Imaging glucose metabolism in perfluorocarbon-perfused hepatocyte bioreactors using positron emission tomography
Imaging glucose metabolism in perfluorocarbon-perfused hepatocyte bioreactors using positron emission tomography
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使用正电子发射断层扫描对全氟化碳灌注的肝细胞生物反应器中的葡萄糖代谢进行成像
DOI：
10.1007/s10047-009-0480-5
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发表时间：
2009
影响因子：
1.3
通讯作者：
S. Merwe
中科院分区：
文献类型：
--
作者：
M. Nieuwoudt;Scholtz Wiggett;S. Malfeld;S. Merwe
体外肝细胞生物反应器的功能尤其取决于维持适当的氧水平和暴露于非实质细胞。一个有吸引力的解决方案，没有免疫后果的病人是纳入全氟化碳氧载体的循环介质和共培养肝细胞与星状细胞。由于生物反应器通常是密封的无菌单元，因此在基质中聚集后，对细胞的有限接触阻碍了代谢功能的证明。一种新的可能性是使用正电子发射断层扫描（PET）图像细胞的放射性葡萄糖摄取在O2限制条件下。在本研究中，对8头猪进行了原代细胞分离程序。在相同的条件下培养细胞接种和无细胞（对照）生物反应器与和无全氟化碳，并使用低氧（5%O2）和环境（20%O2）气体混合物进行充氧。在细胞分离后24小时进行了16次PET扫描，与用原代细胞生物反应器治疗肝衰竭患者的时间尺度相同。在所有情况下，没有全氟化碳的细胞接种生物反应器更具放射性，即，糖酵解作用比全氟化碳更强。这种差异在低氧对生物反应器中是显著的，但在环境对生物反应器中不是。此外，在相同的低氧生物反应器中，循环细胞外稳态葡萄糖水平显着较低，乳酸水平高于环境生物反应器中的那些。在其他研究全氟化碳影响的体外肝细胞研究中也有类似的发现。PET是有吸引力的研究原位O2依赖的生物反应器代谢，因为它的视觉和数字量化的输出。长期代谢研究（例如，5-10研究全氟化碳对生物反应器寿命的影响将在未来补充这些发现。
In vitro hepatocyte bioreactor functionality depends particularly on maintaining appropriate oxygen levels and exposure to nonparenchymal cells. An attractive solution without immunological consequences to the patient is incorporating a perfluorocarbon oxygen carrier in the circulating medium and co-culturing hepatocytes with stellate cells. Since bioreactors are normally sealed sterile units, demonstrating metabolic functionality is hindered by limited access to the cells after their aggregation in the matrix. A novel possibility is to use positron emission tomography (PET) to image cellular radioactive glucose uptake under O2-limited conditions. In this study, primary cell isolation procedures were carried out on eight pigs. Pairs of cell-seeded and cell-free (control) bioreactors with and without perfluorocarbon were cultured under identical conditions and were oxygenated using hypoxic (5% O2) and ambient (20% O2) gas mixes. Sixteen PET scans were conducted 24 h after cell isolation, the same timescale as that involved in treating a liver failure patient with a primary-cell bioreactor. In all cases, cell-seeded bioreactors without perfluorocarbon were more radioactive, i.e., were more glycolytic, than those with perfluorocarbon. This difference was significant in the hypoxic pair of bioreactors but not in the ambient pair of bioreactors. Additionally, in the same hypoxic bioreactors, circulating extracellular steady-state glucose levels were significantly lower and lactate levels were higher than those in the ambient bioreactors. Similar findings have been made in other in vitro hepatocyte studies investigating the effects of perfluorocarbons. PET is attractive for studying in situ O2-dependent bioreactor metabolism because of its visual and numerically quantifiable outputs. Longer-term metabolic studies (e.g., 5–10 days) investigating the effect of perfluorocarbon on bioreactor longevity will complement these findings in the future.
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影响因子：
2.9
作者：
R. Rago;J. Mitchen;G. Wilding
通讯作者：
R. Rago;J. Mitchen;G. Wilding
DOI：
10.1007/10_029
发表时间：
2007-01-01
期刊：
TISSUE ENGINEERING II: BASICS OF TISSUE ENGINEERING AND TISSUE APPLICATIONS
影响因子：
--
作者：
Nahmias, Yaakov;Berthiaume, Francois;Yarmush, Martin L.
通讯作者：
Yarmush, Martin L.
影响因子：
3.8
作者：
Allen, JW;Khetani, SR;Bhatia, SN
通讯作者：
Bhatia, SN
影响因子：
--
作者：
Powers, MJ;Janigian, DM;Griffith, LG
通讯作者：
Griffith, LG
影响因子：
3.8
作者：
Allen, JW;Bhatia, SN
通讯作者：
Bhatia, SN