BIOLOGY 2F03 Lecture Notes - Lecture 19: Primary Sclerosing Cholangitis, Esophageal Varices, Hepatic Encephalopathy

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Surgery and Anaesthesia Sheena Cheung ssc211
Module 1: Cancer repair and regeneration With additions from ABS notes
3
Liver stem cell transplantation
27 October 2014
08:57
Dr M Pai
Stem cell
A cell that has infinite ability to self-replicate and divide throughout the life of the organism
Unspecialised cells that renew themselves for long periods through cell division that can be
induced to become any cell with their specific function
Adult stem cells are undifferentiated found in differentiated specialised tissue: e.g.
mesenchymal stem cell in bone marrow
Difference between stem cell and PROGENITOR CELL: progenitor cell can only divide into
different specialised cells - however, a true stem cell can self replicate (divide into itself) as
well as specialised cell
Plasticity: ability of adult stem cell from one tissue to generate the specialised cell type of
another tissue
o Clinical property of stem cell to exploit
Omnicyte
Adherent CD34+ haemopoietic stem cell (1% total CD34+ cell population)
Small and lymphocyte like, high nuclear/cytoplasmic ratio
Low levels of CD38/33 and HLA-DR
Investigated mechanisms of differentiation and expansion
o Trans-differentiation: stem cells injected into the liver is influenced by factors in the
environment therefore become the equivalent mature differentiated cells by clonal
expansion of the HSC
o Fusion: injected stem cell fuses with mature hapatocyte to share genetic information,
and divide again to form mature differentiated cell
Either by nuclear fusion or cytoplasmic fusion followed by reduction division
Liver disease
Acute damage: drugs, viral (hep A & B), alcohol, AI
Chronic
o Liver cell damage: alcohol, AI, viral (hep B & C), haemochromatosis, Wilsons, a1
antitrypsin deficiency
o Biliary: Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis PSC
o Complications of cirrhosis due to high portal hypertension: ascites, SBP, hepatic
encephalopathy, oesophageal varices, hepatocellular carcinoma
Cirrhosis: 4k deaths/year, with alcohol most common and increasing hepatitis C cause (HCV
20% will develop cirrhosis, 3% develop 3%)
Definitive treatment: liver transplantation but 8% die awaiting transplant
Therefore plasticity of stem cell is hopefully going to be an alternative to liver transplantation
to bridge the gap and fill the need for more organs
Early phase trial results of stem cell treatment for liver disease
Stem cell populations mobilised into blood (via hepatic artery or portal vein) by G-CSF in
patients with chronic liver insufficiency
Investigating safety and toxicities
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Document Summary

A cell that has infinite ability to self-replicate and divide throughout the life of the organism. Unspecialised cells that renew themselves for long periods through cell division that can be induced to become any cell with their specific function. Adult stem cells are undifferentiated found in differentiated specialised tissue: e. g. mesenchymal stem cell in bone marrow. Difference between stem cell and progenitor cell: progenitor cell can only divide into different specialised cells - however, a true stem cell can self replicate (divide into itself) as well as specialised cell. Plasticity: ability of adult stem cell from one tissue to generate the specialised cell type of another tissue: clinical property of stem cell to exploit. Adherent cd34+ haemopoietic stem cell (1% total cd34+ cell population) Either by nuclear fusion or cytoplasmic fusion followed by reduction division. Acute damage: drugs, viral (hep a & b), alcohol, ai. Cirrhosis: 4k deaths/year, with alcohol most common and increasing hepatitis c cause (hcv.

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