Lecture 12: Healing and Repair 1

Question 1

Regeneration is?

Repair is?

Answer 1

Restitution by cells identical to those lost

Repair: Variabel amounts of regeneration, and tissue replacement by connective tissue scar

Question 2

What determines whether a tissue will regenerate or repair?

Answer 2

1- Cellular factors
2- Chemical mediators
3- Stromal Factors: ECM
4- Additional factors

Question 3

Classification of cells by proliferative potential

3 categories what are they?

Answer 3

Labile cells: most epithelial cells & haematopoietic cells.

Stable cells: mesenchymal cells, parenchymal cells. Cells are in G0 but can be stimulated to return to G1.

Permanent cells: cardiac myocytes, neurons (skeletal muscle). Cells have left the cell cycle.

Question 4

what are the 2 classes of Stem cells?

Answer 4

Embryonic stem cells: 32 cell stage; Pluripotential; asymmetric replication

Adult stem cells:
bone marrow-haematopoietic (HSC), progenitor & stromal); broad differentiation potential;
tissue stem cells: located in niches within most organ systems; Multipotent adult progenitor cells (MAPCS)

Question 5

organ regeneration or repair. What are the cells that are capable of this?

Answer 5

Labile tissues: replication of labile cells, niche stem cells
Stable cells: return of stable cells to cell cycle, replication of niche stem cells
Permanent cells: Limited/ no replication of permanent cells or niche stem cells.

Question 6

What are the essential Cellular elements of healing?

Answer 6

Macrophages
Pivotal role- initiation and amplification of acute inflammation
AND
progression of chronic inflammation and the transition between inflammation and wound healing.
- Essential role in phagocytic removal of dead cells and matrix.
- growth factors necessary to the wound healing process eg PDGF, FGF, TGF a & b, VEGF etc.

Question 7

Tell me about Fibroblasts and their role in healing

Answer 7

Fibroblasts
main cell type in connective tissue;
stable cells
essential to wound repair:
ECM components: eg collagen, fibronectin structural integrity and tensile strength in wounds.
Growth factors eg keratinocyte growth factor, IGF-1.
heterogeneous: some become contractile (myofibroblasts) -critical in wound contraction.

Question 8

What is the role of endothelial cells in healing

Answer 8

Endothelial cells
respond early to growth factors such as VEGF (from macrophages, epithelium) at the site of tissue injury.
a source of important growth factors (PDGF).
early proliferation restoration of blood supply to the damaged tissue,
Newly formed blood vessels = very leaky, releasing fluid nutrients and also proteins (eg Ab, complement proteins) and cells important in the immune response.

Question 9

Whats the general gist of healing. Whats involved?

Answer 9

Healing occurs following tissue injury-initiated within minutes/ hours of tissue injury.

Fibrin:
=“tissue glue” to hold the tissue together
=scaffold for the inflammatory response,
FDP’s and oedema activate tissue fibroblasts  + repair process.

Healing =
attempts to restore tissue integrity,
tissue structure
and function.

Question 10

What are the triggers for cell proliferation

Answer 10

Growth factors:
Key initiators of cellular proliferation, also locomotion, contractility, differentiation & angiogenesis
Polypeptides:
EGF, TGF-a (tyrosine kinase receptor)& HGF: epithelial cell proliferation;
VEGF: vascular proliferation
PDGF: migration and proliferation of mesenchymal cells
TGF-b:pleiotropic- growth inhibitor for epithelial cells and leukocytes; stimulates fibroplasia
Cytokines: IL, IFN, TNF

Question 11

What are the signalling mechanisms in cell growth?

Answer 11

Receptor mediated signal transduction:
Autocrine: locally to themselves eg liver regeneration
Paracrine: locally to adjacent (often different) cell type eg inflammatory cells and stromal cells
Endocrine: via blood to distant cells.

Question 12

Whats the role of growth factors in liver regeneration?

Answer 12

slide 17

Question 13

Whats the role of connective tissue Stroma

Answer 13

Functions as a scaffold for tissue.
Functions as a scaffold for tissue.
Cells: fibroblasts, fibrocytes, chondrocytes, osteocytes, Schwann cells, astrocytes.
Extracellular matrix: 
Collagens & Elastins
Adhesive glycoproteins
Proteoglycans & hyaluronic acid	
Water, minerals & growth factors

Question 14

The ECM plays a role in what?
The ECM is organised into?
The interstitial Matrix?
The basement membrane?

Answer 14

The ECM plays a pivotal role in tissue regeneration and repair.
It is the interaction between tissue cells and the ECM that determines whether cells can adhere, migrate and proliferate.
Synthesis & degradation of the ECM accompanies morphogenesis, wound healing, chronic fibrosis, neoplastic invasion and metastasis

The ECM is organised into:
The interstitial matrix
The basement membrane

Question 15

Discuss the cell Matrix Reactions?

Answer 15

Cells migrate across surfaces made of Extracellular Matrix.
Chemotaxis = directed migration along a concentration gradient.
Cell differentiation / phenotypic expression is largely determined by the local stromal environment.
Cell surface molecules interact with matrix glycoproteins.
19,20,21

Question 16

Adhesion Proteins

Answer 16

22
Cell surface adhesion molecules:
Adhesion glycoproteins, Integrins, Immunoglobulin superfamily, Selectins, Cadherin, CD44.

Matrix adhesion molecules:
Fibronectin, Osteonectin, Tenascin, Laminin, Vitronectin, Fibrinogen, vWF, Collagen

It is the interaction between cell surface adhesion molecules and the matrix adhesion molecules that determines cell growth, motility, differentiation and protein synthesis

Question 17

Healing by repair is the restoration of damaged tissue by regenerating and scaring.
Repair involves 7 basic steps:

Answer 17

1. Inflammation in response to tissue injury, with removal of damaged and dead tissue
2. Proliferation and migration of parenchymal and CT cells
3. Angiogenesis & granulation tissue formation
4. Synthesis of ECM proteins and collagen
5. Tissue remodelling
6. Wound contraction
7. Acquisition of wound strength

Question 18

What are the factors effecting tissue repair?

Answer 18

• continued tissue damage by the original agent or a secondary agent - especially bacterial infections and foreign bodies (local);
• poor nutrition - particularly protein, Vitamin A, Vitamin C, Zn (systemic);
• poor blood supply in the area - this varies from organ to organ (systemic or local);
• metabolic disturbances e.g. diabetes, hyperadrenocorticism (systemic);
• low temperatures (local or systemic);
• low immune status (systemic).
• Mechanical factors (local)