Sakai Hiromi, Sou Keitaro, Horinouchi Hirohisa, Kobayashi Koichi, Tsuchida Eishun
Research Institute for Science and Engineering, Waseda University, Tokyo, Japan.
Artif Organs. 2009 Feb;33(2):139-45. doi: 10.1111/j.1525-1594.2008.00698.x.
Blood transfusion systems have greatly benefited human health and welfare. Nevertheless, some problems remain: infection, blood type mismatching, immunological response, short shelf life, and screening test costs. Blood substitutes have been under development for decades to overcome such problems. Plasma component substitutes have already been established: plasma expanders, electrolytes, and recombinant coagulant factors. Herein, we focus on the development of red blood cell (RBC) substitutes. Side effects hindered early development of cell-free hemoglobin (Hb)-based oxygen carriers (HBOCs) and underscored the physiological importance of the cellular structure of RBCs. Well-designed artificial oxygen carriers that meet requisite criteria are expected to be realized eventually. Encapsulation of Hb is one idea to shield the toxicities of molecular Hbs. However, intrinsic issues of encapsulated Hbs must be resolved: difficulties related to regulating the molecular assembly, and management of its physicochemical and biochemical properties. Hb-vesicles (HbV) are a cellular type of HBOC that overcome these issues. The in vivo safety and efficacy of HbV have been studied extensively. The results illustrate the potential of HbV as a transfusion alternative and promise its use for other clinical applications that remain unattainable using RBC transfusion.
输血系统极大地促进了人类健康和福祉。然而,仍存在一些问题:感染、血型不匹配、免疫反应、保质期短以及筛查测试成本。几十年来一直在研发血液替代品以克服这些问题。血浆成分替代品已经确立:血浆扩容剂、电解质和重组凝血因子。在此,我们重点关注红细胞(RBC)替代品的研发。副作用阻碍了基于无细胞血红蛋白(Hb)的氧载体(HBOCs)的早期发展,并凸显了红细胞细胞结构的生理重要性。最终有望实现符合必要标准的精心设计的人工氧载体。封装血红蛋白是一种屏蔽分子血红蛋白毒性的思路。然而,必须解决封装血红蛋白的内在问题:与调节分子组装相关的困难,以及其物理化学和生化性质的管理。血红蛋白囊泡(HbV)是一种克服这些问题的细胞型HBOC。已经广泛研究了HbV在体内的安全性和有效性。结果表明HbV作为输血替代品的潜力,并有望将其用于使用红细胞输血仍无法实现的其他临床应用。