Biofabrication of Injectable Stem Cell-laden Spheroids for the Treatment of Ischemic Heart Diseases

Abstract

Ischemic heart disease remains the leading cause of death in worldwide for several decades. It is classified as an incurable disease due to the limited regenerative capability of the ischemic tissues. Although stem cell therapy has emerged to overcome this disease, it has limitation about low rate of adhesion and differentiation of transplanted cells. In this study, three-dimensional spheroids including human c-kit+ mesenchymal stem cells and endothelial progenitor cells were fabricated by using 3D bioprinting technique. Bioink, mixture of heart decellularized extracellular matrix (hdECM), stem cells, and alginate, was prepared and was dropped and cross linked in a dish which is containing calcium chloride in a programmed manner. Optimal composition ratios were found by varying the composition of the materials to be mixed, and various sizes of spheroids were produced by changing the parameters such as pneumatic pressure, pressure time, and nozzle size. Also, predominant green fluorescence evidenced dominated population of live cells and clearly indicates that cells were viable and environment in the spheroid was biocompatible niche condition. It is expected that this can be used in the future to prevent or treat heart-related diseases.