Enhancement of intercellular interaction between iPSC-derived neural progenitor cells and activated endothelial cells using cell surface modification with functional oligopeptides
Enhancement of intercellular interaction between iPSC-derived neural progenitor cells and activated endothelial cells using cell surface modification with functional oligopeptides
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使用功能性寡肽进行细胞表面修饰，增强 iPSC 衍生的神经祖细胞和活化内皮细胞之间的细胞间相互作用
DOI：
10.1039/d1bm01503f
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发表时间：
2022
影响因子：
6.6
通讯作者：
Teramura Yuji
中科院分区：
文献类型：
--
作者：
Goel Isha;Noiri Makoto;Yamauchi Yuka;Kato Koichi;Chung Ung-il;Teramura Yuji
基于细胞的疗法已被用于治疗中风相关疾病，这些疾病在发病后4.5小时内没有可用的治疗选择。虽然组织纤溶酶原激活剂和机械血栓切除术的管理是有效的治疗，其临床实施是有限的可用时间内。在此，我们的目的是使用诱导多能干细胞衍生的神经祖细胞（NPC）治疗中风，在中风区域具有更高的递送效率，这将提高治疗效果。将E-选择素结合寡肽（Esbp）与具有不同分子量（5和40 kDa）的聚乙二醇-缀合脂质（Esbp-PEG-lipid）缀合用于细胞表面修饰。然后，我们通过研究细胞与中风区域模型表面的结合能力，如重组E-选择素固定表面和TNF-α活化的内皮，优化了NPC的细胞表面修饰。结果，发现用Esbp-PEG-脂质修饰NPC的细胞表面通过Esbp与E-选择素的结合诱导与活化的内皮的特异性细胞间相互作用。此外，较短的PEG间隔基适合于细胞间相互作用。因此，我们的技术显示出在细胞治疗中使用的潜力，在梗死区域中具有增强的细胞积累。
Cell-based therapy has been used to treat stroke related disorders, which have no treatment options available 4.5 hours after onset. Although the administration of tissue plasminogen activator and mechanical thrombectomy are potent treatments, their clinical implementation is limited within the available time. Here, we aimed to use induced pluripotent stem cell-derived neural progenitor cells (NPCs) for stroke treatment with higher delivery efficiency in stroke areas, which will improve the therapeutic effect. E-selectin binding oligopeptide (Esbp) was conjugated with poly(ethylene glycol)-conjugated-lipid (Esbp-PEG-lipid) with different molecular weights of PEG (5 and 40 kDa) for cell surface modification. Then, we optimized the cell surface modification of NPCs by studying cell-binding ability onto the model surfaces of stroke areas, such as recombinant E-selectin-immobilized surfaces and TNF-α activated endothelium. As a result, the cell surface modification of NPCs with Esbp-PEG-lipid was found to induce specific intercellular interactions with the activated endothelium through the binding of Esbp with E-selectin. Additionally, the shorter PEG spacer was suitable for intercellular interactions. Thus, our technique shows potential for use in cell therapy with enhanced cell accumulation in infarct areas.