Towards on line monitoring the evolution of the myocardium infarction scar with an implantable electrical impedance spectrum monitoring system.

The human heart tissue has a limited capacity for regeneration. Tissue and cellular therapies based on the use of stem cells may be useful alternatives to limit the size of myocardial infarction. In this paper, the preliminary results from an experimental campaign for on-line monitoring of myocardium scar infarction are presented. This study has been carried out under a research project that has as main objective the development and application of a bioactive patch implant for regeneration of myocardial infarction. Electrical Impedance Spectroscopy (EIS) has been chosen as a tissue state monitoring technique. What is presented in this communication is the first results of an implantable EIS measurement system which has been implanted in a subset of the animals corresponding to the control group, along one month. In all the animals, the myocardial infarction was induced by the ligation of the first circumflex marginal artery. In the animal group presented,the bioactive patch scaffold and the electrodes were implanted without the stem cells load. The scaffold is a piece of decellularized human pericardium, lyophilized and rehydrated with hydrogel RAD16-I. Nanogold particles were also placed near the electrodes to improve the electrode area conductivity. The results presented correspond to the subset of animals (n = 5), which had implanted the bioimpedance system monitoring the electrical impedance spectrum in vivo during 1 month. Two electrodes were connected to the bioactive patch implant. A total of 14 logarithmically spaced frequencies were measured every 5 minutes, from 100 Hz to 200 kHz. Results show a convergence of low-frequency and high frequency impedance magnitudes along the measurement period, which is coherent with the scar formation.Postprint (published version

Postinfarction functional recovery driven by a three-dimensional engineered fibrin patch composed of human umbilical cord blood-derived mesenchymal stem cells

© AlphaMed Press. Considerable research has been dedicated to restoring myocardial cell slippage and limiting ventricular remodeling after myocardial infarction (MI). We examined the ability of a three-dimensional (3D) engineered fibrin patch filled with human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to induce recovery of cardiac function after MI. The UCBMSCs were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group). The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSCmice and were markedly reduced in mice treated with fibrin alone and untreated post infarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCsattenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound

Electrical stimulation of cardiac adipose tissue-derived progenitor cells modulates cell phenotype and genetic machinery

A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. Our aim was to examine the effect of electrical stimulation on the cardiodifferentiation potential of cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs). Three different electrical stimulation protocols were tested; the selected protocol consisted of 2 ms monophasic square-wave pulses of 50 mV/cm at 1 Hz over 14 days. Cardiac and subcutaneous ATDPCs were grown on biocompatible patterned surfaces. Cardiomyogenic differentiation was examined by real-time PCR and immunocytofluorescence. In cardiac ATDPCs, MEF2A and GATA-4 were significantly upregulated at day 14 after stimulation, while subcutaneous ATDPCs only exhibited increased Cx43 expression. In response to electrical stimulation, cardiac ATDPCs elongated, and both cardiac and subcutaneous ATDPCs became aligned following the linear surface pattern of the construct. Cardiac ATDPC length increased by 11.3%, while subcutaneous ATDPC length diminished by 11.2% (p = 0.013 and p = 0.030 vs unstimulated controls, respectively). Compared to controls, electrostimulated cells became aligned better to the patterned surfaces when the pattern was perpendicular to the electric field (89.71 ± 28.47º for cardiac ATDPCs and 92.15 ± 15.21º for subcutaneous ATDPCs). Electrical stimulation of cardiac ATDPCs caused changes in cell phenotype and genetic machinery, making them more suitable for cardiac regeneration approaches. Thus, it seems advisable to use electrical cell training before delivery as a cell suspension or within engineered tissue

Cardiac tissue engineering by electrical stimulation with subcutaneous and cardiac adipose-tissue derived progenitor cells (ATDPCs)

A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. In native heart, pacing cells generate electrical stimuli that spread throughout the heart causing cell membrane depolarization and activation of contractile apparatus. We ought to examine whether electrical stimulation of adipose tissue-derived progenitor cells (ATDPCs) exerts phenotypic and genetic changes that enhance their cardiomyogenic potential.Peer ReviewedPostprint (published version

Towards on line monitoring the evolution of the myocardium infarction scar with an implantable electrical impedance spectrum monitoring system.

The human heart tissue has a limited capacity for regeneration. Tissue and cellular therapies based on the use of stem cells may be useful alternatives to limit the size of myocardial infarction. In this paper, the preliminary results from an experimental campaign for on-line monitoring of myocardium scar infarction are presented. This study has been carried out under a research project that has as main objective the development and application of a bioactive patch implant for regeneration of myocardial infarction. Electrical Impedance Spectroscopy (EIS) has been chosen as a tissue state monitoring technique. What is presented in this communication is the first results of an implantable EIS measurement system which has been implanted in a subset of the animals corresponding to the control group, along one month. In all the animals, the myocardial infarction was induced by the ligation of the first circumflex marginal artery. In the animal group presented,the bioactive patch scaffold and the electrodes were implanted without the stem cells load. The scaffold is a piece of decellularized human pericardium, lyophilized and rehydrated with hydrogel RAD16-I. Nanogold particles were also placed near the electrodes to improve the electrode area conductivity. The results presented correspond to the subset of animals (n = 5), which had implanted the bioimpedance system monitoring the electrical impedance spectrum in vivo during 1 month. Two electrodes were connected to the bioactive patch implant. A total of 14 logarithmically spaced frequencies were measured every 5 minutes, from 100 Hz to 200 kHz. Results show a convergence of low-frequency and high frequency impedance magnitudes along the measurement period, which is coherent with the scar formation

Cardiac tissue engineering by electrical stimulation with subcutaneous and cardiac adipose-tissue derived progenitor cells (ATDPCs)

A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. In native heart, pacing cells generate electrical stimuli that spread throughout the heart causing cell membrane depolarization and activation of contractile apparatus. We ought to examine whether electrical stimulation of adipose tissue-derived progenitor cells (ATDPCs) exerts phenotypic and genetic changes that enhance their cardiomyogenic potential.Peer Reviewe

Mesenchymal stem cells for cardiac repair: are the actors ready for the clinical scenario?

Abstract For years, sufficient progress has been made in treating heart failure following myocardial infarction; however, the social and economic burdens and the costs to world health systems remain high. Moreover, treatment advances have not resolved the underlying problem of functional heart tissue loss. In this field of research, for years we have actively explored innovative biotherapies for cardiac repair. Here, we present a general, critical overview of our experience in using mesenchymal stem cells, derived from cardiac adipose tissue and umbilical cord blood, in a variety of cell therapy and tissue engineering approaches. We also include the latest advances and future challenges, including good manufacturing practice and regulatory issues. Finally, we evaluate whether recent approaches hold potential for reliable translation to clinical trials