Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium
Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium
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用寡肽-PEG-脂质修饰人 MSC 表面以选择性结合活化的内皮细胞
DOI：
10.1002/jbm.a.36697
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
and Yuji Teramura
中科院分区：
文献类型：
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作者：
Makoto Noiri;Kenta Asawa;Naoya Okada1;Tomonobu Kodama;Yuichi Murayama;Yuuki Inoue;Kazuhiko Ishihara;Kristina N Ekdahl;Bo Nilsson;and Yuji Teramura
提出了使用间充质干细胞（MSC）用于中风患者的有前途的细胞疗法。因此，我们的目的是使用携带寡肽的聚乙二醇（PEG）-缀合磷脂（PEG-脂质）有效地将人MSC（hMSC）聚集到受损的脑区域，以提高治疗效果，所述寡肽对缺氧样中风下激活的内皮细胞上上调的E-选择素具有特异性。在这里，我们合成了E-选择素结合寡肽（ES-bp），其与具有1至40 kDa的不同分子量的PEG间隔基缀合。我们发现ES-bp可以通过PEG-脂质固定在hMSC表面，而不影响细胞生长和分化为脂肪细胞和骨细胞。还可以控制ES-bp在hMSC表面上的固定（<108 ES-bp/细胞）。当使用具有PEG 5和40 kDa的PEG-脂质时，固定化的ES-bp可以连续固定在细胞膜外部。此外，修饰的hMSC可以特异性地附着到E-选择素固定化表面上，作为人血液中活化内皮的模型表面，表明hMSC上固定有足够数量的ES-bp。因此，该技术是hMSC积聚到脑梗死区域的候选者之一。© 2019 Wiley Periodicals，Inc. J Biomed Mater Res Part A：107A：1779-1792，2019.
Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)‐conjugated phospholipid (PEG‐lipid) carrying an oligopeptide as a ligand, specific for E‐selectin which is upregulated on activated endothelial cells under hypoxia‐like stroke. Here we synthesized E‐selectin‐binding oligopeptide (ES‐bp) conjugated with PEG spacer having different molecular weights from 1 to 40 kDa. We found that ES‐bp can be immobilized onto the hMSC surface through PEG‐lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. It is also possible to control the immobilization of ES‐bp on hMSC surface (<108ES‐bp per cell). Immobilized ES‐bp can be continuously immobilized at the outside of cell membrane when PEG‐lipids with PEG 5 and 40 kDa were used. In addition, the modified hMSC can specifically attach onto E‐selectin‐immobilized surface as a model surface of activated endothelium in human blood, indicating the sufficient number of immobilized ES‐bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1779–1792, 2019.