6 - Cell Therapy to Treat Liver Disease Flashcards
How much has liver disease increased by since 1970
400%
LIver functions
- Prevents shortages of nutrients by storing vitamins minerals and sugar
- Produces most proteins needed by the body
- Produces bile, a compound needed to digest fat and absorb vitamins
- Produces substances that regulate blood clotting
- Helps the body fight infection by removing bacteria
- Removes toxins
- Breaks Down nutrients from food to produce energy
LIver lobule
- Blood from portal vein and the hepatic artery flows towards central vein between hepatocytes through the sinusoids
- Bile produced by hepatocytes is collected into bile ducts bia the bile canaliculi
- Sinusoids are lined with endothelial cells
Kupffer cells
- Resident macrophages of the liver
- Located at the luminal side of sinusoids
Canal of hering
The junctional region between hepatocytes and bile ducts
Regeneration of liver cells
- Gut derived factors (e.g. LPS) are upregulated, activating hepatic non parenchymal cells increasing the production of TNF and IL-6
- Other factors are released that allow the hepatocytes to overcome cell cycle checkpoint controls and move through cell cycle
- TGF is blocked
Transforming growth factor (TGF)
Inhibits hepatocyte DNA synthesis
Other factors released that allow hepatocytes to overcome cell cycle checkpoint controls
- Pancreas (insulin)
- Duodenum
- Salivary gland (EGF)
- Adrenal gland (norepinephrine)
- Thyroid gland (T4)
Cholangiocytes
- Epithelial cells of the bile duct.
- Derived from hepatoblasts /oval cells
- Peak of proliferation occurring a few hours after hepatocytes
Liver sinusoidal endothelial cells (LESCs)
- Lasts several days - weeks
- Includes precursors that migrate from the bone marrow
Kupffer cells and immune cells
Local proliferation of Kupffer cells plus migration of
mononuclear cells from the blood
Hepatic stellate cells
- Not well understood
- Synthesise components of the extracellular matrix
- Produce signalling molecules essential for liver regeneration
Hepatic stem/progenitor cell (oval cells)
- Bipotential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic and the cholangiocytic lineages.
- Resides in canal of Hering
Canals of Hering
Represent the smallest and most peripheral branches of the biliary tree connecting the bile canalicular system
with interlobular bile ducts
Stem/progenitor cells under normal physiological conditions
Homeostasis is achieved predominantly by
proliferation of mature hepatocytes.
Stem/progenitor cells under injury conditions
Results in extensive reprogramming of hepatocytes and cholangiocytes, activation and differentiation of LPCs, immune infiltration, and formation of several
intermediate cell types expressing markers of hepatocytes, cholangiocytes,