Therapeutic effects of hepatocyte growth factor-overexpressing dental pulp stem cells on liver cirrhosis in a rat model

Abstract

Cirrhosis is the terminal stage of hepatic diseases and is prone to develop into hepatocyte carcinoma. Increasing evidence suggests that the transplantation of dental pulp stem cells (DPSCs) may promote recovery from cirrhosis, but the key regulatory mechanisms involved remain to be determined. In this study, we overexpressed human hepatocyte growth factor (hHGF) in primary rat DPSCs and evaluated the effects of HGF overexpression on the biological behaviors and therapeutic efficacy of grafted DPSCs in cirrhosis. Liver cirrhosis was induced via the intraperitoneal injection of CCl4 twice weekly for 12 weeks and was verified through histopathological and serological assays. HGF was overexpressed in DPSCs via transduction with a hHGF-lentiviral vector and confirmed based on the elevated expression and secretion of HGF. The HGF-overexpressing DPSCs were transplanted into rats intravenously. The HGF-overexpressing DPSCs showed increased survival and hepatogenic differentiation in host liver tissue at 6 weeks after grafting. They also exhibited a significantly greater repair potential in relation to cirrhosis pathology and impaired liver function than did DPSCs expressing HGF at physiological levels. Our study may provide an experimental basis for the development of novel methods for the treatment of liver cirrhosis in clinical practice.

Epigenetic Regulation of Dental Pulp Stem Cell Fate

“…Moreover, DPSCs in prevascularized, scaffold-free, microtissue spheroids can successfully regenerate vascular dental pulp-like tissue, which provides a new strategy for endodontic treatment and makes dentin-pulp regeneration possible [ 85 ]. The clinical application potential of DPSCs is not only in dentistry but also in treatments for other diseases, such as craniofacial bone defects [ 86 ], muscle regeneration [ 87 ], myocardial infarction [ 88 ], Alzheimer's disease [ 89 ], nervous system injuries [ 90 ], Parkinson's disease, diabetes [ 91 ], stress urinary incontinence [ 80 ], osteoarthritis [ 92 ], and liver diseases [ 93 ].…”

Perspective of placenta derived mesenchymal stem cells in acute liver failure

“…The definition of MSCs according to International Society for Cell Therapy (ISCT) is as follows: MSCs are (1) able to bind plastic surfaces, (2) able to differentiate into all three classes of chondrocytes, adipocytes and osteocytes in vitro, and (3) capable of expressing CD73, CD90, and CD105 markers but not hematopoietic markers like CD45, CD14, CD19, CD34, and HLA-DR [71]. MSCs release numerous factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF), nerve growth factor (NGF), Transforming growth factor beta-1 (TGF-b1), placental growth factor (PGF), stromal cell-derived factor 1 (SDF-1/CXCL12), monocyte chemoattractant protein-1 (MCP 1/CCL2), hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, IL-10, IL-13, G-CSF and GM-CSF [72][73][74][75].…”

Human Dental Pulp Stem Cells – A Prospective Regenerative Therapy

“…The effectiveness and productivity of such kind of in vivo gene therapy highly depends on the vitality of the remaining dental pulp cells. Ex vivo gene therapy, involving the transfer of in vitro transfected cells back in vivo, may provide a better remedy (14,29,31).…”