Department of Cardiovascular Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
Sci Rep. 2017 Mar 30;7:45499. doi: 10.1038/srep45499.
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.
人诱导多能干细胞（iPS）衍生的心肌细胞为移植制造心肌组织提供了可能性。然而，人生物工程化的心肌组织在体内是否能作为功能性泵发挥作用仍不清楚。将悬浮培养的人 iPS 细胞诱导为心肌细胞，然后在温度响应培养皿上培养以制造心肌细胞片。将两对三层片移植到裸鼠的下腔静脉（IVC）周围。移植后 4 周，IVC 内的压力变化与移植物的电激活同步。在 80 次/分钟的电刺激下，第 8 周时 IVC 的压力变化增加到 9.1±3.2mmHg，同时 IVC 的基础内压也增加。免疫组织化学分析显示，厚 0.5 毫米的心肌肌钙蛋白 T 阳性心肌组织中含有丰富的人线粒体，明显地移植到 IVC 周围，并被 von Willebrand 因子阳性的毛细血管包围。与第 4 周相比，体内第 8 周的心肌组织中几种收缩蛋白的 mRNA 表达明显上调。我们成功地在体内产生了管状人心肌组织的搏动压力。这项技术可能会促进生物工程心脏辅助泵的发展。
