Cardiac tumorigenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction.
Cardiac tumorigenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction.
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DOI：
10.2217/rme.10.103
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发表时间：
2011-03
影响因子：
2.7
通讯作者：
Haider HKh
中科院分区：
文献类型：
--
作者：
Ahmed RP;Ashraf M;Buccini S;Shujia J;Haider HKh
通过对具有干细胞基因的体细胞进行基因重编程，使其恢复多能状态，从而产生多能干细胞作为胚胎干细胞的替代品，目前已被广泛研究。本研究旨在检测来自年轻雄性Oct4/GFP转基因小鼠的成骨肌细胞衍生的诱导多能干细胞（SkiPS）对梗死心脏再生的有效性。以年轻雌性C57BL/6J或C57BL/6x129S4 SV/jae Oct4/GFP小鼠为实验对象，建立永久性冠状动脉结扎小鼠模型。冠状动脉结扎后立即在目视下将q点标记的SkiPS （3 × 105, 10 μl基础Dulbecco改良Eagle培养基）移植到梗死区域内和周围（n = 16）。对照小鼠（n = 12）注射相同数量的成骨骼肌细胞。组织学研究表明，4周后所有存活的动物都成功植入了SkiPS。然而，16个skip移植的动物心脏中有6个（37.5%）显示畸胎瘤，而对照组小鼠未观察到肿瘤生长。在肿瘤部位也观察到q点标记的供体细胞。组织学研究表明畸胎瘤是由来自所有三个胚胎胚层的细胞组成的。超微结构研究证实了组织学上的发现，并显示肿瘤中有组织良好的肌原纤维结构。未分化的诱导多能干细胞不应推荐用于心脏移植，除非在移植前筛选特定的致畸前体或预分化成心脏谱系。
Genetic reprogramming of somatic cells with stemness genes to restore their pluripotent status is being studied extensively to generate pluripotent stem cells as an alternative to embryonic stem cells. This study was designed to examine the effectiveness of skeletal myoblast-derived induced pluripotent stem cells (SkiPS) from young male Oct4/GFP transgenic mice for regeneration of the infarcted heart. A mouse model of permanent coronary artery ligation was developed in young female immunocompetent C57BL/6J or C57BL/6x129S4 SV/jae Oct4/GFP mice. SkiPS labeled with Q-dots (3 × 105 in 10 μl basal Dulbecco’s modified Eagle’s medium) were transplanted in and around the area of infarct immediately after coronary artery ligation (n = 16) under direct vision. Control mice (n = 12) were injected with the same number of skeletal myoblasts. Histological studies documented successful engraftment of SkiPS in all the surviving animals 4 weeks later. However, six of the 16 SkiPS-transplanted (37.5%) animal hearts showed intramural teratomas, whereas no tumor growth was observed in the control mice. Q-dot-labeled donor cells were also observed at the site of tumors. Histological studies revealed that teratomas were composed of cells from all of the three embryonic germ layers. Ultra-structure studies confirmed the histological findings and showed regions with well-organized myofibrillar structures in the tumors. Undifferentiated induced pluripotent stem cells should not be recommended for cardiac transplantation unless screened for specific teratogenic precursors or predifferentiated into cardiac lineage prior to transplantation.