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Novel methods for the treatment of liver fibrosis using in vivo direct reprogramming technology
- Publication Year :
- 2016
- Publisher :
- AME Publishing Company, 2016.
-
Abstract
- Liver fibrosis, a form of scarring, gradually develops in chronic liver diseases when hepatocyte regeneration cannot compensate for hepatocyte death. At earlier stages, collagen produced by activated myofibroblasts (MFs) functions to maintain tissue integrity, but upon repeated injury, collagen accumulation suppresses hepatocyte regeneration, ultimately leading to liver failure. As a strategy to generate new hepatocytes and limit collagen deposition in the chronically injured liver, we developed in vivo reprogramming of MFs into hepatocytes using adeno-associated virus (AAV) vectors expressing hepatic transcription factors. We first identified the AAV6 subtype as effective in transducing MFs in mouse models of chronic liver disease. We then use lineage-tracing approaches to show that hepatocytes reprogrammed from MFs replicate primary hepatocyte function, and that liver fibrosis in AAV treated animals is reduced. Because AAV vectors are already used for liver-directed human gene therapy, our strategy has potential for clinical translation into a therapy for liver fibrosis.
- Subjects :
- 0301 basic medicine
Liver Cirrhosis
Pathology
medicine.medical_specialty
Cirrhosis
Liver fibrosis
Hepatitis C virus
Mice, Transgenic
010501 environmental sciences
medicine.disease_cause
01 natural sciences
Models, Biological
Article
Extracellular matrix
03 medical and health sciences
In vivo
Fibrosis
medicine
Animals
Cell Lineage
Myofibroblasts
0105 earth and related environmental sciences
Oligonucleotide Array Sequence Analysis
Hepatitis B virus
Mice, Inbred BALB C
Cholestasis
Integrases
business.industry
Dependovirus
Dicarbethoxydihydrocollidine
medicine.disease
Cellular Reprogramming
030104 developmental biology
Liver
Cancer research
Commentary
Hepatocytes
business
Reprogramming
Biomarkers
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....a19d4e9001c07010b1a30d06bc14ee43