PNAS：纳米颗粒强化干细胞刺激血管生长（附原文）

细胞海洋

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科学家培育出了用纳米颗粒强化的干细胞，它可能刺激新血管的生长并恢复受伤动物的肢体功能。尽管干细胞疗法在替换受损组织并治疗诸如心脏病发作和中风等疾病方面拥有很大的潜力，这些疗法的应用经常被证明不能有效地再生组织和生长新的血管。一个关键的问题在于经过改造的细胞不能产生足够数量的刺激血管生长的关键蛋白——诸如血管内皮生长因子（VEGF）。增加这些生长因子在干细胞中的产量的方法——通过使用病毒载体或化学试剂——常常导致危险的副作用或效率低下。. `: k4 V, X  D* M: J( _+ _8 \
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Daniel Anderson及其同事通过利用非毒性、生物可降解的纳米颗粒提供生长因子DNA，从而改善了VEGF在间叶干细胞和人类胚胎干细胞中的产量。对于肢体受损的小鼠，与未经修改或者用传统试剂修改的干细胞相比，这些强化的干细胞在移植后的两周时间把血管密度提高到了至多4倍。这组作者说，在4周时间里，这些动物与对照组相比，充分增强了血管生长和肢体功能，肌肉退化也减少了。
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3楼原文 感谢胞友apengforever 提供

细胞海洋

原始出处：0 |  D0 e! a" c: R) x+ S

0 D, H, u8 y+ WPNAS October 5, 2009, doi: 10.1073/pnas.0905432106
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Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles, [! k9 C; i' k! L0 l; m

* }9 x6 c2 u. e4 E5 kFan Yanga,1, Seung-Woo Choa,b,1, Sun Mi Sona, Said R. Bogatyreva,c, Deepika Singha, Jordan J. Greena, Ying Meia, Sohyun Parkd, Suk Ho Bhange, Byung-Soo Kime, Robert Langera,f and Daniel G. Andersonf,2
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Departments of aChemical Engineering and
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7 `9 y* [0 v7 [fDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; ; J+ F! o8 q) G9 W8 n
bDepartment of Anesthesiology, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115; 6 m0 v# U4 `) T
cV. I. Shumakov Research Institute of Transplantation and Artificial Organs, Moscow 123182, Russia; and
* J& _$ M+ d' d/ O7 {5 EeSchool of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea
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1 e2 ^1 a4 T. n1 b$ KStem cells hold great potential as cell-based therapies to promote vascularization and tissue regeneration. However, the use of stem cells alone to promote angiogenesis remains limited because of insufficient expression of angiogenic factors and low cell viability after transplantation. Here, we have developed vascular endothelial growth factor (VEGF) high-expressing, transiently modified stem cells for the purposes of promoting angiogenesis. Nonviral, biodegradable polymeric nanoparticles were developed to deliver hVEGF gene to human mesenchymal stem cells (hMSCs) and human embryonic stem cell-derived cells (hESdCs). Treated stem cells demonstrated markedly enhanced hVEGF production, cell viability, and engraftment into target tissues. S.c. implantation of scaffolds seeded with VEGF-expressing stem cells (hMSCs and hESdCs) led to 2- to 4-fold-higher vessel densities 2 weeks after implantation, compared with control cells or cells transfected with VEGF by using Lipofectamine 2000, a leading commercial reagent. Four weeks after intramuscular injection into mouse ischemic hindlimbs, genetically modified hMSCs substantially enhanced angiogenesis and limb salvage while reducing muscle degeneration and tissue fibrosis. These results indicate that stem cells engineered with biodegradable polymer nanoparticles may be therapeutic tools for vascularizing tissue constructs and treating ischemic disease.

apengforever

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guojingjing

干细胞移植发挥修复作用的一个机制就是促进血管形成，而新生血管又能促进干细胞的迁移分化。但是我一直有一个疑问，这种angiogenesis的上调是否有副作用？损伤的血管（例如脑中风时梗死的血管）的命运是怎么样的？