In vivo molecular MRI of cell survival and teratoma formation following embryonic stem cell transplantation into the injured murine myocardium.

In vivo molecular MRI of cell survival and teratoma formation following embryonic stem cell transplantation into the injured murine myocardium.
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DOI:
10.1002/mrm.22929
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发表时间:
2011-11
影响因子:
3.3
通讯作者:
Yang, Phillip C.
Yang, Phillip C.
中科院分区:
医学3区
文献类型:
--
作者:
Chung, Jaehoon;Kee, Kehkooi;Barral, Joelle K.;Dash, Rajesh;Kosuge, Hisanori;Wang, Xi;Weissman, Irving;Robbins, Robert C.;Nishimura, Dwight;Quertermous, Thomas;Reijo-Pera, Renee A.;Yang, Phillip C.

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胚胎干细胞(ESCs)已显示出在心肌损伤后恢复心脏功能的潜力。超顺磁性氧化铁纳米颗粒(SPIO)已被广泛应用于细胞磁共振标记ESCs。然而,SPIO在细胞内的非特异性积聚限制了对移植细胞的长期体内评估。为了克服这一局限性,一种新的报告基因(RG)被开发出来,用于在ESC表面表达抗原。通过使用SPIO标记的抗这些抗原的单抗(SPIO-MAb),可以在体内检测移植的ESCs的活性。本研究旨在开发一种新的分子磁共振方法来评估体内胚胎干细胞的活性、增殖和畸胎瘤的形成。RG的设计目的是在ESC表面表达两种抗原(血凝素A和myc)和荧光素酶。这两种抗原是SPIO-MAb的分子靶点。用RG(ESC-RGS)转导人和小鼠ESCs,并用小鼠心肌损伤模型将其移植到梗死区。连续静脉注射SPIO-MAb后进行体内MRI检查。存活和增殖的ESCs和随后的畸胎瘤产生明显的低信号。这项新的分子磁共振技术能够在体内检测受损小鼠心肌中ESC来源的早期畸胎瘤的形成。
Embryonic stem cells (ESCs) have shown the potential to restore cardiac function after myocardial injury. Superparamagnetic iron oxide nanoparticles (SPIO) have been widely employed to label ESCs for cellular MRI. However, non-specific intracellular accumulation of SPIO limits long-term in vivo assessment of the transplanted cells. To overcome this limitation, a novel reporter gene (RG) has been developed to express antigens on the ESC surface. By employing SPIO-conjugated monoclonal antibody against these antigens (SPIO-MAb), the viability of transplanted ESCs can be detected in vivo. This study aims to develop a new molecular MRI method to assess in vivo ESC viability, proliferation, and teratoma formation. The RG is designed to express 2 antigens (hemagglutinin A and myc) and luciferase on the ESC surface. The two antigens serve as the molecular targets for SPIO-MAb. The human and mouse ESCs were transduced with the RG (ESC-RGs) and transplanted into the peri-infarct area using the murine myocardial injury model. In vivo MRI was performed following serial intravenous administration of SPIO-MAb. Significant hypointense signal was generated from the viable and proliferating ESCs and subsequent teratoma. This novel molecular MRI technique enabled in vivo detection of early ESC-derived teratoma formation in the injured murine myocardium.
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