4-Regeneration and Repair

Question 0

Define healing

Answer 0

Process of regeneration and repair

Attempts to restore tissue integrity, structure and function

Question 1

What are the three possible outcomes of injury?

Answer 1

Overwhelmed and dies
Copes well: acute inflammation process and complete recover by regeneration/repair
Copes poorly: chronic inflammation process

Question 2

Define regeneration

Answer 2

Restitution of lost/damaged tissues

Question 3

Define repair

Answer 3

Variable restoration of damaged tissues by regeneration and scarring (connective tissue)

Question 4

What are the elements of regeneration and repair?

Answer 4

Cellular factors
Chemical mediators (growth factors)
Stromal factors
Additional factors

Question 5

What are the two types of cellular factors?

Answer 5

Tissue specific and non-tissue specific

Question 6

What are the two tissue tissue specific factors that govern regeneration in tissue?

Answer 6

Inherent nature of the cells

Relationship with the scaffold and blood supply

Question 7

How are tissue specific cells categorised? What are these categories?

Answer 7

Categorised by feplicative/proliferative potential

Labile
Stable
Permanent

Question 8

Describe labile cells

Answer 8

Rapid cell turnover

Present within one of the active phases of the cell cycle

Question 9

Give an example of a labile cell.

Answer 9

Epithelial cell

Haematopoietic cell

Question 10

Describe stable cells

Answer 10

Slow cell turnover

Present in the resting (G0) phase of the cell cycle - can be recruited/activated

Question 11

Give an example of a stable cell.

Answer 11

Mesenchymal cell (fibroblast, connective tissue, osteoblast, etc)
Parenchymal cell (hepatocytes)

Question 12

Describe permanent cells

Answer 12

No cell replacement/non-replicative

Left the cell cycle and cannot be recruited back

Question 13

Give an example of permanent cells

Answer 13

Cardiac myocytes

Neurons (skeletal muscle)

Question 14

What type of cells can proliferate in the cell cycle to restore lost tissue?

Answer 14

Labile and stable cells

Question 15

What are stem cells?

Answer 15

Cells that are capable of prolonged self renewal and asymmetric replication

Question 16

What does asymmetric replication mean?

Answer 16

After cell division one cell retains self renewing ability and the other will differentiate into a mature cell with no/limited ability to self renew

Question 17

What are the two categories for stem cells?

Answer 17

Embryonic and adult stem cells

Question 18

Describe embryonic stem cells

Answer 18

Formed at the 32 cell stage
Pluripotential
Asymmetric replication

Question 19

What are the disadvantages of adult stem cells in comparison to embryonic stem cells?

Answer 19

No asymmetric replication and are not pluripotent

Question 20

Where can adult stem cells be extracted from?

Answer 20

Bone marrow

Tissue (organ)

Question 21

What can adult stem cells from bone marrow differentiate into?

Answer 21

Haematopoietic stem cell -> blood cells (broad differentiation potential)

Question 22

What can adult stem cells from organ tissue differentiate into?

Answer 22

Multiplying adult progenitor cells
Can regenerate into the types of cells within that organ only (eg. Cells in liver cannot regenerate to form cells in skeletal muscle)

Question 23

What are the functions of macrophages?

Answer 23

Initiation and amplification of acute inflammation
Progression of chronic inflammation
Transition between inflammation and wound healing
Phagocytic removal of dead cells and matrix
Source of growth factors

Question 24

What are some of the growth factors produced by macrophages?

Answer 24

Platelet derived growth factor (PDGF) Fibroblast growth factor (FGF) Transforming growth factor (TGF) a & b Vascular endothelial growth factor (VEGF)

Question 25

What are the tissue non-specific cellular factors of regeneration and repair?

Answer 25

Macrophages Fibroblasts Endothelial cells

Question 26

What are the main functions of fibroblasts?

Answer 26

Provide structural integrity and tensile strength in wounds | Source of growth factors

Question 27

How do fibroblasts provide structural integrity and tensile strength to wounds?

Answer 27

Predominant cell type in connective tissue Stable cells - maintain capacity for rapid growth Proliferate locally and synthesise extracellular matrix components (collagen, fibronectin) Can become contractile (myofibroblasts)

Question 28

What growth factors are produced by fibroblasts?

