Nonviral delivery of siRNA into mesenchymal stem cells by a combination of ultrasound and microbubbles

Nonviral delivery of siRNA into mesenchymal stem cells by a combination of ultrasound and microbubbles
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DOI:
10.1016/j.jconrel.2008.09.088
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发表时间:
2009-01-19
影响因子:
10.8
通讯作者:
Nagaya, Noritoshi
Nagaya, Noritoshi
中科院分区:
医学1区
文献类型:
--
作者:
Otani, Kentaro;Yamahara, Kenichi;Nagaya, Noritoshi

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细胞疗法是再生医学的一种有前途的治疗策略。然而,由于移植细胞的寿命短、成活率低,其目前的功效还不够。据报道,转基因干细胞移植可以提高细胞疗法的功效。本研究的目的是阐明超声和微泡 (US-MB) 组合将小干扰 RNA (siRNA) 递送至间充质干细胞 (MSC) 的可行性。虽然US-MB处理后观察到细胞损伤,但使用荧光标记的siRNA测定的转染效率在US-MB后显着增加。此外,US-MB 在细胞内递送 10 号染色体上删除的磷酸酶和张力蛋白同源物 (PTEN) siRNA,导致 PTEN mRNA 表达显着降低,并激活 Akt(生存信号通路的介质)。我们的结果表明 US-MB 可以作为 siRNA 进入 MSC 的非病毒递送方法。通过 US-MB 移植转基因 MSC 可能成为未来再生医学的一种有用策略。 (C) 2008 Elsevier B.V. 保留所有权利。
Cell therapy is a promising therapeutic strategy for regenerative medicine. However, its current efficacy is insufficient, because of the short lifetime and low engraftment of transplanted cells. Transplantation of genetically modified stem cells has been reported to improve the efficacy of cell therapy. The aim of this Study was to elucidate the feasibility of a combination Of ultrasound and microbubbles (US-MB) for delivery of small interfering RNA (siRNA) into mesenchymal stem cells (MSC). Although cell damage was observed after US-MB treatment, the transfection efficiency determined using fluorescent-labeled siRNA was significantly increased after US-MB. Furthermore, the intracellular delivery of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) siRNA by US-MB resulted in significant knockdown of PTEN mRNA expression and activation of Akt, a mediator of a survival signaling pathway. Our results indicate that US-MB could serve as a nonviral delivery method of siRNA into MSC. The transplantation of genetically modified MSC by US-MB Could be a useful strategy for regenerative medicine in the future. (C) 2008 Elsevier B.V. All rights reserved.