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Comparison of 3D PCL scaffold model with traditional 2D model in the HTS system for anti-cancer drug development

Friberg, Nathalie (2021) MOBK01 20211
Degree Projects in Molecular Biology
Popular Abstract
Can we beat cancer with 3D?

In 2020, 19.3 million new cancer cases were reported, and 10 million people died from cancer. Cancer happens because of a mutation in the DNA that leads to uncontrolled cell division, eventually leading to tumors. There is much need for anti-cancer drugs, however, many potential anti-cancer drugs don’t get accepted because of being too toxic or not being good enough. The development is expensive, time-consuming and many animals suffer

When developing a new drug, the first goal is to find a target in the cell. In the second step, we want to find a chemical that hits that target, like an arrow that hits a target. To find new chemicals a method called high throughput screening (HTS) is used. HTS works by... (More)
Can we beat cancer with 3D?

In 2020, 19.3 million new cancer cases were reported, and 10 million people died from cancer. Cancer happens because of a mutation in the DNA that leads to uncontrolled cell division, eventually leading to tumors. There is much need for anti-cancer drugs, however, many potential anti-cancer drugs don’t get accepted because of being too toxic or not being good enough. The development is expensive, time-consuming and many animals suffer

When developing a new drug, the first goal is to find a target in the cell. In the second step, we want to find a chemical that hits that target, like an arrow that hits a target. To find new chemicals a method called high throughput screening (HTS) is used. HTS works by scanning chemicals to find that arrow. HTS is an in vitro method, in vitro meaning “in glass,” which means that experiments are not done on animals. It’s instead done on cell lines in so-called multi-well plates. In these wells, cells are grown and chemicals in different concentrations are tested to find new drugs.

The problem with HTS is that it’s done in a two-dimensional structure. So, what is a 2D structure, and why is it a problem? In a 2D structure the cells grow flat on the bottom of the wells, which can be seen in the schematic image bellow. They stick to the bottom with the help of proteins called integrins. However, this is a problem since the human body is not a 2D flat structure, rather it is a three-dimensional structure with bones and tissue. In the tissue, the cells can build a 3D structure by holding on to something called the extracellular matrix (ECM). The ECM consists of proteins that the cells adhere to with the help of the integrins previously mentioned.

So how can we solve this problem? We can grow the cells in a 3D structure instead, as seen in the schematic image above. The cells can be grown in a synthetic ECM made of the medically approved plastic polycaprolactone (PCL). The PCL-matrix is put in the wells, and instead of adhering to the bottom, the cells can adhere with the integrins to the PCL fibers. A microscope image of the cells in the PCL fiber can be seen to the right

When comparing the cells in the 2D and 3D, the 3D cells are more tolerant towards the chemicals and better resemble the cells in the human body. The model shows great promise for the future even though additional tests are needed. The sooner we know how good a chemical is, the sooner we can predict which chemicals will work and not. Which could lead to a drug development that is more cost-effective, time efficient and involves less animal suffering

Supervisor: Stina Oredsson, Atena Malakpour-Permlid
Bachelor thesis 15 hp in MOBK01
Department of biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Friberg, Nathalie
supervisor
organization
course
MOBK01 20211
year
type
M2 - Bachelor Degree
subject
language
English
id
9060098
date added to LUP
2021-06-30 16:24:00
date last changed
2021-06-30 16:24:00
@misc{9060098,
  author       = {{Friberg, Nathalie}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Comparison of 3D PCL scaffold model with traditional 2D model in the HTS system for anti-cancer drug development}},
  year         = {{2021}},
}