Answer 28

Keratinocyte growth factor | Interleukin growth factor-1

Question 29

What are the functions of endothelial cells in relation to healing?

Answer 29

Responds to growth factors such as VEGF Source of growth factors - PDGF Restoration of blood supply to damaged tissues

Question 30

What is the main function of chemical mediators (growth factors) in the healing process?

Answer 30

Triggers for cell proliferation Stimulating cellular movement, contractility, differentiation, angiogenesis, critical processes in repair and regeneration

Question 31

List the growth factors that are polypeptides.

Answer 31

``` EGF, TGF-a (tyrosine kinase receptor) and HGF VEGF PDGF TGF-ß Cytokines ```

Question 32

Which growth factors are involved in epithelial cell proliferation?

Answer 32

EGF, TGF-a (tyrosine kinase receptor) and HGF

Question 33

Which growth factors are involved in vascular proliferation?

Answer 33

VEGF

Question 34

Which growth factors are involved in migration and proliferation of mesenchymal cells?

Answer 34

PDGF

Question 35

Which growth factors are pleiotropic-growth inhibitors for epithelial cells and leukocytes?

Answer 35

TGF-ß

Question 36

What is receptor mediated signal transduction?

Answer 36

Binding of growth factors to specific receptors on cells which stimulate the transcription of genes important in regulating entry and progression of cell cycle

Question 37

What are the three categories of receptor mediated signal transduction?

Answer 37

Autocrine Paracrine Endocrine

Question 38

What are autocrines? Give and example

Answer 38

GF produced locally and has an affect on same cell type/itself Liver regeneration

Question 39

What are paracrines? Give an example

Answer 39

GF produced locally to adjacent cell type (often different) Inflammatory and Stromal cells

Question 40

What are endocrines?

Answer 40

GF produced by cells at a distance from target cells and are transported via blood

Question 41

What is the role of the connective tissue stroma?

Answer 41

Functions as a scaffold for tissue The interaction between tissue cells and ECM determines if cells can adhere, migrate and proliferate

Question 42

What are some of the cells involved in the connective tissue stroma?

Answer 42

Fibroblast, fibrocytes, chondrocytes, osteocytes, Schwann cells, astrocytes

Question 43

The extracellular matrix (ECM) can be organised into what two components?

Answer 43

``` Interstitial matrix (IM) Basement membrane (BM) ```

Question 44

What are some of the components of the ECM?

Answer 44

Collagen and elastins Adhesive glycoproteins Proteoglycans and hyaluronic acid Water, minerals, growth factors

Question 45

What is the interstitial matrix?

Answer 45

Component of the ECM | Between epithelial, endothelial and smooth muscle cells

Question 46

What is the interstitial matrix comprised of?

Answer 46

Collagen (fibrillar and non-fibrillar), elastin, fibronectin, proteoglycans, hyaluronate

Question 47

What is the basement membrane produced by?

Answer 47

Epithelial and mesenchymal cells

Question 48

What does the basement membrane consist of?

Answer 48

Nonfibrillar collagen (IV), laminin, heparin SO4, proteoglycans, glycoproteins

Question 49

What is the key function of the ECM in relegation to the process of tissue healing and repair?

Answer 49

Osmotic drag for water Reservoir for minerals and growth factors Influence cell growth, movement (chemotaxis) and differentiation (by stromal factors)

Question 50

What are the cell surface adhesion molecules?

Answer 50

Adhesion glycoproteins, integrins, immunoglobulin superfamily, selectins, cadherins, CD44

Question 51

What are the matrix adhesion molecules?

Answer 51

Fibronectin, osteonectin, tenascin, laminin, vitronectin, fibrinogen, vWF, collagen

Question 52

What are the main function of cell adhesion molecules?

Answer 52

Provide interaction between cells (cadherins and immunoglobulin) Mediate adhesiveness between cells and ECM (integrins) Provide a mechanism for transmission of mechanical force/cell motility (cadherins and integrins)

Question 53

Describe the process of the signalling mechanisms in cell growth.

Answer 53

``` Signalling molecule (growth factor) binds to receptor Activates transducer Intracellular 2nd messenger Effector kinase Activates enzyme/transcriptor factor Modified gene transcription ```