Progress in hepatocyte status detection and its application in bioartificial liver support system_Journal of Biomedical Engineering

Authors：

XU Shichen ^1,2 , WU Changzhe ¹ , ZHANG Guanghao ¹ , ZHANG Cheng ¹ ,  HUO Xiaolin ^1,2

1. Beijing Key Laboratory of Biological Electromagnetics, Institute of Electrical Engineering of the Chinese Academy of Sciences, Beijing 100190, P.R.China;
2. University of Chinese Academy of Sciences, Beijing 100049, P.R.China;

Corresponding author：

Keywords：

bioartificial liver support system; bioreactor; hepatocyte status; indicator; detection method

DOI：

10.7507/1001-5515.201705066

Video：

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Bioartificial liver support system (BALSS) provides a new way to treat liver failure and leaves more time for patients who are waiting for liver transplantation. It has detoxification function as well as the human liver, at the same time it can provide nutrition and improve the internal environment inside human body. Bioreactors and hepatocytes with good biological activity are the cores of BALSS which determine the treatment effect. However, in the course of prolonged treatment, the function and activity of hepatocytes might be greatly changed which could influence the efficacy. Therefore, it is very important to detect the status of the hepatocytes in BALSS. This paper presents some common indicators of cell activity, detoxification and synthetic functions, and also introduces the commonly detection methods corresponding to each indicator. Finally, we summarize the application of detection methods of the hepatocyte status in BALSS and discuss its development trend.

Citation： XU Shichen, WU Changzhe, ZHANG Guanghao, ZHANG Cheng, HUO Xiaolin. Progress in hepatocyte status detection and its application in bioartificial liver support system. Journal of Biomedical Engineering, 2018, 35(1): 151-155. doi: 10.7507/1001-5515.201705066 Copy

1.	王英杰. 生物人工肝. 北京: 人民卫生出版社, 2002.
2.	Han Bing, Shi Xiaolei, Zhang Yue, et al. Microbiological safety of a novel bio-artificial liver support system based on porcine hepatocytes: a experimental study. Eur J Med Res, 2012, 17: 13.
3.	Bañares R, Catalina M V, Vaquero J. Molecular adsorbent recirculating system and bioartificial devices for liver failure. Clin Liver Dis, 2014, 18(4): 945-956.
4.	Nicolas C T, Hickey R D, Chen H S, et al. Concise review: liver regenerative medicine: from hepatocyte transplantation to bioartificial livers and bioengineered grafts. Stem Cells, 2017, 35(1): 42-50.
5.	陈煜, 李爽. 人工肝支持系统的临床应用. 临床荟萃, 2016, 31(7): 717-722.
6.	鲁艳玲, 张晓娟, 马建奇, 等. 血浆置换联合血液灌流治疗肝衰竭的疗效观察. 疑难病杂志, 2015, 14(3): 254-257.
7.	van Wenum M, Chamuleau R AFM, van Gulik T M, et al. Bioartificial livers in vitro and in vivo: tailoring biocomponents to the expanding variety of applications. Expert Opin Biol Ther, 2014, 14(12): 1745-1760.
8.	Yu Chengbo, Pan Xiaoping, Yu Liang, et al. Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers. World Journal of Gastroenterology, 2014, 20(22): 6869-6877.
9.	Poyck P P C, Hoekstra R, Chhatta A, et al. Time-related analysis of metabolic liver functions, cellular morphology, and gene expression of hepatocytes cultured in the bioartificial liver of the Academic Medical Center in Amsterdam (AMC-BAL). Tissue Eng, 2007, 13(6): 1235-1246.
10.	Sussman N L, Kelly J H. Artificial liver. Clin Gastroenterol Hepatol, 2014, 12: 1439-1442.
11.	Zhang Zhi, Zhao Yichao, Cheng Yuan, et al. Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure. World J Gastroenterol, 2014, 20(46): 17399-17406.
12.	Shi Xiaolei, Gao Yimeng, Yan Yupeng, et al. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes. Cell Res, 2016, 26(2): 206-216.
13.	Liu Yuhan, Lu Keding, Dong Huabin, et al. In situ monitoring of atmospheric nitrous acid based on multi-pumping flow system and liquid waveguide capillary cell. J Environ Sci (China), 2016, 43: 273-284.
14.	高景波, 王雪妹, 韦旭, 等. 血站实验室 ALT 检测性能验证方法的探讨. 中国输血杂志, 2015, 28(9): 1094-1097.
15.	汪辛如. 干化学法与速率法在不同血液样本 ALT 检测中的应用. 临床输血与检验, 2014, 16(1): 61-63.
16.	黄腊梅. 巴中市无偿献血者丙氨酸氨基转移酶检测结果研究. 检验医学与临床, 2016, 13(4): 524-525.
17.	马静瑶. 干化学法和速率法在献血前 ALT 筛查中的应用比较. 临床医学研究与实践, 2017, 2(6): 164-165.
18.	李建元. 游泳池水中尿素的两种测定方法比较. 中国卫生检验杂志, 2011, 21(3): 763-764.
19.	李俊华. 酶法尿素检测试剂的改进及性能评价. 检验医学, 2014, 29(4): 390-393.
20.	周小微, 李安全. 血清抗体与快速尿素酶检测幽门螺杆菌感染的灵敏度及特异性分析. 现代医药卫生, 2016, 32(22): 3502-3503.
21.	黄报亮, 吴清平, 邓金花, 等. 尿素检测方法的研究进展及其快速检测产品现状. 光谱实验室, 2013, 30(5): 2565-2571.
22.	Hassnein W A, Uluer M C, Woodall J D, et al. Bio-Artificial liver generation using multilineage xenogenic and heterogenic cells. J Am Coll Surg, 2016, 223(4, Suppl 2): e50.
23.	唐海涛. 白蛋白稀释液联合 706 代血浆在人工肝治疗乙型肝功能衰竭中的疗效观察. 临床医药文献电子杂志, 2016, 3(25): 5086-5087.
24.	柯柳华, 孙一帆, 潘红梅. 血清前白蛋白和白蛋白在 196 例肝病患者中的检测分析. 中国民族民间医药, 2014(23): 92-94.
25.	姜春华. 人工肝支持系统在肝功能衰竭中的应用进展. 临床合理用药杂志, 2017, 10(3C): 171-172.
26.	Struecker B, Raschzok N, Sauer I M. Liver support strategies: cutting-edge technologies. Nat Rev Gastroenterol Hepatol, 2014, 11(3): 166-176.
27.	Nibourg G A, Hoekstra R, van der Hoeven T V, et al. Increased hepatic functionality of the human hepatoma cell line HepaRG cultured in the AMC bioreactor. International Journal of Biochemistry & Cell Biology, 2013, 45(8): 1860-1868.
28.	高义萌, 孙露露, 惠利健. 生物人工肝研究进展. 生命科学, 2016, 28(8): 915-920.
29.	郭欢, 邵安良, 程祥, 等. 生物人工肝用海藻酸钠/壳聚糖微囊的安全性和生物功能评价. 药物分析杂志, 2016, 36(1): 36-45.
30.	Damania A, Kumar A, Sarin S K, et al. Optimized performance of the integrated hepatic cell-loaded cryogel-based bioreactor with intermittent perfusion of acute liver failure plasma. J Biomed Mater Res B Appl Biomater, 2017, 1: 1-11.
31.	Wang Gang, Feng Enmin, Xiu Zhilong. Modeling and parameter identification of microbial bioconversion in fed-batch cultures. J Process Control, 2008, 18(5): 458-464.
32.	Hollmann M, Boertz J, Dopp E, et al. Parallel on-line detection of a methylbismuth species by hyphenated GC/EI-MS/ICP-MS technique as evidence for bismuth methylation by human hepatic cells. Metallomics, 2010, 2(1): 52-56.
33.	郭庆强, 林建强, 李歧强. 微生物发酵过程的细胞密度在线检测与底物浓度实时控制. 中国科学技术大学学报, 2012, 42(7): 584-589.
34.	Murray N P, Fuentealba C, Reyes E, et al. A comparison of 3 on-line nomograms with the detection of primary circulating prostate cells to predict prostate cancer at initial biopsy. Actas Urol Esp, 2017, 41(4): 234.
35.	项红升, 刘剑峰, 李明, 等. 生物型人工肝的在线快速细胞监测系统. 生物医学工程与临床, 2005, 9(1): 45-48.
36.	Tan S J, Lakshmi R L, Chen Pengfei, et al. Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. Biosens Bioelectron, 2010, 26(4, SI): 1701-1705.
37.	Sequist L V, Nagrath S, Toner M, et al. The CTC-chip: an exciting new tool to detect circulating tumor cells in lung cancer patients. J Thorac Oncol, 2009, 4(3): 281-283.
38.	修小青, 霍小林, 李明, 等. 生物人工肝细胞状态在线微检测系统的研究. 现代科学仪器, 2009, 8(4): 11-14.
39.	Cao Y, Wu C Z, Huo X L, et al. Design and simulation of a novel micro-mixer for detecting cell status in bio-artificial liver. Appl Mech Mater, 2012, 246-247: 241-245.
40.	Wu Changzhe, Cao Yue, Huo Xiaolin, et al. Simulation and experimental research on micro-channel for detecting cell status in bio-artificial liver. Technol Health Care, 2015, 23(Suppl 2): S365-S371.
41.	方云, 汤治元, 张倩, 等. 人肝癌细胞电阻抗特性的实验研究. 生物医学工程学杂志, 2014, 31(5): 1070-1074.
42.	Emma P, Kamen A. Real-time monitoring of influenza virus production kinetics in HEK293 cell cultures. Biotechnol Prog, 2013, 29(1): 275-284.

1. 王英杰. 生物人工肝. 北京: 人民卫生出版社, 2002.
2. Han Bing, Shi Xiaolei, Zhang Yue, et al. Microbiological safety of a novel bio-artificial liver support system based on porcine hepatocytes: a experimental study. Eur J Med Res, 2012, 17: 13.
3. Bañares R, Catalina M V, Vaquero J. Molecular adsorbent recirculating system and bioartificial devices for liver failure. Clin Liver Dis, 2014, 18(4): 945-956.
4. Nicolas C T, Hickey R D, Chen H S, et al. Concise review: liver regenerative medicine: from hepatocyte transplantation to bioartificial livers and bioengineered grafts. Stem Cells, 2017, 35(1): 42-50.
5. 陈煜, 李爽. 人工肝支持系统的临床应用. 临床荟萃, 2016, 31(7): 717-722.
6. 鲁艳玲, 张晓娟, 马建奇, 等. 血浆置换联合血液灌流治疗肝衰竭的疗效观察. 疑难病杂志, 2015, 14(3): 254-257.
7. van Wenum M, Chamuleau R AFM, van Gulik T M, et al. Bioartificial livers in vitro and in vivo: tailoring biocomponents to the expanding variety of applications. Expert Opin Biol Ther, 2014, 14(12): 1745-1760.
8. Yu Chengbo, Pan Xiaoping, Yu Liang, et al. Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers. World Journal of Gastroenterology, 2014, 20(22): 6869-6877.
9. Poyck P P C, Hoekstra R, Chhatta A, et al. Time-related analysis of metabolic liver functions, cellular morphology, and gene expression of hepatocytes cultured in the bioartificial liver of the Academic Medical Center in Amsterdam (AMC-BAL). Tissue Eng, 2007, 13(6): 1235-1246.
10. Sussman N L, Kelly J H. Artificial liver. Clin Gastroenterol Hepatol, 2014, 12: 1439-1442.
11. Zhang Zhi, Zhao Yichao, Cheng Yuan, et al. Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure. World J Gastroenterol, 2014, 20(46): 17399-17406.
12. Shi Xiaolei, Gao Yimeng, Yan Yupeng, et al. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes. Cell Res, 2016, 26(2): 206-216.
13. Liu Yuhan, Lu Keding, Dong Huabin, et al. In situ monitoring of atmospheric nitrous acid based on multi-pumping flow system and liquid waveguide capillary cell. J Environ Sci (China), 2016, 43: 273-284.
14. 高景波, 王雪妹, 韦旭, 等. 血站实验室 ALT 检测性能验证方法的探讨. 中国输血杂志, 2015, 28(9): 1094-1097.
15. 汪辛如. 干化学法与速率法在不同血液样本 ALT 检测中的应用. 临床输血与检验, 2014, 16(1): 61-63.
16. 黄腊梅. 巴中市无偿献血者丙氨酸氨基转移酶检测结果研究. 检验医学与临床, 2016, 13(4): 524-525.
17. 马静瑶. 干化学法和速率法在献血前 ALT 筛查中的应用比较. 临床医学研究与实践, 2017, 2(6): 164-165.
18. 李建元. 游泳池水中尿素的两种测定方法比较. 中国卫生检验杂志, 2011, 21(3): 763-764.
19. 李俊华. 酶法尿素检测试剂的改进及性能评价. 检验医学, 2014, 29(4): 390-393.
20. 周小微, 李安全. 血清抗体与快速尿素酶检测幽门螺杆菌感染的灵敏度及特异性分析. 现代医药卫生, 2016, 32(22): 3502-3503.
21. 黄报亮, 吴清平, 邓金花, 等. 尿素检测方法的研究进展及其快速检测产品现状. 光谱实验室, 2013, 30(5): 2565-2571.
22. Hassnein W A, Uluer M C, Woodall J D, et al. Bio-Artificial liver generation using multilineage xenogenic and heterogenic cells. J Am Coll Surg, 2016, 223(4, Suppl 2): e50.
23. 唐海涛. 白蛋白稀释液联合 706 代血浆在人工肝治疗乙型肝功能衰竭中的疗效观察. 临床医药文献电子杂志, 2016, 3(25): 5086-5087.
24. 柯柳华, 孙一帆, 潘红梅. 血清前白蛋白和白蛋白在 196 例肝病患者中的检测分析. 中国民族民间医药, 2014(23): 92-94.
25. 姜春华. 人工肝支持系统在肝功能衰竭中的应用进展. 临床合理用药杂志, 2017, 10(3C): 171-172.
26. Struecker B, Raschzok N, Sauer I M. Liver support strategies: cutting-edge technologies. Nat Rev Gastroenterol Hepatol, 2014, 11(3): 166-176.
27. Nibourg G A, Hoekstra R, van der Hoeven T V, et al. Increased hepatic functionality of the human hepatoma cell line HepaRG cultured in the AMC bioreactor. International Journal of Biochemistry & Cell Biology, 2013, 45(8): 1860-1868.
28. 高义萌, 孙露露, 惠利健. 生物人工肝研究进展. 生命科学, 2016, 28(8): 915-920.
29. 郭欢, 邵安良, 程祥, 等. 生物人工肝用海藻酸钠/壳聚糖微囊的安全性和生物功能评价. 药物分析杂志, 2016, 36(1): 36-45.
30. Damania A, Kumar A, Sarin S K, et al. Optimized performance of the integrated hepatic cell-loaded cryogel-based bioreactor with intermittent perfusion of acute liver failure plasma. J Biomed Mater Res B Appl Biomater, 2017, 1: 1-11.
31. Wang Gang, Feng Enmin, Xiu Zhilong. Modeling and parameter identification of microbial bioconversion in fed-batch cultures. J Process Control, 2008, 18(5): 458-464.
32. Hollmann M, Boertz J, Dopp E, et al. Parallel on-line detection of a methylbismuth species by hyphenated GC/EI-MS/ICP-MS technique as evidence for bismuth methylation by human hepatic cells. Metallomics, 2010, 2(1): 52-56.
33. 郭庆强, 林建强, 李歧强. 微生物发酵过程的细胞密度在线检测与底物浓度实时控制. 中国科学技术大学学报, 2012, 42(7): 584-589.
34. Murray N P, Fuentealba C, Reyes E, et al. A comparison of 3 on-line nomograms with the detection of primary circulating prostate cells to predict prostate cancer at initial biopsy. Actas Urol Esp, 2017, 41(4): 234.
35. 项红升, 刘剑峰, 李明, 等. 生物型人工肝的在线快速细胞监测系统. 生物医学工程与临床, 2005, 9(1): 45-48.
36. Tan S J, Lakshmi R L, Chen Pengfei, et al. Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. Biosens Bioelectron, 2010, 26(4, SI): 1701-1705.
37. Sequist L V, Nagrath S, Toner M, et al. The CTC-chip: an exciting new tool to detect circulating tumor cells in lung cancer patients. J Thorac Oncol, 2009, 4(3): 281-283.
38. 修小青, 霍小林, 李明, 等. 生物人工肝细胞状态在线微检测系统的研究. 现代科学仪器, 2009, 8(4): 11-14.
39. Cao Y, Wu C Z, Huo X L, et al. Design and simulation of a novel micro-mixer for detecting cell status in bio-artificial liver. Appl Mech Mater, 2012, 246-247: 241-245.
40. Wu Changzhe, Cao Yue, Huo Xiaolin, et al. Simulation and experimental research on micro-channel for detecting cell status in bio-artificial liver. Technol Health Care, 2015, 23(Suppl 2): S365-S371.
41. 方云, 汤治元, 张倩, 等. 人肝癌细胞电阻抗特性的实验研究. 生物医学工程学杂志, 2014, 31(5): 1070-1074.
42. Emma P, Kamen A. Real-time monitoring of influenza virus production kinetics in HEK293 cell cultures. Biotechnol Prog, 2013, 29(1): 275-284.

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