Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo.
Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo.
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DOI：
10.3389/fcvm.2021.806215
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发表时间：
2021
影响因子：
3.6
通讯作者：
Kobayashi E
中科院分区：
文献类型：
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作者：
Kawai Y;Tohyama S;Arai K;Tamura T;Soma Y;Fukuda K;Shimizu H;Nakayama K;Kobayashi E
使用人诱导多能干细胞（hiPSC）制造的工程化心脏组织（EHT）已被认为是心力衰竭情况下的潜在心脏组织替代物。在本研究中，我们创建了hiPSC衍生的心脏类器官（hiPSC-CO），由hiPSC衍生的心肌细胞、人脐静脉内皮细胞和人成纤维细胞组成。为了为患有先天性心脏病的患者生产跳动导管，我们使用hiPSC-CO和具有针阵列的生物3D打印构建了无支架管状EHT（T-EHT）。将生物3D打印的T-EHT切开并移植到NOG小鼠的腹主动脉和下腔静脉（IVC）周围。用网膜覆盖移植的T-EHT，并在手术完成后闭合腹部。此外，为了比较hiPSC-CO与T-EHT的功能，我们将前者移植到主动脉和IVC周围，并将其注射到小鼠背部的皮下组织中。在移植程序1个月后，我们观察到小鼠中T-EHT的跳动。在组织学分析中，与移植在主动脉周围或皮下组织中的hiPSC-CO相比，T-EHT显示出心肌的清晰条纹和血管化。基于这些结果，与hiPSC-CO相比，生物3D打印的T-EHT在体内表现出更好的成熟。因此，这些跳动的T-EHT可以为先天性心脏病患者形成管道，并且T-EHT移植可以在这种情况下形成治疗选择。
Engineered heart tissues (EHTs) that are fabricated using human induced pluripotent stem cells (hiPSCs) have been considered as potential cardiac tissue substitutes in case of heart failure. In the present study, we have created hiPSC-derived cardiac organoids (hiPSC-COs) comprised of hiPSC-derived cardiomyocytes, human umbilical vein endothelial cells, and human fibroblasts. To produce a beating conduit for patients suffering from congenital heart diseases, we constructed scaffold-free tubular EHTs (T-EHTs) using hiPSC-COs and bio-3D printing with needle arrays. The bio-3D printed T-EHTs were cut open and transplanted around the abdominal aorta as well as the inferior vena cava (IVC) of NOG mice. The transplanted T-EHTs were covered with the omentum, and the abdomen was closed after completion of the procedure. Additionally, to compare the functionality of hiPSC-COs with that of T-EHTs, we transplanted the former around the aorta and IVC as well as injecting them into the subcutaneous tissue on the back of the mice. After 1 m of the transplantation procedures, we observed the beating of the T-EHTs in the mice. In histological analysis, the T-EHTs showed clear striation of the myocardium and vascularization compared to hiPSC-COs transplanted around the aorta or in subcutaneous tissue. Based on these results, bio-3D-printed T-EHTs exhibited a better maturation in vivo as compared to the hiPSC-COs. Therefore, these beating T-EHTs may form conduits for congenital heart disease patients, and T-EHT transplantation can form a treatment option in such cases.