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Hepatocyte and Islet Cell Cotransplantation on Poly-L-Lactide Matrix for the Treatment of Liver Cirrhosis
Open accessAbstract
The human autologous hepatocyte matrix implant is a promising alternative procedure to counter liver damage. We assessed the outcome of human hepatocytes isolation from cirrhotic liver compared to the clinical and histological scores of disease severity. A total of 11 patients with various clinical scores (CTP and MELD) and histological score (Metavir, fibrosis) of liver cirrhosis were included in the hepatocyte matrix implant clinical phase I study. The liver segment and pancreatic tissue were harvested from each patient, and hepatocytes and cells of islets of Langerhans were isolated. The freshly isolated human hepatocytes were coseeded with the islet cells onto poly(l-lactic acid) (PLLA) scaffolds, cultured, and transplanted back into the patient. Human hepatocytes were isolated from 11 cirrhotic liver specimens with a resulting yield of 1.4 ± 0.5 × 106 cells per gram of the liver specimen and a viability rate of 52 ± 13%. It was found that the yield and viability of the liver cells were not correlated with the clinical and histological scores of the liver cirrhosis. A correlation was found between the hepatocyte yield obtained and the average number of hepatocytes counted in 10 microscopic fields of view. More viable cells were obtained from cirrhotic livers caused by chronic hepatitis B as compared to chronic hepatitis C in the same MELD score range. There was no correlation between the clinical and histological disease severity scores of liver cirrhosis and the outcome of hepatocytes isolation. It seems that the yield could depend on the type of hepatitis underlying the cirrhotic tissue. The study was registered at www.clinicaltrial.gov with the study identifier: NCT01335568.
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“Nevertheless, unlike findings from animal experiments, human studies did not show favorable results regarding liver function, fibrosis, or survival rates [37–39].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [38]
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“In a recent clinical trial, human autologous hepatocytes were co-cultured with islet cells onto a 3D porous poly-L-lactic acid scaffold and subsequently re-implanted into the mesentery leaves of patients with LC, resulting in improved model for end-stage liver disease (MELD) scores and liver-related blood values [38].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [38]
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“However, a decline in albumin (ALB) and cholinesterase (CHE) levels toward the end of the study was noted, leading to speculation about the maintenance of cell viability and functionality.”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [38]
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Citations
Cites
Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis
Mokdad, A. A., Lopez, A. D., Shahraz, S., Lozano, R., Mokdad, A. H., Stanaway, J., Murray, C. J., & Naghavi, M. (2014) · BMC Medicine · doi:10.1186/s12916-014-0145-y · Cited by 1,129
Hippo Pathway Activity Influences Liver Cell Fate
Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857
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Cited by
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Pan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2
“…trial, human autologous hepatocytes were co-cultured with islet cells onto a 3D porous poly-L-lactic acid scaffold and subsequently re-implanted into the mesentery leaves of patients with LC, resulting in improved model for end-stage liver disease (MELD) scores and liver-related blood values [38].”
Metadata
- Authors
- Hendrawan, S., Lheman, J., Nuraeni, Weber, U., & Baer, H. U.
- Affiliations
- Tarumanagara University (ID)
- Tarumanagara Human Cell Technology Laboratory, Faculty of Medicine, Tarumanagara University, Jakarta 11440, Indonesia
- University of Bern (CH)
- Corresponding author
- Hendrawan, Siufui
- Venue
- International Journal of Hepatology
- Publisher
- Wiley
- Published
- 2020-10-13
- Volume
- 2020
- Pages
- 1-6
- ISSN
- 2090-3448 (ISSN-L)
- 2090-3456
- PMC
- PMC7582088
- OpenAlex
- W3093137305
- Cited by
- 4
- References
- 2
- Citations by year
- 2025: 3 · 2024: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Hepatology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Gading Pluit Hospital, Jakarta, Indonesia
- Tarumanagara Foundation and Tarumanagara University, Jakarta
- The Foundation for Cell Matrix Research, Zurich, Switzerland
- Baermed, Centre of Abdominal Surgery, Zurich
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver cirrhosis, hepatocyte transplantation, islet transplantation, hepatocyte isolation, poly(L-lactic acid) scaffolds, autologous cell transplantation, chronic hepatitis B, chronic hepatitis C, disease severity index, MELD score, METAVIR score
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