Enhanced Liver Regeneration After Partial Hepatectomy in Mice Treated with a Prolyl Hydroxylase Inhibitor.
1Thomas Jefferson University, Philadelphia, PA
2University of California, Berkeley, Berkeley, CA
3Lankenau Institute for Medical Research, Wynnewood, PA
Meeting: 2017 American Transplant Congress
Abstract number: A155
Keywords: Liver failure, Living-related liver donors, Mice
Session Information
Session Name: Poster Session A: Ischemic Injury and Organ Preservation Session I
Session Type: Poster Session
Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Purpose: Resection of more than 70% of liver mass increases incidence of post-operative hepatic failure due to an inability of the liver remnant to adequately regenerate. This limits use of extensive hepatectomy to treat liver tumors and in living donor liver transplantation. 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA) hydrogel has been shown to stabilize HIF-1α and induce regenerative healing in an earhole injury mouse model. In this study, we investigate the impact of DPCA on liver regeneration in a mouse hepatectomy model.
Methods: Partial hepatectomy (pHx) was performed in Swiss Webster mice at 8 to 10 weeks. The two study groups with 3 mice each were No treatment and Treatment (DPCA given at hepatectomy). Body weight prior to surgery and the mass of liver resected were measured. All mice were euthanized at 3 days and the liver remnant was weighed. Regenerated liver mass was calculated based on masses of the liver resected and the liver remnant and an estimate of initial liver mass based on non-surgery controls. Means were calculated and statistical analysis was performed using the student's t-test.
Results: Experimental data is summarized in table 1.
| Mass in grams | Control (n=3) | Treatment (n=3) | p-value |
| Initial Body Mass (BM) | 30.5 | 29.2 | 0.567 |
| Liver Mass Resected/Initial BM | 0.032 | 0.030 | 0.225 |
| Liver Mass at Euthanasia/Initial BM | 0.032 | 0.039 | 0.029 |
| Liver Mass Regenerated/Initial BM | 0.019 | 0.024 | 0.034 |
Estimated liver regeneration was significantly greater in the Treatment group (0.71g) as compared to non-treated (0.59 g). To normalize for mouse size, all measurements were divided by initial body mass. Using these ratios, liver mass at euthanasia was 0.039 for the Treatment group versus 0.032 in the Control group (p=0.029) and liver mass regenerated was 0.024 in the Treatment group versus 0.019 in the non-treated group (p=0.034).
Conclusions: We demonstrated significant enhancement in liver regeneration in mice at 3 days after partial hepatectomy with DPCA administered at pHx. This work suggests that DPCA as a potential therapeutic agent to accelerate liver regeneration, which could allow for more extensive liver resection with decreased risk of postoperative liver failure.
CITATION INFORMATION: Latona J, Shah A, Cheng J, Messersmith P, Heber-Katz E. Enhanced Liver Regeneration After Partial Hepatectomy in Mice Treated with a Prolyl Hydroxylase Inhibitor. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Latona J, Shah A, Cheng J, Messersmith P, Heber-Katz E. Enhanced Liver Regeneration After Partial Hepatectomy in Mice Treated with a Prolyl Hydroxylase Inhibitor. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/enhanced-liver-regeneration-after-partial-hepatectomy-in-mice-treated-with-a-prolyl-hydroxylase-inhibitor/. Accessed November 22, 2024.« Back to 2017 American Transplant Congress