Therapeutic Potential of Plasma Proteins Derived from Umbilical Cord Blood for Acute Liver Failure.
Yu-Jen HuangChih-Yuan LeeJerry CaoHsuan-Shu LeeChih-Hao ChangPo-Da ChenYao-Ming WuPublished in: Molecular pharmaceutics (2019)
There are very limited clinically viable treatment options for acute liver failure, a life-threatening condition that rapidly progresses to loss of liver function. In this study, we aim to evaluate the therapeutic potential of UCBP for acute liver failure induced in a rat model by D-galactosamine (GalN). F344 rats were randomly divided into two groups (control and UCBP-treated) after GalN injection. The therapeutic effects of UCBP were evaluated based on survival rate, H&E staining, TUNEL, PCNA staining, and in vivo BrdU labeling. Hepatocyte proliferation and the therapeutic mechanisms of UCBP were examined with BrdU and Western blot assay in vitro. The survival rate in the UCBP-treated group was found to be increased compared to the control group (85 vs 55%, P = 0.029). UCBP treatment significantly decreased apoptosis and increased cell proliferation. These effects may be secondary to specific bioactive molecules in UCBP. In vitro experiments revealed that adiponectin is one of the key biologically active components of UCBP in facilitating this result and promoting hepatocyte proliferation. Furthermore, this effect is mediated by p38/ERK mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, this uncomplicated and clinically accessible approach may serve as effective bridge therapy for acute liver failure.
Keyphrases
- liver failure
- hepatitis b virus
- signaling pathway
- cell proliferation
- pi k akt
- umbilical cord
- mesenchymal stem cells
- oxidative stress
- liver injury
- drug induced
- type diabetes
- single cell
- insulin resistance
- high throughput
- epithelial mesenchymal transition
- cell cycle arrest
- protein kinase
- smoking cessation
- endothelial cells
- aortic dissection