(Lecture 3) (p3_ECM_6.pdf) iPSC and ECM

What is the extracellular matrix (ECM)?

The ECM is the collection of secreted products of cells in tissues and organs that provides:

• mechanical support

• signal transduction for cell-cell and cell-matrix interactions

What are the main types of ECM molecules?

Structural and Functional

What are the main types of ECM?

• Basement membrane (basal lamina)

• Elastic fibre ECM

• Stromal/interstitial matrix

Why is collagen important in the ECM?

tissue stability, structural integrity, support for differentiation, polarity, and movement

Where is collagen commonly found?

cartilage, ligaments, tendon

What does Type I collagen do?

provides uniaxial and multiaxial mechanical strength

What does Type III collagen do?

Type III collagen is found in flexible, compliant tissues, such as the submucosal layers and urinary bladder.

What does Type IV collagen do?

Type IV collagen is found in the basement membrane of vascular structures and has ligand affinity for endothelial cells.

What is fibronectin?

helps connect cells to collagen fibres

What are the main functions of fibronectin?

promotes cell adhesion, helps cells move through the ECM, links cells to collagen or proteoglycans

What sequence in fibronectin promotes cell adhesion?

RGD sequence (Arg-Gly-Asp)

Why is fibronectin useful in tissue engineering?

It can be used as a coating for synthetic scaffold materials to improve cell attachment.

What is laminin?

adhesion molecule found in basal membranes

What does laminin do?

binds other ECM components

What is elastin?

major protein of elastic tissues

What is tropoelastin?

soluble precursor of elastin

What are proteoglycans?

Heavily glycosylated molecules made of a core protein and one or more attached GAG chains

What are glycosaminoglycans (GAGs)?

long linear carbohydrate polymers

Why are GAGs negatively charged?

Because they contain sulfate and uronic acid groups.

What are the two main subunits of GAGs?

Uronic acid, Aminosugar

How are GAGs attached to proteins?

They are linked to the protein core by a specific trisaccharide linker

What are the main types of GAGs?

• Hyaluronic acid

• Chondroitin sulfate

• Dermatan sulfate

• Heparan sulfate

• Keratan sulfate

What is special about hyaluronic acid?

non-sulfated, binds lots of water, helps tissues resist compression

Where is hyaluronic acid especially abundant?

load-bearing joints and interstitial gel

What are the main functions of proteoglycans?

organize water, resist compression, provide viscosity/lubrication

What are the main structural glycoproteins in ECM?

Fibronectin, Laminin

Why are growth factors important in ECM?

regulates cell growth, migration and proliferation

Name some growth factors found in ECM.

Examples:

• VEGF

• FGF

• SDF-1

• EGF

• TGF-β

• PDGF

• BMP

What does VEGF do?

stimulates blood vessel formation.

What does BMP do?

induces bone formation

What is decellularised ECM?

It is ECM from which cells have been removed, leaving behind the bioactive scaffold.

Why is decellularised ECM useful?

reduces immune rejection, keeps cell-binding sites, retains some growth factors

What are the criteria for efficient decellularisation?

No visible nuclei

What is whole-organ decellularisation?

removal of cells from an entire organ

What is the main tissue engineering lesson from ECM?

Successful scaffolds should mimic ECM:

• composition

• hierarchy

• adhesive ligands

• hydration/transport properties

• dynamic behaviour