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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)
SH-5Y5Y (neuroblastoma)


Whats the advantages of immortalized cell lines?

Continuous supply of cells
limited variability
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?

They are:
- 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
Investigate pathogenesis
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.

3D structure
- cells align correctly as would in vivo
- alllows proper cell connection

organs generated
- liver
- pancreas
- gut
- brain


Whats the gold standard of disease models?


= Drug and target indentification
= genetic testing
= variability = success