Flashcards in In Vitro Models of Disease Deck (25):
What are the models for disease?
A model demonstrates a particular COMPONENT of a disease
Cellular models (in vivo, ex vivo)
animal models (in vivo)
Human tissue / cells (in vitro)
Why does someone want to use disease models?
- Understand disease pathogenesis (mostly end stage pathogenesis, early stage would be better)
- Identification of new drug targets
- Test new drugs (efficacy and toxicity)
Whats the pathway of drug development?
- Discovery/ Drug development
- Preclinical testing including:
- In vitro, ex vitro (cell models)
- in vivo (animal models)
- in silico (computer based models
- Regulatory approval
- clinical trials
- Human treatment
What does an in vitro model need to do?
- Be a representative model of disease
- Identification and validation of new targets
- Effectiveness of new therapies
- prerequisite to clinical trials
- Find a gold standard disease model
What can be used for in-vitro models?
- Immortalised cell lines (most common)
- Primary human cells
- Human embryonic stem cells
- Cell reprogramming (induced pluripotent stem cels (iPS)
- Human organoids ( ex-vivo)
What are immortalized cell lines?
Definition: A population of cells from a tissue source that would not normally proliferate indefinitely but due to a mutation (natural or intentional) they keep undergoing division
Whats some examples of immortalized cell lines?
Hela cell line (cancer)
PC12 cell line (embryonic neural crest)
Whats the advantages of immortalized cell lines?
Continuous supply of cells
Easy to culture and manipulate
What are the disadvantages of immortalized cell lines?
- Do not act like real human cells
- No human variability (epigenetics)
- Not a real disease model
(PC12 = rat cells for modelling parkinsons)
( SH-5Y5Y cell modelling parkinsons = neuroblastoma/ cancer)
What are primary cells?
Isolated cells from human tissues i.e heart, lung, blood but not all tissues i.e brain cells
Whats a hindrance of primary cells?
Limited life span
Whats a good about primary cells?
- Primary cells more closely mimic the physiological state of cells in-vivo and generate more relevant data representing living systems i.e
- human cells
- may be disease i.e cancerous cells
- Isolated from human tissue
Whats bad about primary cells?
- Hard to culture
- Limited life span
What are human embryonic stem cells?
- Continue to undergo either sym or Asym division
- Able to generate other tissue in the body
- Obtained from a blastocyst
Can HES cells model disease?
- They may come with disease
- Can introduce the disease through mutation (genetic manipulation)
What is cell reprogramming?
Induced pulripotent stem cells
How does IPS work?
Able to use skin from patients to generate a model with parkinsons disease through genetic manipulation?
Why use skin in IPS?
Skin contains fibroblasts which express genes for
- Oct 3/4
- COX 2
- KLF 4
What does pluripotent mean?
- Continue to undergo division
- Able to generate all tissues in the body
Whats some advantages of IPS?
-More ethical that HES
-Know patients clinical details and can model the patients disease
What are the uses of IPS?
Model human disease
- Live human tissues
- Variability, epigenetics
Identify new drug targets
test new drugs (efficacy, toxicity)
Tests can be done at any stage of disease developemtn (great!)
Whats the chance a developing drug will fail during clinical trials?
80% of drug fail during clinical trials
This is because each patient has variability (unique factors) Therefore models need to have variability and human qualities
Whats the disadvantages of IPS?
- Long time to generate mature cells (~3 months)
- Low Yeild
- Variability leads to large errors in data and can lead to no statistical evidence, however if the drugs work then it works for a lot of people.
What are human organoids?
3D organs generated from human pluripotent stem cells.
- cells align correctly as would in vivo
- alllows proper cell connection