Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells
Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells
复制标题
DOI：
10.1002/term.1995
复制
发表时间：
2017-03-01
影响因子：
3.3
通讯作者：
Shimizu, Tatsuya
中科院分区：
文献类型：
--
作者：
Komae, Hyoe;Sekine, Hidekazu;Shimizu, Tatsuya
目前治疗严重心力衰竭最根本的方法是心脏移植；然而，捐献心脏的数量是有限的。更好的方法是制造人类心脏组织。我们开发了一种原始的基于细胞片的组织工程技术，通过分层心肌细胞片来制造人类心脏组织。将人诱导多能干细胞分化为心肌细胞，制备心肌细胞片。首先，将三层人iPS心肌细胞（hiPSCM）薄片移植到裸鼠皮下组织。接下来，为了制造更厚的组织，在一天内移植三层薄片，然后在第一层薄片血管化后，第二天再移植另外三层薄片。在第3天，再次移植最后的三层薄片，形成九层移植物（多步骤移植程序）。最后一步，将6层薄片移植到腹股沟部分脂肪组织上，与股动脉、股静脉一起切除，制成血管可连通的可移植移植物。然后通过将血管与宿主颈动脉和静脉吻合，将它们移植到其他大鼠的颈部。移植的三层hiPSCMs有搏动，组织学上显示心肌样结构，有血管系统。此外，移植的hipscs在体内增殖和成熟。通过多步骤的移植程序，制备了明显较厚的组织。异位移植的移植物存活下来并继续搏动。我们成功地利用细胞片技术制造了具有功能的人类心脏组织。移植这种心脏组织可能成为严重心力衰竭的一种新的治疗选择。版权所有：John Wiley & Sons， Ltd
The most radical treatment currently available for severe heart failure is heart transplantation; however, the number of donor hearts is limited. A better approach is to make human cardiac tissues. We developed an original cell sheet-based tissue-engineering technology to fabricate human cardiac tissue by layering myocardial cell sheets. Human induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes to fabricate cardiomyocyte sheets. Initially, three-layer human iPS cardiomyocyte (hiPSCM) sheets were transplanted on subcutaneous tissues of nude rats. Next, to fabricate thicker tissue, three-layer sheets were transplanted on one day, then additional three-layer sheets were transplanted onto them the following day, after the first sheets were vascularized. On day 3, the final three-layer sheets were again transplanted, creating a nine-layer graft (multi- step transplantation procedure). In the last step, six-layer sheets were transplanted on fat tissues of the inguinal portion, which were subsequently resected together with the femoral arteries and veins to make transplantable grafts with connectable vessels. They were then transplanted ectopicallyto the neck portion of other rats by anastomosing vessels with the host's jugular arteries and veins. Transplanted three-layer hiPSCMs were beating and, histologically, showed a cardiac muscle-like structure with vascular systems. Moreover, transplanted hiPSCMs proliferated and matured in vivo. Significantly thicker tissues were fabricated by a multi- step transplantation procedure. The ectopically transplanted graft survived and continued to beat. We succeeded in fabricating functional human cardiac tissue with cell sheet technology. Transplanting this cardiac tissue may become a new treatment option for severe heart failure. Copyright (c) 2015 John Wiley & Sons, Ltd.