Department of Cardiology, Japan; Joint Research Laboratory for Medical Innovation in Heart Disease, Japan.
Department of Organ Fabrication, Japan; Department of Kidney Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Biomaterials. 2023 Aug;299:122174. doi: 10.1016/j.biomaterials.2023.122174. Epub 2023 May 29.
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. 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-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. Thus, we demonstrate the effectiveness of organ-specific collagens in tissue engineering and drug discovery.
尽管细胞外基质 (ECM) 在心脏组织工程中发挥着重要作用，但对于心脏组织构建的最佳 ECM 成分，目前仍未阐明。在这里，我们专注于 ECM 的主要成分纤维状胶原，并通过比较猪心来源的胶原和其他器官来源的胶原在生成工程心脏组织 (EHT) 方面的应用，来分析胶原的作用。我们证明，心脏来源的胶原可诱导人诱导多能干细胞衍生的 EHT（hiPSC-EHT）更好地收缩和舒张，且具有心脏来源胶原的 hiPSC-EHT 比具有其他器官来源胶原的 hiPSC-EHT 表现出更成熟的特征。此外，我们发现胶原纤维的形成和凝胶硬度会影响 hiPSC-EHT 的收缩、舒张和成熟，提示心脏中相对丰富的胶原 III 型和 V 型的重要性。因此，我们证明了器官特异性胶原在组织工程和药物发现中的有效性。
