2023/06/20
Keio University School of Medicine
A research group led by Senior Lecturer Shugo Tohyama and Guest Professor Eiji Kobayashi of the Division of Cardiology, Department of Internal Medicine, Keio University School of Medicine, and Project Assistant Professor Hidenori Tani of the Joint Research Program for Future Cardiac Therapeutics, School of Medicine and Graduate School of Medicine, has successfully created mature human engineered heart tissue by using collagen extracted from porcine hearts in a joint research project with Nippi, Inc.
Human induced pluripotent stem (iPS) cells can be differentiated into cardiomyocytes because they are pluripotent, meaning they can theoretically differentiate into all cell types that make up the body. Therefore, they are expected to be applied to disease and drug discovery research by enabling the mass production of cardiomyocytes, a resource that has traditionally been limited, and by creating cardiomyocytes with patient-specific characteristics, such as hereditary traits, in culture dishes. However, a major challenge is that human iPS cell-derived cardiomyocytes created in culture dishes are immature cells, equivalent to those in the fetal stage, and the reproducibility of their maturation for use in such research is insufficient.
This time, the joint research group focused on the organ-specific differences in fibrillar collagen, the most important component of the extracellular matrix. As a result, they confirmed that when creating human engineered heart tissue, adding collagens extracted from six different porcine organs (heart, spleen, kidney, liver, lung, and skin), the human engineered heart tissue using heart collagen was the most stable in shape and showed the most advanced maturation both structurally and functionally. They found that the reason for this difference lies in the composition of the collagen, and that a high content of type III and type V collagen, in addition to type I, is crucial for both maintaining the shape of human heart tissue, which constantly contracts and relaxes, and for the maturation of the tissue. This research is expected to yield more useful results in future drug discovery and disease model research, and it is believed to have generated new knowledge that organ-specific extracellular matrices are involved in the maturation of the cells that constitute that organ.
The results of this research were published in the international academic journal Biomaterials on May 29, 2023 (US Eastern Time).
For the full press release, please see below.