BIOREACTOR WITH DIRECT PLASMA CONTACT FOR LIVER ASSIST

本文介绍了一种新型的玻璃微珠基质生物反应器， 孟山都和华盛顿大学，其中猪肝细胞 聚集到珠子的空隙中，留下通道， 血浆直接通过细胞（如在天然肝脏中）。 与将细胞置于膜另一侧的生物反应器相比 从血浆中，GBM具有：更高的负载能力，更正常的 聚集体内的细胞间连接，更好的传质 化学物质进出血浆，化学功能持续数周， 小时以上（白蛋白溶液灌注期间）。 在第一阶段，我们将 确定GBM是否在异种过程中长期发挥作用， 血浆灌注以及是否存在细胞毒性抗体的损伤。 这些研究将确定GBM是否可以与简单的 血浆灌注回路或是否必须 用来免疫隔离胶质母细胞瘤然后用血清过滤液灌注 含有白蛋白但不含抗体 GBM最终将用于 结合生物逻辑解毒系统， 肝衰竭患者血浆中的肝衰竭毒素 伴随着GBM的化学和合成功能。 建议的商业应用 全世界有超过20亿人感染肝炎病毒， 这些患者中有10%患有慢性肝功能不全。 当 胃肠道出血或感染等并发症导致急性肝硬化 衰竭和昏迷，一种有效且相对便宜的肝脏支持 设备是必要的，以支持病人，直到并发症可以 然后，患者可以恢复正常健康。 的 这种装置的市场比治疗肾脏的装置大得多 失败

A novel bioreactor with glass bead matrix (GBM) has been developed at Monsanto and Washington University, in which porcine hepatocytes aggregate into the interstices of the beads, leaving pathways for passage of plasma directly over the cells (as in the native liver). Versus bioreactors with cells placed on the opposite side of membranes from plasma, the GBM has: higher loading capacity, more normal intercellular connections within the aggregates, better mass transfer of chemicals to and from plasma, and chemical function for weeks rather than hours (during albumin solution perfusion). In Phase I, we will determine whether the GBM functions for long periods during xenogenic plasma perfusion and whether there is damage from cytotoxic antibodies. These studies will determine whether the GBM can be used with a simple plasma perfusion circuit or whether a more complex system must be created to immune-isolate the GBM and perfuse it with a serum filtrate containing albumin but no antibodies. The GBM will eventually be used in conjunction with the BioLogic detoxifier system which will remove hepatic failure toxins from the plasma of patients with hepatic failure concomitant with chemical and synthetic function of the GBM. PROPOSED COMMERCIAL APPLICATION Worldwide, over 2 billion people are infected with hepatitis viruses and 10 percent of these patients have chronic liver insufficiency. When complications such as GI bleeding or infection result in acute hepatic failure and coma, an effective and relatively inexpensive liver support device is needed, to support the patients until the complications can be corrected; the patient can then return to their usual health. The market for such a device is much larger than for devices treating kidney failure.