851 ACTIVATION OF PROGENITOR CELLS TRIGGERS THE REPOPULATION OF CONDITIONAL NEMO KO LIVERS DURING LIVER REGENERATION IN MICE

2009 ◽  
Vol 50 ◽  
pp. S310
Author(s):  
Y. Malato ◽  
N. Beraza ◽  
N. Gassler ◽  
M. Al-Masaoudi ◽  
C. Liedtke ◽  
...  
Stem Cells ◽  
2017 ◽  
Vol 35 (4) ◽  
pp. 920-931 ◽  
Author(s):  
Norihisa Ichinohe ◽  
Masayuki Ishii ◽  
Naoki Tanimizu ◽  
Junko Kon ◽  
Yusuke Yoshioka ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jacquelyn O. Russell ◽  
Sungjin Ko ◽  
Satdarshan P. Monga ◽  
Donghun Shin

Liver regeneration after most forms of injury is mediated through the proliferation of hepatocytes. However, when hepatocyte proliferation is impaired, such as during chronic liver disease, liver progenitor cells (LPCs) arising from the biliary epithelial cell (BEC) compartment can give rise to hepatocytes to mediate hepatic repair. Promotion of LPC-to-hepatocyte differentiation in patients with chronic liver disease could serve as a potentially new therapeutic option, but first requires the identification of the molecular mechanisms driving this process. Notch signaling has been identified as an important signaling pathway promoting the BEC fate during development and has also been implicated in regulating LPC differentiation during regeneration. SRY-related HMG box transcription factor 9 (Sox9) is a direct target of Notch signaling in the liver, and Sox9 has also been shown to promote the BEC fate during development. We have recently shown in a zebrafish model of LPC-driven liver regeneration that inhibition of Hdac1 activity through MS-275 treatment enhances sox9b expression in LPCs and impairs LPC-to-hepatocyte differentiation. Therefore, we hypothesized that inhibition of Notch signaling would promote LPC-to-hepatocyte differentiation by repressing sox9b expression in zebrafish. We ablated the hepatocytes of Tg(fabp10a:CFP-NTR) larvae and blocked Notch activation during liver regeneration through treatment with γ-secretase inhibitor LY411575 and demonstrated enhanced induction of Hnf4a in LPCs. Alternatively, enhancing Notch signaling via Notch3 intracellular domain (N3ICD) overexpression impaired Hnf4a induction. Hepatocyte ablation in sox9b heterozygous mutant embryos enhanced Hnf4a induction, while BEC-specific Sox9b overexpression impaired LPC-to-hepatocyte differentiation. Our results establish the Notch-Sox9b signaling axis as inhibitory to LPC-to-hepatocyte differentiation in a well-established in vivo LPC-driven liver regeneration model.


Apmis ◽  
2005 ◽  
Vol 113 (11-12) ◽  
pp. 876-902 ◽  
Author(s):  
ERIC SANTONI-RUGIU ◽  
PETER JELNES ◽  
SNORRI S. THORGEIRSSON ◽  
HANNE CATHRINE BISGAARD

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
D Sabry ◽  
W A Khalifa ◽  
M M Abdelgwad ◽  
M Alhelf ◽  
Z M Altaib

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) and human umbilical cord endothelial progenitor cells (UC-EPCs) have several benefits for liver regeneration. We speculate huge impacts of rat BM-MSCs and UC-EPCs on reversal of hepatic injury and improvement of liver function in liver fibrosis induced by carbon tetrachloride (CCl4). Methods Forty adult rats were divided into 4 groups; control group, CCl4 group, CCl4/BM-MSCs group and CCl4/UCEPCs group. Blood samples were driven from rats at 1, 2 and 3months to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of HGF,TGF-β, MMP-2, and VEGF were assessed by polymerase chain reaction. Histological examination of the liver tissue was performed. α-SMA immunohistochemistry to identify the myoepithelial cells (MECs) and Ki-67 to identify cell prolifration immunohistochemistry are detected in groups injected with cells to confirm cells regeneration. Results Regarding liver function, there was elevating albumin (P < 0.05) and reducing ALT (P < 0.05) concentrations in groups treated with BM-MSCs and UC-EPCs effect compared to untreated CCL4 group. Concerning gene expression, UC-EPCs treated group have significantly higher MMP-2 and VEGF (P < 0.01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BM-MSCs in increasing gene expression of HGF (P < 0.05) and immunohistochemistry of α-SMA and Ki-67 (P < 0.01). BM-MSCs have significantly lower TGF- β (P < 0.00) compared to UC-EPCs. Conclusion This study highlighted on liver regeneration role of both human UC-EPCs and BM-MSCs in liver fibrosis by different signaling mechanistic.


2016 ◽  
Vol 161 (1) ◽  
pp. 155-161 ◽  
Author(s):  
A. V. El’chaninov ◽  
T. Kh. Fatkhudinov ◽  
E. Yu. Kananykhina ◽  
N. Yu. Usman ◽  
I. V. Arutyunyan ◽  
...  

2018 ◽  
Vol 2 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Irina G. Danilova ◽  
Hanna Kalota ◽  
Musa T. Abidov

Effective drug therapy promoting liver regeneration is a challenging goal in pharmacotherapy of liver diseases. Several plant phytochemicals recommended in traditional medicine from over hundred plants have been investigated for its use in various liver disorders. Regeneration of injured liver depend on a proliferative potential of mature hepatocytes as well as different subsets of intrahepatic and extrahepatic stem/progenitor cells. In clinical trials a stem cell therapy resulted in a limited improvement of liver functions. Animal studies have demonstrated the involvement of bone marrow-derived stem/progenitor cells in liver regeneration. For this reason, the pharmacological activation of endogenous stem cells and pharmacological control of macrophage phenotypic polarization could be an effective method of mobilizing progenitor cells to injured liver.


Cytotherapy ◽  
2011 ◽  
Vol 13 (2) ◽  
pp. 135-144 ◽  
Author(s):  
Francesco Paolo Russo ◽  
Maurizio Parola

Sign in / Sign up

Export Citation Format

Share Document