How do we compose mature organoids in vitro - Characterization of organ-specific extracellular matrix and potential of collagen originated from the heart in pig

Abstract

Although the extracellular matrix (ECM) plays essential roles in heart tissue engineering, the optimal ECM components for heart tissue organization have not previously been elucidated, and most of the commercially available collagen is skin-derived and type I collagen. Here, we focused on the main ECM component, fibrillar collagen, and analyzed the effects of collagens on heart tissue engineering, by comparing the use of porcine heart-derived collagen and other organ organs (kidney, liver, lung, skin, and spleen) derived collagens in generating engineered heart tissue (EHT). We demonstrate that heart-derived collagen induces better contraction and relaxation of human-induced pluripotent stem cell-derived EHT (hiPSC-EHT) and that hiPSC-EHT with heart-derived collagen exhibit more mature profiles than those with collagens from other organs. Further, we found that collagen fibril formation and gel stiffness influence the contraction, relaxation, and maturation of hiPSC-EHT, suggesting the importance of collagen types III and type V, which are relatively abundant in the heart. Furthermore, mRNA expression related to maturation was highest in EHTs with crude collagen compared with EHTs with purified type collagen, indicating that the component of each type of collagen in the appropriate distribution has significant effects on tissue maturation. Thus, we demonstrated the potency of heart-derived collagen in heart tissue engineering and drug discovery.