Developing Thick Cardiac Tissue with a Multilayer Fiber Sheet for Treating Myocardial Infarction

Abstract

Human-induced pluripotent stem cell (hiPSC)-derived cardiac patches have been extensively used for treating myocardial infarction and have shown potential for clinical application. However, the limited patch thickness can hamper its therapeutic effect. We previously developed a fibrous scaffold that allowed the formation of well-organized cardiac tissue constructs. In the present study, based on the above technology, we developed a three-dimensional multilayer fibrous scaffold with dynamic perfusion, on which approximately 20 million hiPSC-derived cardiomyocytes (CMs) could be seeded in a single step and organized into 1 mm thick and viable tissue. The multilayer cardiac tissue demonstrated enhanced contractile properties and upregulated cytokine secretion compared with the control group. Notably, when used on the myocardial infarction model, the multilayer group showed improved functional recovery and less fibrosis. These results indicated that the appropriate hiPSC-CM dose requires careful evaluation in developing clinical therapy. The multilayer cardiac tissue group demonstrated significant improvement than the control group, indicating that higher doses of transplanted cells may have improved therapeutic effects in treating myocardial infarction.

Funding

Japan Society for the Promotion of Science London(Japan Society for the Promotion of Science London); Osaka University