Gundersen Sharon I, Palmer Andre F
Department of Biomolecular and Chemical Engineering, University of Notre Dame, 182 Fitzpatrick Hall, Notre Dame, Indiana 46656, USA.
Biotechnol Bioeng. 2007 Apr 15;96(6):1199-210. doi: 10.1002/bit.21204.
Methoxypolyethylene glycol (mPEG) covalently bound to the surface of human red blood cells (hRBCs) has been shown to decrease immunological recognition of hRBC surface antigens (Bradley et al., 2002). However, there is an increasing shortage of hRBC donations, thus making hRBCs scarce and expensive (Davey, 2004; Riess, 2001). The goal of this study is to similarly PEGylate the surface of bovine RBCs (bRBCs) with the aim of reducing the demand on human blood donations needed for blood transfusions. This study investigates the feasibility of modifying the surface of bRBCs with the succinimidyl ester of methoxypolyethylene glycol propionic acid (SPA-mPEG) for use as a potential blood substitute. The oxygen binding affinity of PEGylated bRBCs was moderately increased with increasing initial SPA-mPEG concentrations up to 4 mM when reacted with bRBCs at a hematocrit of 12%. Oxygen transport simulations verified that SPA-mPEG conjugated bRBCs could still transport oxygen to pancreatic islet tissues even under extreme conditions. PEGylated bRBCs reconstituted to a hematocrit of 40% exhibited viscosities on the order of approximately 3 cp, similar to hRBCs at the same hematocrit. Taken together, the results of this study demonstrate the success of PEGylating bRBCs to yield modified cells with oxygen binding, transport and flow properties similar to that of hRBCs.
已证明共价结合到人红细胞(hRBCs)表面的甲氧基聚乙二醇(mPEG)可降低对hRBC表面抗原的免疫识别(Bradley等人,2002年)。然而,hRBC捐献日益短缺,从而使hRBC变得稀缺且昂贵(Davey,2004年;Riess,2001年)。本研究的目的是类似地用聚乙二醇修饰牛红细胞(bRBCs)表面,以减少输血所需的人类血液捐献需求。本研究调查了用甲氧基聚乙二醇丙酸琥珀酰亚胺酯(SPA-mPEG)修饰bRBCs表面作为潜在血液替代品的可行性。当在血细胞比容为12%的情况下与bRBCs反应时,随着初始SPA-mPEG浓度增加至4 mM,聚乙二醇化bRBCs的氧结合亲和力适度增加。氧运输模拟证实,即使在极端条件下,SPA-mPEG共轭bRBCs仍能将氧气输送到胰岛组织。重构至血细胞比容为40%的聚乙二醇化bRBCs的粘度约为3 cp,与相同血细胞比容的hRBCs相似。综上所述,本研究结果证明了聚乙二醇化bRBCs成功产生了具有与hRBCs相似的氧结合、运输和流动特性的修饰细胞。