The tumourigenicity of iPS cells and their differentiated derivates.
The tumourigenicity of iPS cells and their differentiated derivates.
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iPS细胞及其分化衍生物的致瘤性
DOI：
10.1111/jcmm.12062
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发表时间：
2013-06
影响因子：
5.3
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Liu Z;Tang Y;Lü S;Zhou J;Du Z;Duan C;Li Z;Wang C
诱导多能干细胞（iPSC）为再生医学提供了一种有前景的种子细胞。然而，iPSC在移植后有可能形成畸胎瘤。因此，在临床应用之前，有必要评估iPSC及其所有分化衍生物的致瘤风险。在此，用由单体红色荧光蛋白（mRFP）和萤火虫荧光素酶（Fluc）组成的双报告基因转导小鼠iPSCs。将未分化的iPSCs、诱导分化产生的iPSC衍生物（iPSC - 衍生物）、iPSC衍生的心肌细胞（iPSC - CMs）皮下注射到裸鼠背部。在移植后第1、7、14和28天进行纵向非侵入性生物发光成像（BLI），以追踪移植细胞的存活和增殖情况。在第28天，处死小鼠并取出移植物以检测畸胎瘤的形成。结果表明，移植的iPSCs、iPSC - 衍生物和iPSC - CMs在受体中存活。iPSCs和iPSC - 衍生物在移植后都大量增殖，而在iPSC - CM移植的小鼠中仅观察到BLI信号略有增加。在第28天，在iPSCs和iPSC - 衍生物移植的小鼠中都检测到畸胎瘤，但在iPSC - CM移植的小鼠中未检测到。体外研究表明，在iPSC分化过程中多能细胞长期存在。此外，当这些细胞作为未分化的iPSCs在饲养层中传代时，它们会恢复类似iPSC的集落，这表明了分化的iPSC具有致瘤性的原因。我们的研究表明，在iPSCs用于治疗之前，除了进行谱系特异性分化外，还需要通过筛选排除致瘤细胞。
Induced pluripotent stem cell (iPSC) provides a promising seeding cell for regenerative medicine. However, iPSC has the potential to form teratomas after transplantation. Therefore, it is necessary to evaluate the tumorigenic risks of iPSC and all its differentiated derivates prior to use in a clinical setting. Here, murine iPSCs were transduced with dual reporter gene consisting of monomeric red fluorescent protein (mRFP) and firefly luciferase (Fluc). Undifferentiated iPSCs, iPSC derivates from induced differentiation (iPSC‐derivates), iPSC‐derivated cardiomyocyte (iPSC‐CMs) were subcutaneously injected into the back of nude mice. Non‐invasive bioluminescence imaging (BLI) was longitudinally performed at day 1, 7, 14 and 28 after transplantation to track the survival and proliferation of transplanted cells. At day 28, mice were killed and grafts were explanted to detect teratoma formation. The results demonstrated that transplanted iPSCs, iPSC‐derivates and iPSC‐CMs survived in receipts. Both iPSCs and iPSC‐derivates proliferated dramatically after transplantation, while only slight increase in BLI signals was observed in iPSC‐CM transplanted mice. At day 28, teratomas were detected in both iPSCs and iPSC‐derivates transplanted mice, but not in iPSC‐CM transplanted ones. In vitro study showed the long‐term existence of pluripotent cells during iPSC differentiation. Furthermore, when these cells were passaged in feeder layers as undifferentiated iPSCs, they would recover iPSC‐like colonies, indicating the cause for differentiated iPSC's tumourigenicity. Our study indicates that exclusion of tumorigenic cells by screening in addition to lineage‐specific differentiation is necessary prior to therapeutic use of iPSCs.
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影响因子：
64.5
作者：
Park IH;Arora N;Huo H;Maherali N;Ahfeldt T;Shimamura A;Lensch MW;Cowan C;Hochedlinger K;Daley GQ
通讯作者：
Daley GQ
影响因子：
24
作者：
Dai, Bo;Huang, Wei;Xu, Meifeng;Millard, Ronald W.;Gao, Mei Hua;Hammond, H. Kirk;Menick, Donald R.;Ashraf, Muhammad;Wang, Yigang
通讯作者：
Wang, Yigang
DOI：
10.1084/jem.20061469
发表时间：
2006-10-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolossov E;Bostani T;Roell W;Breitbach M;Pillekamp F;Nygren JM;Sasse P;Rubenchik O;Fries JW;Wenzel D;Geisen C;Xia Y;Lu Z;Duan Y;Kettenhofen R;Jovinge S;Bloch W;Bohlen H;Welz A;Hescheler J;Jacobsen SE;Fleischmann BK
通讯作者：
Fleischmann BK
影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
影响因子：
24
作者：
Caspi, Oren;Huber, Irit;Gepstein, Lior
通讯作者：
Gepstein, Lior