Tokyo Women's Medical University confirmed alignment-controlled cardiomyocyte showed improved contractile and relaxation properties of the entire tissue

A research group of Tokyo Women's Medical University, including Takuma Takada, student of the Graduate School of Medicine, Department of Cardiology, Assistant Professor Daisuke Sasaki of the Institute of Advanced Biomedical Engineering and Science, and Associate Professor Katsuhisa Matsuura succeeded in fabricating human cardiac muscle tissue with controlled alignment and found that the cardiomyocyte in the cardiac muscle tissue would contract and relax unidirectionally and that facilitating synchronized contraction improves contractile and relaxation properties of the entire tissue.

Cardiomyocytes will not align just through cultivation on a culture plate alone. It is also difficult to evaluate the contractile and relaxation functions of the tissue if it is just cultivated on a plastic culture plate. The research group have achieved the evaluation of contractile and relaxation properties of cardiac muscle tissue through culturing cardiac muscle on fibrin gel and using a unique tensile measurement system. The group decided to evaluate the relationship between alignment and contractile and relaxation properties of cardiomyocyte by fabricating fibrin gel that enables the control of the alignment of the cells.

Using cyclo olefin polymer thermally imprinted on a micro-processed silicon wafer as a cast, polydimethylsilioxane with V-shaped grooves on the stripe was fabricated. Fibrin was applied on it to obtain micro-processed fibrin gel. When human iPS-induced cardiomyocyte was seeded on the micro-processed fibrin gel, alignment performance was improved significantly than when it was seeded on non-processed fibrin gel.

Next, the group examined the mechanism of improving contractile and relaxation properties of aligned cardiac muscle tissue. In regard to the expression of genes related to controlling contractile proteins and intracellular calcium regulation, and ion channels, there were no significant differences between aligned and non-aligned cardiac muscle tissue and so it was assumed that the involvement of maturation of individual cardiomyocytes was small. On the other hand, evaluation of direction and timing of contracting cardiomyocyte in cardiac muscle tissue using images revealed that, compared with non-aligned cardiac muscle tissue, aligned ones showed more unidirectional contraction, and that they contracted synchronously. This suggested that an appropriate environment was necessary for each cardiomyocyte to function in a coordinated manner, in order to improve the function of cardiac muscle tissue.

"The findings, I believe, will provide fundamental knowledge for fabricating more functional 3D cardiac muscle tissue, that is needed for reproductive medicine and the R&D of diseases and drugs. As disorganized cardiomyocyte alignment is shown in various cardiac disorders, it is expected that in the future, the relationship between disorganized alignment of cardiomyocyte, contractile and relaxation property disorders and arrhythmogenic effects will be clarified," commented Associate Professor Matsuura.