Mechanobiology, bioreactors & mechanical forces (lecure 4)

Question 1

How do cells sense forces?

Answer 1

Mechano-sensitivity is primarily thriough the integrin-mediated Focal adhesions (FA)-to the actin cytoskeleton

Question 2

What are the types of tissue?

Answer 2

Epithelial
Nervous
Muscle
Connective

Question 3

Wjat is the ECM and how does it affect cells?

Answer 3

Complex network if macromolecules synthesised, secreted, arranged and modified by cells

ECM affects cells in return and influences cell fate processes like proliferation, differentiation, migration, and cell death

Question 4

What is the composition of ECM?

Answer 4

Proteins & Glycoaminoglycans (GAGs). Both sulphated and non-sulphated

Question 5

What are MMPs?

Answer 5

Metalloproteinases

Play an important role in tissue remodeling associated with various physiological and pathological processes such as:
- morphogenesis
- angiogenesis(formation of blood vessels)
- tissue repair
- metastasis

Question 6

What are the hypotheses for causes of disc degeneration?

Answer 6

Mechanical hypothesis: mechanical overload, causes cell death and mechanical failure

Biological hypothesis: Initial failure of cells, then mechanical failure due to lack of tissue homeostasis

Question 7

Whya re bioractors used for intervertebral disc research?

Answer 7

1. more complex than simple monolayer culture
2. much less expensive than in vivo animal models
3. highly appealing to test basic research questions
4. appealing for translational research

Question 8

What is a method to treat disk pain?

Answer 8

Injectable disc cell therapy

Question 9

What are the advantages of bioreactors?

Answer 9

• Organ culture models of the IVD/cartilage/bone can mimic the human in vivo situation under most physiological conditions and can serve as feasibility instruments prior to animal testing.
• Regenerative Strategies can be tested on a “mind-map” with realistic conditions.
• Bioreactors comply with the increased ethical hurdles with animal experimentation and comply with the 3R rules.

Question 10

What are the limitations of bioreactors?

Answer 10

• The culture conditions may be limited to certain short-term (2–7 days) to mid-term experiments (14 days–1 month) due to ex vivo culture conditions/3D nutrient limitations.
• The lack of an immune response does not allow testing the host response.
• Complex tissues cannot be cultured due to restrictions in the number of cells that can be cultured.