tissue Repair

Tissue repair = restoration of tissue architecture and function after an injury
Occurs in two ways:
Regeneration of injured tissue
Replacement by connective tissue (scarring)
Usually, tissue repair involves both processes
Involves cell proliferation, and interaction between cells and extracellular matrix



Important points :
Cellular proliferation
Growth factors
The extracellular matrix

Cells that proliferate during tissue repair include
Injured tissue remnants.
Vascular endothelial cells.
Fibroblasts.
The Cell Cycle
Physiologic cell proliferation – repair
Pathologic proliferation – cancer
Key processes to the cell cycle are DNA replication and mitosis
Steps:
Presynthetic growth phase 1 (G1)
DNA synthesis phase (S)
Premitotic growth phase 2 (G2)
Mitotic phase (M)
Non-dividing cells are either in the cell cycle arrest in G1 or they exit the cycle to enter a phase called G0




Proliferation Capacity
Ability of tissues to repair themselves is influenced by their intrinsic proliferative capacity

Three types of tissues
Continuously dividing tissues (labile tissues)
Stable tissues
Permanent tissues

Continuously dividing tissues (labile tissues)

Lost and replaced by maturation from stem cells and by proliferation of mature cells.

These cells have a short life span
Bone marrow, skin, oral mucosa, GI tract, ducts draining exocrine glands


Stable tissues

Quiescent cells (G0 stage) – have minimal replicative activity - can proliferate in response to injury and loss of tissue mass.

Constitute the parenchyma of solid tissues – long life span
– kidney, liver, pancreas, endothelial cells, fibroblasts, smooth muscle cells

Permanent tissues

Terminally differentiated and nonproliferative in postnatal life.

Long life span - neurons, cardiac and skeletal muscle.
Stem Cells
Source of mature cells
Homeostatic equilibrium between replication and differentiation of stem cells and the death of the mature , fully differentiated cells
Examples are skin and GI tract
Two important characteristic properties of stem cells:
Self-renewal capacity
Asymmetric replication
Some differentiate to a specific cell type
Some remain undifferentiated
These maintain their self-renewal capacity


Stem Cells
Pluripotent stem cells
Capacity to generate multiple cell lineages
When isolated from embryos – embryonic stem cells
Tissue stem cells (adult stem cells)
Can generate multiple lineages
Bone marrow – fat, cartilage, bone, endothelium, muscle





Growth Factors
Cell proliferation can be triggered by:

Growth factors, hormones, cytokines.

Growth factors produced by leukocytes, parenchymal cells, and connective tissue.


Growth factors effects:
Expanding cell population
Stimulating cell division (mitosis)
Increase cell size (growth)
Protection from apoptotic death (survival)

Stimulate migration, differentiation, angiogenesis, contractility, and fibrogenesis
Involved in growth control – can stimulate or inhibit
May act on multiple cell types



Extracellular Matrix (ECM)
Tissue repair depends on interactions between cells and ECM.

Regulates proliferation, movement, and differentiation of cells within it.



Two forms of extracellular matrix:
Interstitial matrix
Located in spaces between cells in connective tissue, and between epithelium and vascular/smooth muscle structures
Basement membrane
Interstitial matrix of connective tissue that is highly organized around epithelial, endothelial and smooth muscle cells
Found between epithelium and mesenchymal cells



Role of Extracellular Matrix
Mechanical support : Anchorage, migration
Control of growth
Signals through cellular receptors - integrins
Maintenance of cell differentiation
Proteins affect degree of differentiation
Scaffolding for tissue renewal
Basement membrane needed for renewal of structure (stroma)
Labile and stable cells depend on ECM to reestablish normal structure
Storage of growth factors
Allows for rapid response to injury and healing


Angiogenesis
Two processes
Vasculogenesis – new vascular network forms during embryonic development
Angiogenesis (neovascularization) – preexisting vessels send out capillary sprouts
Needed for healing at injury site
Increase to treat ischemia - cardiac
Tumor – allows for further growth - inhibit to control cancer


Scar Formation
Builds on the granulation tissue framework
There are 2 steps
Migration and proliferation of fibroblasts
Deposition of ECM by these cells
Granulation tissue eventually becomes a pale, largely avascular scar
Composed of collagen, fibroblasts, elastic tissue
Remodeling
Depends on the balance between ECM synthesis and degradation