Project Proposal:

Organoids
By Aditya, Dean, Diamon
Our Problem: Animal Testing
Some Background
Animal testing: use of non-human
animals in experiments
Experiments test compounds that
control variables which affect
disease progression
The testing of animals raises
multiple ethical questions
The costs of testing on and
maintaining animals are extremely
high
Statistics on Animal Testing

Almost 100 million animals were killed in the U.S. last year
600,000+ animals were subjected to tests considered cruel
Approximately $16 billion spent on testing
92% of experimental drugs dont show reliable results in humans
Whats Been Done

Federal regulations (Animal Welfare Act)

This hasnt done much to reduce the harm to animals

Doesnt improve the accuracy of tests

Genetic modification to more accurately represent human models

Doesnt solve the ethical questions

Only gives little advantage in representing human systems

Federal Regulations
The U.S. currently only
has one act signed to
regulate testing
Animal Welfare Act
excludes up to 95% of
animals
Labs do not have to
report tests on
non-reported animals
Genetically Engineering Animals
DNA cloning: used to generate
copies of genes to alter research
animals
Animals are engineered to better
express disease models of humans
These include increasing
susceptibility to cancer and
inducing diseases like diabetes
Our Proposed Solution

Develop and implement the

use of organoids in field of
biomedical research.
Generate 3-D models that
represent the physiology of
human development
Allow for more accurate
observation of the responses
of cells
What Are Organoids And How Do They Work
Complex multicellular
structures generated from
stem cell cultures
Simulate the interactions
between multiple types of
cells
Developed using culturing
scaffolds with media
(Matrigels) to direct
growth
Organoids V.S. In Vitro Cells
A simple in vitro system only shows
how it works on one type of cell
An organoid could create a complex
system
Shows how the drug will affect multiple
types of cells
Also shows their interactions
How Are They Made
1. Organic tissue is broken down into sub-units with primary and
stem cells
2. These are enriched further to completely separate out the stem
cells from the tissue
3. The resulting amalgam of cells is exposed to differentiation factors
including BMP, R-Spondin, and Noggin
4. Then they are exposed to further niche factors in an extracellular
matrix that direct and sustain the growth of the organoids
This includes HGF, FGF10, and p38 inhibitors for cerebral
organoids
Our Efficacy Tests
Step 1: Induce Parkinsons in in vitro cell lines using 6-OHDA and
MPTP, two potent neurotoxins
Step 2: Develop cerebral organoids using standard procedures
described the previous slides
Step 3: Use these neurotoxins to simulate disease in the
organoids
Step 4: Compare the results in the single cell lines to the outcome
in the organoids
Step 5: Use the organoids to screen a positive control, one that
has already exhibited results in single cells
How Will This Solve Our Problem

Improves the current system of

observing and analyzing
compounds
Eliminates a large majority of
newly synthesized molecules
There would be less chances of
error in beginning stages of
testing
How It Solves Our Problem
Overall number of molecules
that have to be tested in in
vivo disease models or safety
studies will decrease
This reduces the chance of
toxic materials reaching
clinical trials
This could decrease the harms
caused to animals as well
The Financial Logistics
Costs per organoid:
Cerebral Organoids: $150 per:
Cambridge University, Lancaster et al.

Intestinal: $400 per plate of 20-30:

Cincinnati Childrens Hospital, Mah et
al.

Costs per animal:

According to NIH, $16 billion spent per
year

Purebred Beagles cost approximately

$1049, without equipment
More Logistics

Competition

Not much

Customers:

Virtually anyone on medication

This alters the way all, or at least most, compounds are tested

Benefits

Decreases ethical questions and problems

Also reduces the costs of research