Antigens Protected Functional Red Blood Cells By The Membrane Grafting Of Compact Hyperbranched Polyglycerols
Antigens Protected Functional Red Blood Cells By The Membrane Grafting Of Compact Hyperbranched Polyglycerols
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DOI：
10.3791/50075
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发表时间：
2013-01-01
影响因子：
1.2
通讯作者：
Kizhakkedathu, Jayachandran
中科院分区：
文献类型：
--
作者：
Chapanian, Rafi;Constantinescu, Iren;Kizhakkedathu, Jayachandran
红细胞（RBC）输血对于治疗许多急性和慢性医学问题，如地中海贫血和镰状细胞性贫血至关重要（1-3）。由于红细胞表面存在多种抗原（类似于308种已知抗原(4)），慢性输血治疗患者由于输血红细胞上的次要抗原不匹配而产生同种异体抗体（4,5）。亲水聚合物如聚乙二醇（PEG）和超支化聚甘油（HPG）的接枝在红细胞膜上形成排斥层，阻止抗体与表面抗原的相互作用，而不影响小分子如氧、葡萄糖和离子的通过(3)。目前还没有一种方法可以产生通用的红细胞，部分原因是红细胞表面存在大量抗原（蛋白质和碳水化合物为基础）带来了艰巨的挑战，而这种方法的发展将显著提高输血安全性，并显著提高红细胞的可用性和使用。本文介绍了HPG膜接枝制备抗原保护功能红细胞的实验及其特性。HPGs是高度生物相容性的致密聚合物（6,7），预计将位于围绕脂质膜的细胞糖萼内（8,9）并掩盖RBC表面抗原（10,11）。
Red blood cell (RBC) transfusion is vital for the treatment of a number of acute and chronic medical problems such as thalassemia major and sickle cell anemia (1-3). Due to the presence of multitude of antigens on the RBC surface (similar to 308 known antigens (4)), patients in the chronic blood transfusion therapy develop alloantibodies due to the miss match of minor antigens on transfused RBCs (4, 5). Grafting of hydrophilic polymers such as polyethylene glycol (PEG) and hyperbranched polyglycerol (HPG) forms an exclusion layer on RBC membrane that prevents the interaction of antibodies with surface antigens without affecting the passage of small molecules such as oxygen, glucose, and ions(3). At present no method is available for the generation of universal red blood donor cells in part because of the daunting challenge presented by the presence of large number of antigens (protein and carbohydrate based) on the RBC surface and the development of such methods will significantly improve transfusion safety, and dramatically improve the availability and use of RBCs. In this report, the experiments that are used to develop antigen protected functional RBCs by the membrane grafting of HPG and their characterization are presented. HPGs are highly biocompatible compact polymers (6, 7), and are expected to be located within the cell glycocalyx that surrounds the lipid membrane (8, 9) and mask RBC surface antigens(10, 11).