Development of a decellularized liver matrix-based nanocarrier for liver regeneration after partial hepatectomy

Chiu, Yu-Chuan; Huang, Kai-Wen; Lin, Yong-Heng; Yin, Wei-Rong; Hou, Yung-Te

doi:10.1007/s10853-023-08971-w

Cited by 3 publications

(10 citation statements)

References 76 publications

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“…However, the albumin synthesis in MHs and SHs increased by 1.38-fold (day 3) and almost 9.63-fold (day 7), respectively, in the TA-containing group ( Figure 2 B,E). These findings align with observations reported in prior studies [ 15 , 33 ].…”

Section: Discussionsupporting

confidence: 93%

“…However, no significant differences were observed on day 4 between these groups. Although TA has demonstrated benefits for MH culture, the occurrence of epithelial-to-mesenchymal transition (EMT) within 5 days of culturing can hinder hepatocyte growth and function for extended periods, even under favorable conditions [ 15 ]. In addition, Chiu et al reported that the effect of EMT was more significant within the 5 day culture period compared with that of TA [ 14 ], which is consistent with our findings ( Figure 2 B,C).…”

Section: Resultsmentioning

confidence: 99%

“…In the curative model, the relative cell viability and albumin synthesis were 0.36-fold and 3.55-fold higher, respectively, in the [TA + (APAP-SHs) + TA] group than in the APAP-SHs group ( Figure 3 E,F). The MTT assay does not only reflect cell viability but also cell proliferation [ 15 , 31 ]. Previous studies have indicated an inverse relationship between cell proliferation and differentiation [ 15 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…The MTT assay does not only reflect cell viability but also cell proliferation [ 15 , 31 ]. Previous studies have indicated an inverse relationship between cell proliferation and differentiation [ 15 , 32 ]. In addition, SHs exhibited a superior ability to maintain 3D structures and resist differentiation into fibroblast-like cells compared with MHs [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tannic acid (TA), which is primarily found in various plants used as food and feed, such as food grains, fruits, wine, and tea [ 13 , 14 ], is a natural polyphenol with diverse therapeutic properties, including antioxidant, antitumor, and anti-inflammatory effects [ 15 ]. The hepatoprotective effects of TA on APAP-induced hepatotoxicity were previously investigated due to its anti-oxidation, anti-inflammation, and anti-apoptosis properties.…”

Section: Introductionmentioning

confidence: 99%

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Prospective Application of Tannic Acid in Acetaminophen (APAP)-Induced Acute Liver Failure

Lin,

Hou

2023

IJMS

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This study investigated the effect of tannic acid (TA), a natural plant-derived polyphenol, on hepatocyte viability and function, focusing on both hepatoprotective and hepatocurative aspects within liver failure models. In an in vitro prevention model, the TA-containing group exhibited 1.5-fold and 59-fold higher relative cell viability and albumin synthesis, respectively, in injured mature hepatocytes (MHs) and 1.14-fold and 1.10-fold higher values in injured small hepatocytes (SHs), compared with the TA-free group. In the in vitro curative model, the TA-containing group exhibited 3.25-fold and 113-fold higher relative cell viability and albumin synthesis, respectively, in injured MHs and 0.36-fold and 3.55-fold higher values in injured SHs, compared with the TA-free group. In the in vivo disease model, the administration of 300 μL of 1 μg/mL TA significantly mitigated acute liver failure damage and post-APAP toxicity in mice. This was evident in serum analysis, where the levels of alanine transaminase, aspartate aminotransferase, and total bilirubin notably decreased, in agreement with histological observations. The study findings reveal that TA can enhance hepatic function at specific additive concentrations. Furthermore, even when injured by APAP, hepatocytes could revert to their preinjury state after additional TA supplementation. Additionally, pretreating hepatocytes with TA can alleviate subsequent damage. Thus, TA holds clinical potential in the treatment of APAP-induced liver failure.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prospective Application of Tannic Acid in Acetaminophen (APAP)-Induced Acute Liver Failure

Lin,

Hou

2023

IJMS

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Fabrication of a decellularized liver matrix–based hepatic patch for the repair of CCl4‐induced liver injury

Wu,

Hsieh,

Yin

et al. 2024

Biotechnology Journal

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This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin–complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin–DLM patches effectively mitigated CCl4‐induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin–DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin–DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin–complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.

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Self‐Healing Hydrogel Containing Decellularized Liver Matrix and Endothelial Cell‐Covered Hepatocyte Spheroids for Rescue of Injured Hepatocytes

Chou,

Cheng,

Yin

et al. 2024

Macromolecular Bioscience

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Liver fibrosis occurs in many chronic liver diseases, while severe fibrosis can lead to liver failure. A chitosan‐phenol based self‐healing hydrogel (CP) integrated with decellularized liver matrix (DLM) is proposed in this study as a 3D gel matrix to carry hepatocytes for possible therapy of liver fibrosis. To mimic the physiological liver microenvironment, DLM is extracted from pigs and mixed with CP hydrogel to generate DLM‐CP self‐healing hydrogel. Hepatocyte spheroids coated with endothelial cells (ECs) are fabricated using a customized method and embedded in the hydrogel. Hepatocytes injured by exposure to CCl4‐containing medium are used as the in vitro toxin‐mediated liver fibrosis model, where the EC‐covered hepatocyte spheroids embedded in the hydrogel are co‐cultured with the injured hepatocytes. The urea synthesis of the injured hepatocytes reaches 91% of the normal level after 7 days of co‐culture, indicating that the hepatic function of injured hepatocytes is rescued by the hybrid spheroid‐laden DLM‐CP hydrogel. Moreover, the relative lactate dehydrogenase activity of the injured hepatocytes is decreased 49% by the hybrid spheroid‐laden DLM‐CP hydrogel after 7 days of co‐culture, suggesting reduced damage in the injured hepatocytes. The combination of hepatocyte/EC hybrid spheroids and DLM‐CP hydrogel presents a promising therapeutic strategy for hepatic fibrosis.

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Development of a decellularized liver matrix-based nanocarrier for liver regeneration after partial hepatectomy

Cited by 3 publications

References 76 publications

Prospective Application of Tannic Acid in Acetaminophen (APAP)-Induced Acute Liver Failure

Prospective Application of Tannic Acid in Acetaminophen (APAP)-Induced Acute Liver Failure

Fabrication of a decellularized liver matrix–based hepatic patch for the repair of CCl4‐induced liver injury

Self‐Healing Hydrogel Containing Decellularized Liver Matrix and Endothelial Cell‐Covered Hepatocyte Spheroids for Rescue of Injured Hepatocytes

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