Expression of liver-specific functions by rat hepatocytes seeded in treated poly( lactic-co-glycolic) acid biodegradable foams

Hasırcı, Vasıf Nejat
Bondre, SP
Gresser, JD
Trantolo, DJ
Toner, M
Wise, DL
Techniques of liver replacement would benefit patients awaiting donor livers and may be a substitute for transplantation in patients whose livers can regenerate. Poly(lactic-co-glycolic acid) (PLGA) copolymers are biodegradable and have been shown to be useful as scaffolds for seeding and culturing various types of cells. In this study, foam disks were prepared from PLGA (lactic-to-glycolic mole ratio of 85:15) by lyophilization of benzene (5% w/v) solutions. These disks were then used as scaffolds for rat hepatocyte culture. Foams were coated with either a type I collagen gel (0.1% w/v), coated with gelatin (5% w/v), or treated with oxygen plasma (25 W, 90 s) to modify their surface chemistry and wettability. The disks were then seeded with rat hepatocytes (10(6)/mL) and cultured for a period of 2 weeks. All surface treatments resulted in increased hydrophilicity, the greatest being obtained by collagen treatment (contact angle, < 10<degrees>), and a minimal decrease in void fraction (5%). DNA content after a 2-week culture period increased proportionally with the wettability of the treated foam surface. Urea synthesis in untreated foams averaged 15.3 +/- 62.3 mug/h/ mg DNA, which was significantly higher than that for controls, whereas gelatin and collagen treated foams exhibited urea synthetic rates below the control levels at all times. The DNA content decreased significantly by about 50% between days 1 and 12. PLGA foams, treated and untreated, represent a promising scaffold for scaling up hepatocyte cultures.


Optimal Liver Acceptance for Risk-Sensitive Patients
Batun, Sakine; Bhandari, Atul; Roberts, Mark S. (2018-09-01)
The only therapy for patients with end-stage liver disease is transplantation. In order to be eligible for a cadaveric liver transplantation in the United States, a patient must join a waiting list maintained by the United Network for Organ Sharing System, which allocates livers using a complex priority system. When a liver offer is made, each patient must decide whether to accept the offer. Although several other models considered this decision-making process, they maximize life expectancy rather than expe...
Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death
Lee, Eric A.; Angka, Leonard; Rota, Sarah-Grace; Hanlon, Thomas; Mitchell, Andrew; Hurren, Rose; Wang, Xiao Ming; Gronda, Marcela; Boyacı, Ezel; Bojko, Barbara; Minden, Mark; Sriskanthadevan, Shrivani; Datti, Alessandro; Wrana, Jeffery L.; Edginton, Andrea; Pawliszyn, Janusz; Joseph, Jamie W.; Quadrilatero, Joe; Schimmer, Aaron D.; Spagnuolo, Paul A. (2015-06-15)
Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic...
Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells.
Narci, Kubra; Kahraman, Deniz Cansen; Koyas, Altay; Ersahin, Tulin; Tuncbag, Nurcan; Atalay, Rengul Cetin (2022-03-24)
Background: Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targeted therapies through synergistic activities, isoform specific effects of the inhibitors are usually ignored. This study concentrated on PI3K/Akt/mTOR pathway and t...
Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance
BARAN, YUSUF; Guer, Bala; Kaya, Pelin; Ural, Ali Ugur; Avcu, Ferit; Gündüz, Ufuk (2007-12-01)
The major problem in the treatment of acute myeloid leukemia (AML) patients results from multidrug resistance to administered anticancer agents. Drug resistance proteins, MDR1 and MRP1, which work as drug efflux pumps, can mediate the multidrug resistance of human leukemia cells. In this study, the mechanisms of resistance to doxorubicin-induced cell death in human HL60 AML cells were examined.
Differential alteration of IL-8 in liver cancer stem cell enrichment in response to PI3K/Akt/mTOR inhibitors and sorafenib
Kahraman, Deniz Cansen; Kahraman, Tamer; Atalay, Rengül (2018-07-01)
Liver cancer stem cells (LCSCs) are derived from damaged and transformed hepatic progenitor cells (HPCs) during precancerous cirrhosis stage. Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways are significantly deregulated in liver cancer. The activation of PI3K/AKT/mTOR pathway in LCSC population is one of the reasons for acquired resistance to sorafenib in advanced hepatocellular carcinoma (HCC) patients. Therefore, identifying novel inhibitors targeting this pathway acting on LCSCs is highly essential. We...
Citation Formats
V. N. Hasırcı, S. Bondre, J. Gresser, D. Trantolo, M. Toner, and D. Wise, “Expression of liver-specific functions by rat hepatocytes seeded in treated poly( lactic-co-glycolic) acid biodegradable foams,” TISSUE ENGINEERING, pp. 385–394, 2001, Accessed: 00, 2020. [Online]. Available: