11. Cell Therapy - Prospects for Treating Liver Disease Flashcards
What can cause liver disease?
Genetics
- Blood proteins
- Inborn errors of metabolism
Lifestyle
- Booze
- Obesity
What is the only current treatment for liver disease?
Liver transplant
What is cell therapy?
Introduction of cells into tissues of an organism to treat disease
How can gene therapy include cell therapy?
Genes transplanted into cells, then cells returned to organism
What is the oldest and safest form of cell therapy?
Blood transfusion
Bone marrow transplant
What is the bystander effect of transplanted cells?
Do need to replace defective cells
Transplant cells that enhance function of defective cells
e.g. mesenchymal cells enhance cardiomyocyte function
What type of stem cells are used for therapy?
Adult progenitor cells (divide finite number of times)
Adult Stem Cells
- Tissue specific
- Multipotent adult progenitor cells (MAPC)
- Adult mesenchymal stem cells
Embryonic stem cells
Induced pluripotent stem cells (iPSC)
What are the advantages of using progenitor cells?
Close to cell of interest
Requires little manipulation
Grows well
Reduced possibility of becoming a very different cell
Reduced possibility of becoming cancerous
What is a reporter gene?
Gene that produces a recordable substance, “reports” that gene of interest is working/turned on etc
What is the process for generating liver from liver progenitor cells?
Get LPCs from mice
Generate LPCs with reporters to allow tracing of genes
- GFP, EGFP, LacZ
Generate LPCs with reporters that signal differentiation into functional hepatocytes
- TAT-lacZ LPCs
From petri dish to patient, how are LPCs generated and transplanted?
Liver cells selected and expanded
LPCs taken and genes checked
Functionally restored LPCs differentiate into funcional hepatocytes
Transplanted
What is methylmalonyl Aciduria (MMA)?
Inborn error of metabolism - functional defect in methylmalonyl CoA mutase
1:25-50000
Toxic MMA accumulation
Need liver transplant
What is OTC deficiency?
Ornithine Transcarbamylase Deficiency
Causes build up of ammonia
- Brain damage
- Seizures
- LethargyWhat is the strategy/process for OTC treatment?
Fibroblasts reprogrammed to iPSCs
iPSCs differentiated to LPCs
LPCs genetically altered - function restored to LPCs
Differentiate to hepatocytes - Functionally restored
What gene is being corrected, and how is it being corrected in treatment of OTC?
Exon 4 defect AAV vector (adeno-associated virus) SPFash is name of gene?
