The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to mscs

Autor: Georgina Shaw, Valerie Barron, Frank Barry, Eoin D. O'Cearbhaill, Joseph N. Mackle, Werner J. Blau, David Blond, Emma Mooney, J. Mary Murphy
Rok vydání: 2012
Předmět:
Materials science
Cell
microstructure
Biophysics
mesenchymal stem-cells
cardiac differentiation
Bioengineering
Stimulation
cardiomyocyte
cardiomyocytes
Cardiomyocyte
heart
Biomaterials
electroactive polymer
paracrine mechanisms
Nanoparticle
Downregulation and upregulation
Western blot
medicine
Humans
Myocytes
Cardiac
electrical stimulation
Electroactive polymer
Cells
Cultured
mesenchymal stem cell
fields
Mesenchymal stem cell
Tissue Engineering
medicine.diagnostic_test
electrospun composite nanofibers
Nanotubes
Carbon
Regeneration (biology)
carbon
nanoparticle
Cardiac muscle
Cell Differentiation
Mesenchymal Stem Cells
electrostimulation
gene-expression
Carbon
Electric Stimulation
Cell biology
Electrophysiology
medicine.anatomical_structure
Mechanics of Materials
Electrical stimulation
Ceramics and Composites
Biomedical engineering
Popis: Once damaged, cardiac muscle has little intrinsic repair capability due to the poor regeneration potential of remaining cardiomyocytes. One method of overcoming this issue is to deliver functional cells to the injured myocardium to promote repair. To address this limitation we sought to test the hypothesis that electroactive carbon nanotubes (CNT) could be employed to direct mesenchymal stem cell (MSC) differentiation towards a cardiomyocyte lineage. Using a two-pronged approach, MSCs exposed to medium containing CNT and MSCs seeded on CNT based polylactic acid scaffolds were electrically stimulated in an electrophysiological bioreactor. After electrical stimulation the cells reoriented perpendicular to the direction of the current and adopted an elongated morphology. Using qPCR, an upregulation in a range of cardiac markers was detected, the greatest of which was observed for cardiac myosin heavy chain (CMHC), where a 40-fold increase was observed for the electrically stimulated cells after 14 days, and a 12-fold increase was observed for the electrically stimulated cells seeded on the PLA scaffolds after 10 days. Differentiation towards a cardioprogenitor cell was more evident from the western blot analysis, where upregulation of Nkx2.5, GATA-4, cardiac troponin t (CTT) and connexin43 (C43) was seen to occur. This was echoed in immunofluorescent staining, where increased levels of CTT, CMHC and C43 protein expression were observed after electrical stimulation for both cells and cell-seeded scaffolds. More interestingly, there was evidence of increased cross talk between the cells as shown by the pattern of C43 staining after electrical stimulation. These results establish a paradigm for nanoscale biomimetic cues that can be readily translated to other electroactive tissue repair applications. Science Foundation Ireland under the Research Frontiers Programme award no. RFP/05/ENG004, REMEDI CSET award no. 08/CE/B1436 and REMEDI SRC, award no. 09/SRC/B1794. Deposited by bulk import
Databáze: OpenAIRE
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