Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs.
Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs.
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DOI：
10.1016/j.omtn.2018.09.005
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发表时间：
2018-12-07
期刊：
影响因子：
--
通讯作者：
Avci-Adali M
中科院分区：
文献类型：
--
作者：
Steinle H;Golombek S;Behring A;Schlensak C;Wendel HP;Avci-Adali M
内皮祖细胞在心肌梗死、卒中、急性肢体缺血等缺血组织血管重建中的应用具有巨大的临床潜力。然而，内皮祖细胞在缺血组织中的低存留率和植入率以及移植干细胞的低存活率仍然阻碍了其在临床上的成功应用。因此，在这项研究中，我们首次利用合成的α来改造小鼠内皮祖细胞，以瞬时产生促血管生成因子血管内皮生长因子-A(VEGFA)、基质细胞衍生因子-1α(SDF-1)和血管生成素-1(Ang-1)。将合成的α导入细胞后，与未处理的内皮祖细胞相比，血管内皮生长因子-A、血管内皮细胞生长因子-1和血管紧张素-1的蛋白表达显著增加。因此，与未经处理的内皮祖细胞相比，基因工程的内皮祖细胞显示出显著的趋化活性，并显著提高了对内皮祖细胞的吸引力。此外，转导Ang-1mRNA的内皮细胞具有较强的创面愈合能力。12小时后，划痕试验中94%的创面区域闭合，而未经处理的EPC约有45%闭合。此外，血管内皮生长因子-1或α-1α的转染组也能显著提高体外成管能力，但同时转导血管内皮生长因子-A、血管内皮生长因子-1和血管生成素-1mRNA的效果最强。在体内鸡绒毛膜尿囊膜(CAM)实验中，Ang-1mRNA转染组的血管生成能力最强，血管密度和总血管网络长度显著增加。综上所述，这项研究表明，EPC可以成功地与编码促血管生成因子的合成mRNAs一起工程，以提高其在慢性或急性缺血性疾病患者中的治疗血管生成潜力。
The application of endothelial progenitor cells (EPCs) for the revascularization of ischemic tissues, such as after myocardial infarction, stroke, and acute limb ischemia, has a huge clinical potential. However, the low retention and engraftment of EPCs as well as the poor survival of migrated stem cells in ischemic tissues still hamper the successful clinical application. Thus, in this study, we engineered, for the first time, murine EPCs with synthetic mRNAs to transiently produce proangiogenic factors vascular endothelial growth factor-A (VEGF-A), stromal cell-derived factor-1α (SDF-1α), and angiopoietin-1 (ANG-1). After the transfection of cells with synthetic mRNAs, significantly increased VEGF-A, SDF-1α, and ANG-1 protein levels were detected compared to untreated EPCs. Thereby, mRNA-engineered EPCs showed significantly increased chemotactic activity versus untreated EPCs and resulted in significantly improved attraction of EPCs. Furthermore, ANG-1 mRNA-transfected EPCs displayed a strong wound-healing capacity. Already after 12 hr, 94% of the created wound area in the scratch assay was closed compared to approximately 45% by untreated EPCs. Moreover, the transfection of EPCs with ANG-1 or SDF-1α mRNA also significantly improved the in vitro tube formation capacity; however, the strongest effect could be detected with EPCs simultaneously transfected with VEGF-A, SDF-1α, and ANG-1 mRNA. In the in vivo chicken chorioallantoic membrane (CAM) assay, EPCs transfected with ANG-1 mRNA revealed the strongest angiogenetic potential with significantly elevated vessel density and total vessel network length. In conclusion, this study demonstrated that EPCs can be successfully engineered with synthetic mRNAs encoding proangiogenic factors to improve their therapeutic angiogenetic potential in patients experiencing chronic or acute ischemic disease.
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影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
4.3
作者：
BAFFOUR, R;BERMAN, J;FRIEDMANN, P
通讯作者：
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影响因子：
4.3
作者：
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通讯作者：
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DOI：
10.1016/j.biocel.2008.03.012
发表时间：
2008-01-01
影响因子：
4
作者：
Jiang, Meng;Wang, Binyao;Pu, Jun
通讯作者：
Pu, Jun
影响因子：
3.5
作者：
Minami, Yoshiyasu;Nakajima, Toshiaki;Sahara, Makoto
通讯作者：
Sahara, Makoto