BIOREACTOR WITH DIRECT PLASMA CONTACT FOR LIVER ASSIST

用于肝脏辅助的直接等离子体接触生物反应器

• 批准号: 2539002
• 负责人: STEPHEN R ASH
• 金额: $ 9.99万
• 依托单位: HEMOCLEANSE, INC
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2539002
• 关键词: animal tissue; antigen antibody reaction; biomedical equipment development; bioreactors; blood treatment; clinical biomedical equipment; extracorporeal circulation; glass; immature animal; laboratory rat; liver cells; mature animal; perfusion; plasma; swine

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.

在 孟山都和华盛顿大学，其中猪肝细胞 汇总到珠子的间隙，留下 血浆直接通过细胞（如天然肝脏）传递。 与生物反应器相比，将细胞放在膜的另一侧 从血浆中，GBM具有：更高的加载能力，更正常 聚集体内的细胞间连接，更好的传质 化学物质与血浆的化学物质和化学功能数周而不是化学功能 比小时（在白蛋白溶液灌注期间）。 在第一阶段，我们将 确定GBM是否在异种期间长期发挥作用 血浆灌注以及是否受到细胞毒性抗体的损害。 这些研究将确定是否可以简单地使用GBM 等离子体灌注电路或更复杂的系统是否必须是 创建以免疫隔离GBM并用血清滤液进行灌注 含有白蛋白，但没有抗体。 GBM最终将使用 与生物学排毒系统结合使用，该系统将去除 肝衰竭患者血浆中的肝衰竭毒素 与GBM的化学和合成功能同时。 拟议的商业应用 全球，超过20亿人感染了肝炎病毒和 这些患者中有10％患有慢性肝功能不全。 什么时候 诸如GI出血或感染之类的并发症导致急性肝 失败和昏迷，有效且相对便宜的肝脏支持 需要设备，以支持患者，直到并发症可以 被纠正；然后，患者可以恢复其通常的健康状况。 这 这种设备的市场比处理肾脏的设备要大得多 失败。