Enhanced O2 Delivery to C3A Hepatocytes

增强 C3A 肝细胞的 O2 输送

• 批准号: 7141047
• 负责人: Andre Francis Palmer
• 金额: $ 19.95万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7141047
• 关键词: assistive device /technology; bioreactors; biotransformation; cell differentiation; detoxification; electrodes; erythrocytes; hollow fiber separation technique; liver cells; liver circulation; liver function; mathematics; oxygen consumption; oxygen transport; tissue /cell culture; total artificial organ

DESCRIPTION (provided by applicant): The bioartificial liver assist device (BLAD) utilizes hepatocytes, maintained within an extracorporeal artificial device (commonly a hollow fiber (HF) bioreactor), to reproduce a broad range of liver functions. However, several challenges must still be overcome in the creation of a viable BLAD, including providing appropriate oxygenation to the hepatocytes. Maintaining hepatocyte viability and differentiated function is highly dependent on oxygen provision. 1 promising way to deliver and sustain adequate oxygen levels is through the addition of an oxygen carrier, such as bovine red blood cells (bRBCs), to the media circulating within the device. We hypothesize that the use of bRBCs within a BLAD will allow for increased oxygen delivery, thus promoting prolonged differentiated function and preservation of cell mass. We plan to test this hypothesis by pursuing the following 2 specific aims: 1) Measure and correlate the hepatic HF bioreactor global hepatocyte oxygen consumption (GHOC) with hepatocyte proliferation and metabolic and synthetic functions when bRBCs (either normal or cross-linked) are present in the circulating media at varied bRBC concentrations and at varied inlet partial pressures of oxygen; and 2) Measure and correlate the hepatic HF bioreactor GHOC with hepatocyte biotransformation and detoxification functions under differing oxygenation scenarios. This project is significant in that it is a detailed examination of the impact of oxygen levels on hepatocyte function and viability when cultured within a HF bioreactor; which to the best of our knowledge is not well understood. The success of any or both of these specific aims will aid in achieving the long-term goal of this application, which is to design a BLAD that is capable of sustaining a wide variety of liver functions. The knowledge gained from this study is expected to be of benefit in the design of hepatocyte containing HF bioreactors for use as potential BLADs.

描述（由申请人提供）：生物人工肝辅助装置（BLAD）利用肝细胞，维持在体外人工装置（通常是中空纤维（HF）生物反应器）中，以重现广泛的肝功能。然而，在创造一个可行的BLAD的过程中，仍然需要克服一些挑战，包括为肝细胞提供适当的氧合。维持肝细胞活力和分化功能高度依赖于氧气供应。输送和维持足够氧气水平的一种有希望的方法是通过向设备内循环的介质中添加氧载体，如牛红细胞（brbc）。我们假设在BLAD内使用brbc将允许增加氧气输送，从而促进长时间的分化功能和细胞团的保存。我们计划通过以下两个具体目标来验证这一假设：1)当bRBC（正常或交联）存在于不同bRBC浓度和不同入口氧分压的循环介质中时，测量并关联肝HF生物反应器总体肝细胞耗氧量（GHOC）与肝细胞增殖、代谢和合成功能；2)测量肝HF生物反应器GHOC在不同氧合情况下与肝细胞生物转化和解毒功能的关系。该项目意义重大，因为它详细检查了在HF生物反应器中培养时氧水平对肝细胞功能和活力的影响；据我们所知，这一点还没有得到很好的理解。这些特定目标中的任何一个或两个的成功将有助于实现该应用的长期目标，即设计能够维持多种肝功能的BLAD。从这项研究中获得的知识预计将有助于设计含HF的肝细胞生物反应器，用于潜在的blad。