Regeneration, Repair and Healing of Tissues (Process Of Healing)

Regeneration, Repair and Healing of Tissues

 Regeneration

It means the restoration of original structure and function, lost during the inflammation.

Repair

It implies filling up of gap created by the inflammation with non- functional scar tissue.

Healing

It implies the disappearance of the process of  inflammation and its replacement by either regeneration or repair or both in varying proportions.

Regeneration and Repair

Regeneration is the renewal of a damaged tissue or a lost appendage that is identical to the original one. Regeneration requires a population of stem or precursor cells with the potential to differentiate and replicated. The regeneration of injured cells and tissues involves cell proliferation which is driven by growth factors and is critically dependent on the integrity of the extracellular matrix.

Several  cell types proliferate during tissue repair. These include the remnants of the injured tissue, vascular endothelial cells and fibroblasts. The proliferation of these cell types is driven by proteins called growth factors. The production of polypeptide growth factors and the ability of cells to divide in response to these factors are important determinants of the adequacy of  the repair process. Biochemical signals draw the stem cells to sites where growth factors have created an environment for regeneration.

Growth factors

They induce cell proliferation by binding to specific receptors and affecting the expression of genes whose products typically have several functions.

• They promote entry of cell into the cell cycle
• They relieve blocks on cell cycle progression thus promoting replication
• They prevent apoptosis
• Enhance the synthesis of cellular proteins in preparation for mitosis.
• Stimulate the function of growth control genes because mutations in them lead to unrestrained cell proliferation characteristic of cancer.

Below is the list of few common growth factors along with their sources and functions:

Growth Factors	Sources	Functions
Epidermal Growth Factors(EGF)	Activated by macrophages, salivary glands, keratinocytes and many other cells.	Mitogenic for keratinocytes and fibroblasts  Stimulates keratinocytes migration  Stimulates formation of granulation tissue
Keratinocyte growth factor (KGF)	Fibroblasts	Stimulates keratinocytes migration Proliferation and Differentiation
Hepatocyte growth factor (HGF)	Fibroblasts, stromal cells in the liver, endothelial cells.	Enhances proliferation of hepatocytes and other epithelial cells. Increases cell motility.
Vascular endothelial growth factor (VEGF)	Mesenchymal cells	Stimulates proliferation of endothelial cells  Increases vascular permeability.
Platelet derived growth factor (PDGF)	Platelets, macrophages, endothelial cells, smooth muscle cells, keratinocytes.	Chemotactic for neutrophils, macrophages, fibroblasts and smooth muscle cells.  Activates and stimulates proliferation of fibroblasts, endothelial and other cells. Stimulates ECM protein synthesis.

Role of Extracellular Matrix

Repair of tissue after injury depends on the synthesis of a fibrous extracellular matrix to replace lost or damaged tissue. Newly deposited extracellular matrix is then re-modeled over time to emulate normal tissue. The extracellular matrix directs repair by regulating the behavior of the wide variety of cell types that are mobilized to the damaged area in order to rebuild the tissue. Acute inflammation, re-epithelialization, and contraction all depend on cell-extracellular matrix interactions and contribute to minimize infection and promote rapid wound closure. Matricellular proteins are up-regulated during wound healing where they modulate interactions between cells and the extracellular matrix to exert control over events that are essential for efficient tissue repair.