Department of Pathology, University of Cincinnati, Cincinnati, OH 45267-0529, USA.
Regen Med. 2011 Mar;6(2):171-8. doi: 10.2217/rme.10.103.
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.
METHODS & RESULTS: 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 × 10(5) 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.
通过将干性基因遗传重编程体细胞来恢复其多能性状态，从而产生多能干细胞来替代胚胎干细胞，这一研究正在广泛开展。本研究旨在探讨年轻雄性 Oct4/GFP 转基因小鼠骨骼肌成肌细胞衍生的诱导多能干细胞（SkiPS）在梗死心脏再生中的有效性。
在年轻的雌性免疫功能正常的 C57BL/6J 或 C57BL/6x129S4 SV/jae Oct4/GFP 小鼠中建立了永久性冠状动脉结扎的小鼠模型。在冠状动脉结扎后（n = 16）直视下将 Q-dots 标记的 SkiPS（10 µl 基础 Dulbecco 改良 Eagle 培养基中 3×10(5)个）移植到梗死区及其周围。对照组（n = 12）注射了相同数量的骨骼肌成肌细胞。组织学研究证明，4 周后所有存活动物的 SkiPS 均成功植入。然而，在 16 只 SkiPS 移植的动物心脏中有 6 只（37.5%）出现了壁内畸胎瘤，而对照组动物未观察到肿瘤生长。也在肿瘤部位观察到了 Q-dot 标记的供体细胞。组织学研究显示，畸胎瘤由三个胚层的细胞组成。超微结构研究证实了组织学发现，并显示肿瘤中有组织结构良好的肌原纤维区域。
除非对未分化的诱导多能干细胞进行特定的致畸前体筛查或在移植前预先分化为心脏谱系，否则不建议将其用于心脏移植。
