Liver stem cells (LSCs) are precursors of hepatoblasts, which are presumed to be the transit-amplifying cells that first give rise to committed progenitors, and then to hepatocytes and cholangiocytes. Liver stem/progenitor cells appear and undergo a massive expansion in chronic liver damage and become cancer stem cells (CSC) to further initiate tumor formation. These cells are also known to be responsible for tumor relapse, metastasis, and chemoresistance in liver cancer. Therefore, understanding how they form, how they are sustained and how to defeat them is among the most intensive areas of cancer research today. Additionally, liver stem/ progenitor cells are candidates for ex-vivo liver cell replacement as an alternative method to orthologous liver transplantation in the treatment of end-stage liver pathologies. Recent advances allow us to obtain patient’s hepatocytes derived from inducible pluripotent stem cells (iPSCs) reprogrammed from his own fibroblast and use them for tissue replacement and gene therapy. The first step of hepatic development from iPSCs is the induction of definitive endoderm containing liver stem/progenitor cells by using chemicals. Further treatment with some growth factors can then direct cells towards the hepatic lineage. Even if the limitations of technology still remain (i.e., the potential for teratoma formation and low efficiency), iPS-derived hepatocytes are a very promising population for cell therapies in hepatology.
Soheil Akbari, Gulben Gurhan Sevinc, Nevin Ersoy, Onur Başak, Kübra Kaplan, Kenan Sevinç, Erkin Özel, Berke Sengun, Eray Enustun, Burcu Özçimen, Alper Bağrıyanık, Nur Arslan, Tamer Onder, Esra Erdal. Robust, long-term culture of endoderm derived hepatic organoids (eHEPOs) for disease modeling. Stem Cell Reports. 2019 September. doi:10.1016/j.stemcr.2019.08.007.
Delman M, Avcı ST, Akçok İ, Kanbur T, Erdal E, Çağır A. Antiproliferative activity of (R)-4'-methylklavuzon on hepatocellular carcinoma cells and EpCAM+/CD133+ cancer stem cells via SIRT1 and Exportin-1 (CRM1) inhibition. European Journal of Medicinal Chemistry. 2019 October; 180: 224-237. doi:10.1016/j.ejmech.2019.07.024.
Yavuz Tokgöz, Cahit Barış Erdur, Soheil Akbari, Tuncay Kume, Oya Sayin, Semiha Terlemez, Esra Erdal, Nur Arslan. Adipokine levels and perilipin gene polymorphisms in obese Turkish adolescents with non- alcoholic fatty liver disease . Erciyes Med J. 2018 ; 43618. doi:10.5152/etd.20 18.0010.
Büyüköz M, Erdal E, Alsoy Altinkaya S. Nanofibrous gelatin scaffolds integrated with NGF-loaded alginate microspheres for brain tissue engineering. J Tissue Eng Regen Med. 2018 February; 12 (2): e707-e719. doi:10.1002/term.2353.
Aysim Gunes, Ezgi Bagirsakci, Evin Iscan, Gulcin Cakan-Akdogan, Umut Aykutlu, Serif Senturk, Gunes Ozhan, Esra Erdal, Deniz Nart, Funda Yilmaz Barbet, Nese Atabey. Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma. Oncotarget. 2018 ; 9 (96): 36849-36866. doi:10.18632/oncotarget.26402.
. Role of Albumin in growth inhibition in Hepatocellular Carcinoma. Oncology. 2017 May; 93 (2): 136-142. doi:10.1159/000471807.
İşcan E, Güneş A, Korhan P, Yılmaz Y, Erdal E, Atabey N. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells. J Cell Commun Signal. 2017 June; 11 (2): 155-166. doi:10.1007/s12079-016-0368-0.
Tokgöz Y, Işık IA, Akbari S, Kume T, Sayın O, Erdal E, Arslan N. Perilipin polymorphisms are risk factors for the development of obesity in adolescents? A case-control study. Lipids in health and disease. 2017 March; 16 (1): 52. doi:10.1186/s12944-017-0440-7.
Sebastian Ocklenburg, Ceren Barutçuoğlu, Adile Öniz Özgören, Murat Özgören, Esra Erdal, Dirk Moser, Judith Schmitz, Robert Kumsta and Onur Güntürkün . The Genetics of Asymmetry: Whole Exome Sequencing in a Consanguineous Turkish Family with an Overrepresentation of Left-Handedness. Symmetry. 2017 May; 9 (5): 66. doi:10.3390 /sym90 50066.
Firtina Karagonlar Z, Koç D, Şahin E, Avci ST, Yilmaz M, Atabey N, Erdal E. Effect of adipocyte-secreted factors on EpCAM+/CD133+ hepatic stem cell population.. Biochemical and biophysical research communications. 2016 January; 474 (3): 482-490. doi:10.1016/j.bbrc.2016.04.137.
Firtina Karagonlar Z, Koc D, Iscan E, Erdal E, Atabey N. Elevated hepatocyte growth factor expression as an autocrine c-Met activation mechanism in acquired resistance to sorafenib in hepatocellular carcinoma cells.. Cancer science. 2016 January; 107 (4): 407-16. doi:10.1111/cas.12891.
Yilmaz Y, Atabey N, Erdal E & Brian I. Carr. Platelets, Microenvironment and Hepatocellular Carcinoma. Biochemistry & Analytical Biochemistry. 2016 June; 5: 281. doi:10.4172/2161-1009.1000281.