Sprandel U, Hubbard A R, Chalmers R A
Res Exp Med (Berl). 1980;177(1):13-7. doi: 10.1007/BF01851627.
Resealed erythrocyte 'ghosts' have been proposed as biodegradable in vivo carriers for exogenous enzymes in the therapy of inherited metabolic diseases. Extended animal studies are essential prior to clinical application. The survival of rabbit erythrocyte 'ghosts' has been studied to find a suitable animal model. In vitro experiments have shown that incorporation of macromolecules into rabbit erythrocyte 'ghosts' is much lower than into human erythrocyte 'ghosts'. This could be related to the continuous cell destruction during 'ghost' preparation procedures. Rapid destruction of 'ghosts' in the circulation was obtained in all experiments particularly in the first minutes and hours. Cells surviving this initial period showed a longer life span and kinetics of further cell destruction followed a logarithmic function similar to that of normal erythrocytes. The experimental use of rabbits appears limited to studies where rapid uptake of the enzyme is required and other animal models must be studied when prolonged survival of the erythrocyte 'ghosts' is required, e.g., as the site of substrate degradation in the circulation.
重新封闭的红细胞“空壳”已被提议作为可在体内生物降解的载体，用于遗传性代谢疾病治疗中的外源性酶。在临床应用之前，进行广泛的动物研究至关重要。已对兔红细胞“空壳”的存活情况进行了研究，以寻找合适的动物模型。体外实验表明，大分子掺入兔红细胞“空壳”的量远低于掺入人红细胞“空壳”的量。这可能与“空壳”制备过程中细胞的持续破坏有关。在所有实验中，尤其是在最初的几分钟和几小时内，循环中的“空壳”迅速被破坏。在这一初始阶段存活下来的细胞显示出更长的寿命，进一步细胞破坏的动力学遵循类似于正常红细胞的对数函数。兔子的实验用途似乎仅限于需要快速摄取酶的研究，而当需要红细胞“空壳”长时间存活时，例如作为循环中底物降解的部位，则必须研究其他动物模型。
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