on the basis of MPC sheets of human and rats' hearts. Myocardial infarction in rats was induced by ligation of the anterior descending coronary artery followed by TEC transplantation. Euthanasia was performed 30 days after the transplantation. Histological examination of the implant and vascularization cells, morphometric analysis, tracking of the MPC differentiation ability, determination of the content of growth factors by solid-phase ELISA were carried out. Statistical evaluation of the significance of differences was performed using the Statistica 8.0 software package.Results. The analysis of the obtained cell constructs showed that they consisted of several layers of cells interacting with each other by means of connexin 43 and were characterized by good cell viability as a part TECs. The number of vessels in the peri-infarction area under the transplant from the MPC was significantly higher than that in the reference group with signs of differentiation of cardiac MPCs transplanted into endothelial vascular cells.The increased vascularization was combined with an increase in the area of viable myocardial sites and a decrease in LV cavity dilation. Analysis of the cardiac MPC secretion products showed that they produce the most important growth factors and cytokines that regulate angiogenesis and migration of stem cells.Conclusion. The strategy of using epicardial TEC transplantation based on MPC sheets seems to be a rational approach for effective delivery of viable stem/progenitor cells to the damaged myocardium. The use of TEC helps to reduce or temporarily eliminate the effect of factors that contribute to progressive heart dysfunction by local paracrine exposure and activation of the revascularization processes in the affected zone.
Highlights
Over the past fifty years, heart transplantation has maintained its position as the only option to improve the quality of life of patients with severe heart failure caused by coronary heart disease or cardiomyopathy
Определение содержания ростовых факторов методом твердофазного иммуноферментного анализа (ИФА)
Часть клеток в составе тканеинженерных конструкций (ТИК) экспрессировала маркер пролиферации Ki-67 (84,7±32 на 1000 клеток), что в совокупности с отсутствием маркеров апоптоза, указывает на хорошее поддержание жизthe effectiveness of cell therapy of heart disease, which ensures cell survival and regenerative properties. To ensure these parameters to be included, we developed tissue-engineered constructs (TECs) based on sheets from the cardiac mesenchymal progenitor cells (MPCs) isolated from the samples of the right atrial auricle obtained during CABG
Summary
Over the past fifty years, heart transplantation has maintained its position as the only option to improve the quality of life of patients with severe heart failure caused by coronary heart disease or cardiomyopathy. The delivery of cells by injection in the form of a suspension leads to the death of a significant number of them (up to 90%) both due to mechanical damage when administered through a needle and due to apoptosis (anoikis) caused by impairment of intercellular contacts when transferring cells from the adhesive culture into the suspension. This creates difficulties for dosing, determining the target area of administration and distribution in the myocardium. The purpose of this study was to develop a method of producing such TECs on the basis of resident MPCs of the human heart, as well as to evaluate of the effect of transplantation of these TECs on regenerative processes in the heart using a model of myocardial infarction in rats
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