Development of Bioartificial Myocardium by Electrostimulation of 3D Collagen Scaffolds Seeded with Stem Cells

Abstract

Electrostimulation (ES) can be defined as a safe physical method to induce stem cell differentiation. The aim of this study is to evaluate the effectiveness of ES on bone marrow mesenchymal stem cells (BMSCs) seeded in collagen scaffolds in terms of proliferation and differentiation into cardiomyocytes. BMSCs were isolated from Wistar rats and seeded into 3D collagen type 1 templates measuring 25 × 25 × 6 mm. Bipolar in vitro ES was performed during 21 days. Electrical impedance and cell proliferation were measured. Expression of cardiac markers was assessed by immunocytochemistry. Viscoelasticity of collagen matrix was evaluated. Electrical impedance assessments showed a low resistance of 234±41 Ohms which indicates good electrical conductivity of collagen matrix. Cell proliferation at 570 nm as significantly increased in ES groups after seven day (ES 0.129±0.03 vs non-stimulated control matrix 0.06±0.01, P=0.002) and after 21 days, (ES 0.22±0.04 vs control 0.13±0.01, P=0.01). Immunocytoche mistry of BMSCs after 21 days ES showed positive staining of cardiac markers, troponin I, connexin 43, sarcomeric alpha-actinin, slow myosin, fast myosin and desmin. Staining for BMSCs marker CD29 after 21 days was negative. Electrostimulation of cell-seeded collagen matrix changed stem cell morphology and biochemical characteristics, increasing the expression of cardiac markers. Thus, MSC-derived differentiated cells by electrostimulation grafted in biological scaffolds might result in a convenient tissue engineering source for myocardial diseases.

Porous nanofibrous poly(l-lactic acid) scaffolds supporting cardiovascular progenitor cells for cardiac tissue engineering

“…7). Thus, the host tissue invasion and the interactions between the grafted cells and the host cells likely facilitated the angiogenesis in the constructs in vivo, probably via mechanisms involving paracrine secretion of growth factors and cytokines [56]. Further studies are needed to confirm and elucidate the underlying mechanisms.…”

“…We are adjusting the molecular size of the PLLA to have its degradation rate match the regeneration of cardiac tissue with the seeded cells and the integration of the constructs with the host tissue. Moreover, electrical [56, 57] and mechanical [58, 59] stimuli have been reported to facilitate cardiac differentiation and cardiac tissue organization. Thus, both rhythmic electrical and mechanical stimuli will be utilized in the construction of cardiac tissue in our future studies.…”

Three dimensionalde novomicro bone marrow and its versatile application in drug screening and regenerative medicine

“…This research points out that 3D scaffolds could be valuable in regeneration of cardiomyocytes from patients suffering from myocardial infarction. 81 …”

Creating the bioartificial myocardium for cardiac repair: challenges and clinical targets

“…Experimental studies demonstrated that electrostimulation of cell-seeded collagen matrix changed stem cell morphology and biochemical characteristics, increasing the expression of cardiac markers [32,33]. This preconditioned biological matrix scaffold could be useful for myocardial support and regeneration [102].…”