Noninvasive Detection of Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Teratoma with an Integrin-Targeting Agent 99mTc-3PRGD2
Noninvasive Detection of Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Teratoma with an Integrin-Targeting Agent 99mTc-3PRGD2
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使用整合素靶向剂 99mTc-3PRGD2 无创检测人诱导多能干细胞 (hiPSC) 衍生的畸胎瘤
DOI：
10.1007/s11307-012-0571-1
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
李扬
中科院分区：
文献类型：
--
作者：
李扬
目的自 2006 年发现以来，诱导多能干细胞 (iPSC) 在组织再生和移植治疗方面引起了越来越多的兴趣。然而，iPSC移植后畸胎瘤的形成是最严重的缺点之一，可能限制其进一步的临床应用。我们在这里研究了是否可以通过整联蛋白靶向剂 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) 检测人类 iPSC 衍生的畸胎瘤。方法生成并表征人类诱导的多能干细胞 (hiPSC)。通过流式细胞术测定 hiPSC 和 hiPSC 衍生畸胎瘤细胞的体外整合素 αvβ3 表达水平。制备了 99mTc-3PRGD2，并在患有畸胎瘤的严重联合免疫缺陷（SCID）小鼠中进行了平面伽马成像和生物分布研究。还使用 2-脱氧-2-[18F]氟-d-葡萄糖 (18F-FDG) 对畸胎瘤进行正电子发射断层扫描 (PET) 成像以进行比较。通过免疫荧光染色测定畸胎瘤组织中整合素αvβ3的表达。结果99mTc-3PRGD2表现出高（感染后0.5和1小时分别为2.82±±0.21和2.69±±0.73％ID/g）和特异性（畸胎瘤摄取从2.69±0.73下降到用冷3PRGD2)封闭后畸胎瘤组织的摄取为0.53±0.26%ID/g，平面伽马成像证明了用99mTc-3PRGD2无创检测畸胎瘤形成的可行性。 18F-FDG 显示畸胎瘤摄取较低，因此未能检测到畸胎瘤。离体免疫荧光染色验证了畸胎瘤形成过程中脉管系统中整合素αvβ3的表达。结论99mTc-3PRGD2伽马成像是一种有前途的hiPSC移植后致瘤性监测的无创方法。
PurposeSince their discovery in 2006, induced pluripotent stem cells (iPSCs) have gained increasing interest for tissue regeneration and transplantation therapies. However, teratoma formation after iPSC transplantation is one of the most serious drawbacks that may limit their further clinical application. We investigated here whether human iPSC-derived teratomas could be detected by an integrin-targeting agent 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2).MethodsHuman-induced pluripotent stem cells (hiPSCs) were generated and characterized. In vitro integrin αvβ3 expression levels of hiPSC- and hiPSC-derived teratoma cells were determined by flow cytometry. 99mTc-3PRGD2 was prepared, and planar gamma imaging and biodistribution studies were carried out in teratoma-bearing severe combined immunodeficient (SCID) mice. Positron emission tomography (PET) imaging of teratomas with 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) was also performed for comparison. Integrin αvβ3 expression in teratoma tissues was determined by immunofluorescence staining.Results99mTc-3PRGD2 showed high (2.82 ± 0.21 and 2.69 ± 0.73%ID/g at 0.5 and 1 h pi, respectively) and specific (teratoma uptake decreased from 2.69 ± 0.73 to 0.53 ± 0.26%ID/g after blocking with cold 3PRGD2) uptake in teratoma tissues, and planar gamma imaging demonstrated the feasibility of noninvasively detecting the teratoma formation with 99mTc-3PRGD2. 18F-FDG showed low teratoma uptake and thus failed to detect the teratomas. Ex vivo immunofluorescence staining validated the integrin αvβ3 expression in the vasculature during teratoma formation.ConclusionGamma imaging with 99mTc-3PRGD2 is a promising approach for the noninvasive monitoring of tumorigenicity after hiPSCs transplantation.
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影响因子：
11.2
作者：
Cao F;Li Z;Lee A;Liu Z;Chen K;Wang H;Cai W;Chen X;Wu JC
通讯作者：
Wu JC
影响因子：
2.1
作者：
L. J. Putra;N. Lawrentschuk;N. Lawrentschuk;Z. Ballok;A. Hannah;A. Poon;A. Tauro;I. Davis;I. Davis;R. Hicks;D. Bolton;A. Scott;A. Scott
通讯作者：
L. J. Putra;N. Lawrentschuk;N. Lawrentschuk;Z. Ballok;A. Hannah;A. Poon;A. Tauro;I. Davis;I. Davis;R. Hicks;D. Bolton;A. Scott;A. Scott
影响因子：
4.7
作者：
Liu S
通讯作者：
Liu S
影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
DOI：
10.1016/s0093-3619(08)70915-8
发表时间：
2008
期刊：
Yearbook of Dermatology and Dermatologic Surgery
影响因子：
--
作者：
B. Thiers
通讯作者：
B. Thiers