Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts.
Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts.
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DOI：
10.1371/journal.pone.0201650
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Minatoya K
中科院分区：
文献类型：
--
作者：
Ishigami M;Masumoto H;Ikuno T;Aoki T;Kawatou M;Minakata K;Ikeda T;Sakata R;Yamashita JK;Minatoya K
为了实现基于人类诱导多能干细胞（hiPSC）的心脏再生疗法，在人类大小的患病心脏中的治疗优势的证据是不可或缺的。结合从hiPSC和细胞片技术中有效和同时分化各种心脏谱系，我们旨在产生临床尺寸的大心脏组织片（L-CTS）并评估猪梗死心脏的治疗潜力。我们同时从hiPSC诱导心肌细胞（CM）和血管细胞[血管内皮细胞（EC）和血管壁细胞（MC）]。我们使用10厘米大小的温度响应培养皿生成L-CTS。我们在微型猪（15-25 kg）中诱导心肌梗死（MI），并在MI诱导后2周在免疫抑制下移植L-CTS（Tx）（4片/受体）（Tx：n = 5，Sham：n = 5）。自搏动L-CTS直径约3.5cm，含有6.8×106±0.8个细胞，分别含有cTnT+-CM（45.6±13.2%）、VE-钙粘蛋白+-EC（5.3±4.4%）和PDGFRβ+-MC（14.4±20.7%）（n = 5）。在Tx组中，超声心动图显示与假手术对照相比，左心室（LV）的收缩功能显著更高（假手术vs Tx：缩短分数：24.2±8.6 vs 40.5±9.7%; p<0.05）。左室造影射血分数Tx组明显高于对照组（25.3± 6.2%vs39.8 ±4.2%，p<0.01）。斑点追踪超声心动图显示移植后梗死区和边缘区周向应变明显增加。Tx组纤维化面积明显低于对照组（23.8± 4.5vs15.9 ±3.8%; P<0.001）。Tx组中边缘区域中的毛细血管密度显著更高（75.9±42.6/mm 2对137.4±44.8/mm 2，p<0.001）。这些数据表明L-CTS移植减弱了LV重构。L-CTS潜在地恢复人类大小的梗死心脏的心功能障碍。
To realize human induced pluripotent stem cell (hiPSC)-based cardiac regenerative therapy, evidence of therapeutic advantages in human-sized diseased hearts are indispensable. In combination with an efficient and simultaneous differentiation of various cardiac lineages from hiPSCs and cell sheet technology, we aimed to generate clinical-sized large cardiac tissue sheets (L-CTSs) and to evaluate the therapeutic potential in porcine infarct heart. We simultaneously induced cardiomyocytes (CMs) and vascular cells [vascular endothelial cells (ECs) and vascular mural cells (MCs)] from hiPSCs. We generated L-CTSs using 10cm-sized temperature-responsive culture dishes. We induced myocardial infarction (MI) in micromini-pigs (15–25 kg) and transplanted the L-CTSs (Tx) 2 weeks after MI induction (4 sheets/recipient) under immunosuppression (Tx: n = 5, Sham: n = 5). Self-pulsating L-CTSs were approximately 3.5cm in diameter with 6.8×106±0.8 of cells containing cTnT+-CMs (45.6±13.2%), VE-cadherin+-ECs (5.3±4.4%) and PDGFRβ+-MCs (14.4±20.7%), respectively (n = 5). In Tx group, echocardiogram indicated a significantly higher systolic function of the left ventricle (LV) compared to that in sham control (Sham vs Tx: fractional shortening: 24.2±8.6 vs 40.5±9.7%; p<0.05). Ejection fraction evaluated by left ventriculogram was significantly higher in Tx group (25.3±6.2% vs 39.8±4.2%; p<0.01). Speckle tracking echocardiogram showed a significant increase of circumference strain in infarct and border regions after transplantation. Fibrotic area was significantly lower in Tx group (23.8±4.5 vs 15.9±3.8%; P<0.001). Capillary density in the border region was significantly higher in Tx group (75.9±42.6/mm2 vs 137.4±44.8/mm2, p<0.001). These data indicate that the L-CTS transplantation attenuated LV remodeling. L-CTSs potentially restore cardiac dysfunction of human-sized infarct heart.
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影响因子：
2.1
作者：
Galli A;Lombardi F
通讯作者：
Lombardi F
DOI：
10.1002/jbm.820271005
发表时间：
1993-10-01
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子：
--
作者：
OKANO, T;YAMADA, N;SAKURAI, Y
通讯作者：
SAKURAI, Y
影响因子：
2.1
作者：
Jung J;Kim YH;Kim N;Yang DH
通讯作者：
Yang DH
影响因子：
56.9
作者：
Thomson, JA;Itskovitz-Eldor, J;Jones, JM
通讯作者：
Jones, JM
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Tanabe, Koji;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya