Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment

K. Nakazawa, H. Ijima, J. Fukuda, R. Sakiyama, Y. Yamashita, M. Shimada, K. Shirabe, E. Tsujita, K. Sugimachi, K. Funatsu

Research output: Contribution to journalArticle

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Abstract

We describe a preclinical study of our original hybrid artificial liver support system (HALSS) for a clinical trial. We designed a HALSS comprising a multi-capillary polyurethane foam packed-bed module (MC-PUF module) containing a total 200 g (2 × 1010 cells) porcine hepatocytes, and an extracorporeal circulation device. Almost all porcine hepatocytes in the MC-PUF module formed many spherical multicellular aggregates (spheroids). This extracorporeal circulation device was improved to promote solute exchange between a living body and a MC-PUF module by including a plasma bypass line in the circulation loop. The efficacy of the HALSS was evaluated using a 25-kg pig with warm ischemic liver failure by portocaval shunt and ligation of hepatic artery (HALSS group, n=3). As a control experiment, the same system without hepatocytes in the module was used with the same kind of liver failure pig (Control group, n=3). The blood ammonia in the control group was 143 N-μg/dl at the start of circulation, and rapidly increased to 351 N-μg/dl at 2 hours and to 704 N-μg/dl at 6 hours. But the blood ammonia in the HALSS group was completely suppressed, and remained less than the hepatic coma level (over 200 N-μg/dl) during the circulation time. The blood glucose in the control group gradually decreased, and became less than 40 mg/dl within 6 hours of circulation. But the blood glucose in the HALSS group was maintained well, and remained the normal glucose level (50 - 105 mg/dl) for more than 20 hours of circulation. Improvement in blood creatinine and lactate, and the stabilization of vital signs and urinary excretion, were observed in the HALSS group. The survival time of the pigs in the HALSS group was 19.3 hours compared with 8.9 hours in the control group. In conclusion, our HALSS was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that our HALSS has a strong possibility to be used in treating liver failure patients. We have applied for approval of the clinical trial of our HALSS to our institutional ethics committee.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalInternational Journal of Artificial Organs
Volume25
Issue number1
Publication statusPublished - Mar 27 2002

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Artificial Liver
Liver
Polyurethanes
Foams
Hepatocytes
Swine
Experiments
Liver Failure
Blood
Control Groups
Packed beds
Extracorporeal Circulation
Ammonia
Glucose
Blood Glucose
polyurethane foam
Cellular Spheroids
Clinical Trials
Equipment and Supplies
Ethics Committees

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

Cite this

Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment. / Nakazawa, K.; Ijima, H.; Fukuda, J.; Sakiyama, R.; Yamashita, Y.; Shimada, M.; Shirabe, K.; Tsujita, E.; Sugimachi, K.; Funatsu, K.

In: International Journal of Artificial Organs, Vol. 25, No. 1, 27.03.2002, p. 51-60.

Research output: Contribution to journalArticle

Nakazawa, K, Ijima, H, Fukuda, J, Sakiyama, R, Yamashita, Y, Shimada, M, Shirabe, K, Tsujita, E, Sugimachi, K & Funatsu, K 2002, 'Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment', International Journal of Artificial Organs, vol. 25, no. 1, pp. 51-60.
Nakazawa, K. ; Ijima, H. ; Fukuda, J. ; Sakiyama, R. ; Yamashita, Y. ; Shimada, M. ; Shirabe, K. ; Tsujita, E. ; Sugimachi, K. ; Funatsu, K. / Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment. In: International Journal of Artificial Organs. 2002 ; Vol. 25, No. 1. pp. 51-60.
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AU - Yamashita, Y.

AU - Shimada, M.

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