Tubular Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells Generate Pulse Pressure In Vivo

Human induced pluripotent stem (iPS) cell-derived cardiac cells provide the possibility to fabricate cardiac tissues for transplantation. However, it remains unclear human bioengineered cardiac tissues function as a functional pump in vivo. Human iPS cells induced to cardiomyocytes in suspension were cultured on temperature-responsive dishes to fabricate cardiac cell sheets. Two pairs of triple-layered sheets were transplanted to wrap around the inferior vena cava (IVC) of nude rats. At 4 weeks after transplantation, inner pressure changes in the IVC were synchronized with electrical activations of the graft. Under 80 pulses per minute electrical stimulation, the inner pressure changes at 8 weeks increased to 9.1 ± 3.2 mmHg, which were accompanied by increases in the baseline inner pressure of the IVC. Immunohistochemical analysis revealed that 0.5-mm-thick cardiac troponin T-positive cardiac tissues, which contained abundant human mitochondria, were clearly engrafted lamellar around the IVC and surrounded by von Willebrand factor-positive capillary vessels. The mRNA expression of several contractile proteins in cardiac tissues at 8 weeks in vivo was significantly upregulated compared with those at 4 weeks. We succeeded in generating pulse pressure by tubular human cardiac tissues in vivo. This technology might lead to the development of a bioengineered heart assist pump.