Stem cells in liver diseases and cancer: Recent advances on the path to new therapies

Abstract

Stem cells have potential for therapy of liver diseases, but may also be involved in the formation of liver cancer. Recently, the AASLD Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation. This report summarizes the outcomes of the conference and provides an update on recent research advances. Progress in liver stem cell research includes isolation of primary liver progenitor cells (LPC), directed hepatocyte differentiation of primary LPC and pluripotent stem cells, findings of transdifferentiation, disease-specific considerations for establishing a therapeutically effective cell mass, and disease modeling in cell culture. Tumor initiating stem-like cells (TISC) that emerge during chronic liver injury share expression of signaling pathways, including those organized around TGF-β and β-catenin, and surface markers with normal LPC. Recent investigations of the role of TISC in hepatocellular carcinoma have provided insight into the transcriptional and posttranscriptional regulation of hepatocarcinogenesis. Targeted chemotherapies for TISC are in development as a means to overcome cellular resistance and mechanisms driving disease progression in liver cancer.

Efficacy of Using Cancer Stem Cell Markers in Isolating and Characterizing Liver Cancer Stem Cells

“…According to current theory, primary liver cancers originate from either differentiated liver cells (hepatocytes) or LCSCs [25]. Common causative agents for HCC such as HCV can induce liver cancer via activation of CSC pathways [25].…”

“…Common causative agents for HCC such as HCV can induce liver cancer via activation of CSC pathways [25]. Further, currently available HCC therapies often fail because of their limited ability to kill CSCs.…”

The Potential for Immunogenicity of Autologous Induced Pluripotent Stem Cell-derived Therapies

“…Directed differentiation of PSCs into mature cell types represents a substantial challenge for the field of regenerative medicine across many therapeutic areas. There are a number of human cell types that, to date, can be differentiated only to immature phenotypes in vitro, including cardiomyocytes (19), hematopoietic stem cells (20), hepatocytes (21), and pancreatic ␤-cells (22). An immature phenotype poses two risks for immune response, the first being low MHC class I (MHC-I) expression.…”

Surface markers of liver cancer stem cells and innovative targeted-therapy strategies for HCC (Review)

“…Traditional therapy strategies currently available for HCC include surgical procedures, radioactive particle implantation, radiofrequency ablation, hepatic artery chemoembolization (TACE), and chemotherapeutics. Recent studies have indicated that these therapy strategies are still not fully efficient and have multiple drawbacks, including post-treatment relapse, chemotherapy drug resistance and metastasis (1)(2)(3)(4)(5). Thus, discovering approaches to avoid recurrence and metastasis of liver cancer and to provide novel therapeutic strategies is of outmost importance in HCC.…”