Tissue Renewal, Regeneration and Repair

Tissue Renewal, Regeneration and Repair Introduction and objectives: to gain knowledge about: Types of tissue renewal Types of cells according to division power Stem cells: definition- characters- division Cell cycle: characters and functions Angiogenesis and granulation tiss...

Tissue Renewal, Regeneration and Repair Introduction and objectives: to gain knowledge about: Types of tissue renewal Types of cells according to division power Stem cells: definition- characters- division Cell cycle: characters and functions Angiogenesis and granulation tissue Types, steps and complications of wound healing Bone healing Nervous tissue repair Tissue Renewal, Regeneration and Repair The process by which the body forms new cells to replace structures damaged in pathological process. Two types of tissue renewal: Regeneration: Healing by same type of cells Repair: Healing by mixture of same cells and fibrosis  Conditions for regeneration - Tissue composed of labile or stable cells - Presence of good number of stem cells - Less amount of tissue damage - Intact connective tissue matrix - Ex: very superficial skin wound- bone fracture  Conditions for repair - Tissue composed of permanent cells - Small number of stem cells by tissue damage - Severe tissue damage - Destruction of connective tissue matrix - Chronic inflammation - Ex: Wound healing (1st & 2nd intention)  Labile cells Ex: Epidermis, GIT, Endometrium and blood cells Characters: short life span- continuous proliferation- large number of stem cells  Stable cells Ex: liver- fibroblast-osteoblast Characters: replicate until reaching the adult size then stop Most of their life in G0 of cell cycle Can be active and replicate again if stimulate (bone fracture)  Permanent cells Ex: nerve cells, cardiac muscle and skeletal muscle fibers Don’t replicate in post natal life Under tissue stress, they tend to increase in size (hypertrophy) of functional capacity (CNS cells) In damage condition they are replaced by fibrous tissue (glial tissue)  Stem cells Undifferentiated cells that can: - Turn into many types of differentiated cells - Self renewal: divide to make more stem cells They maintain their numbers and population through two types of divisions: - Symmetric division: one stem cell can replicate itself and create two stem cells. - Asymmetric division: one stem cell can divide into one similar stem cell and differentiated cell. Stem cell division Stem cell division A: stem cell B: progenitor cell C: differentiated cell 1: symmetric stem cell division 2: asymmetric stem cell division 3: progenitor division 4: terminal differentiation  Adult stem cells Adult (somatic) stem cells: they have been identified in many mature tissues as bone marrow, GIT, skin, liver, pancreas, and adipose tissue. Typically they have a more limited capacity to differentiate. Sources of stem cells: bone marrow, adipose tissue, blood and umbilical cord blood.  Cell cycle It is the ordered sequence of events that occurs in a cell in preparation for cell division. The cell cycle is a four stage process in which the cell 1- Increase in size (G1: growth) stage 2- Copies its DNA (S: DNA Synthesis) stage 3- Prepare to divide (G2: growth and preparation for mitosis) stage 4- Divides (M: mitosis) stage Cell cycle and regulation of cell replication Cyclin and cyclin dependent kinases (CDKs)  Characters of cell cycle Continuously dividing labile cells can enter G1 phase directly after completing mitosis (M) phase. Stable cells can re-enter the cycle from G0 to G1 when needed. Cell cycle has two check points (G1-S) and (G2-M) which act as surveillance for any DNA damage. The cell cycle progression is controlled by a family of proteins named cyclin and cyclin dependent kinases (CDKs). The main role of these complexes are controlling and signaling the cells that are ready to pass into the next phase during the cell cycle.  Characters of cell cycle Positive regulators of cell cycle like growth factors typically increase the activity of cyclins and Cdks Epidermal growth factor receptors (EGFR) are family of four different transmembrane proteins. Mutation and over expression of EGFR1 is associated with different malignancies. EGFR2 is also called HER-2 neu receptor. It’s over expression is associated with poor prognosis of breast cancer.  Characters of cell cycle Negative regulation like DNA damage typically decreases or blocks the activity of cyclins and Cdks. P53 is a tumor suppressor protein works to ensure that cells with DNA damage do not pass through cell division by triggering the production of Cdk inhibitor.  Objectives to gain knowledge about: Angiogenesis and its role in repair process Granulation tissue Types of wound healing Steps of wound healing Complications of wound healing Bone healing  Angiogenesis Definition: it is the formation of new blood vessels (neovascularization) Importance: - Formation of granulation tissue. - Vascularization of ischemic tissues. Granulation tissue is a new tissue that is formed of fibroblasts, collagen , newly formed blood vessels and inflammatory cells. It is used for replacement of damage tissues that can not regenerate. It ends in fibrosis and scar formation  Steps of angiogenesis 1- Vasodilatation of preexisting vessels by nitric oxide. 2- Increased permeability by vascular endothelial growth factor. 3- Breakdown of basement membrane by metalloproteinase. 4- Disruption of endothelial cells contact by plasmin. 5- Proliferation of endothelial cells. 6- Maturation of endothelial cells. 7- Recruitment of peri-endothelial cells as pericytes and vascular smooth muscle. Angiogenesis Granulation tissue Healing by first intention Healing by second intention (Primary union) (Secondary union) clean cut wounds as surgical incision septic wounds, ulcers and abscesses. minimal cell death and minimal marked cell death and marked basement membrane damage basement membrane damage The edges of the wound are closely A wide gap is present. The approximated by suture edges are not in contact There is no foreign body or infection. Foreign body or infection may be present. minimal fibrosis and good re- Dense fibrosis, greater epithelialization (minimal scar). angiogenesis and abundant collagen deposition (dense scar) No scar contracture Significant scar contracture Types of wound healing  Steps of wound healing Formation of blood clot Formation of granulation tissue Cell proliferation and collagen deposition Scar formation Wound contraction Connective tissue remodeling Complications of wound healing Infection Inadequate granulation tissue formation leads to ulceration Keloid formation: excessive formation of granulation tissue that produces a hypertrophic scar covered by thin epidermis. Keloid is due to overdone repair. Wound contracture: reduction in the size of the scar due to excessive contraction Keloid and wound contructure  Bone healing Bone healing is an example of regeneration Steps of bone healing - Formation of hematoma - Polymorphs, macrophages, fibroblasts and new blood vessels - Osteoprogenitor cells, osteoblasts and osteoclasts. - Osteoid tissue: collagen- fibroblasts- little amount of calcium - Osteoblasts secrete alkaline phosphatase leading to more calcification - The osteoid tissue acts as fixator and is arranged in three layers termed calli  Steps of bone healing A) External callus: to the outside under the periosteum. B) Internal callus: in medullary canal. C) Intermediate or permanent callus: found in between the two ends of fractured bones. - The osteoblasts of the intermediate callus will form the bony callus by progressive mineralization - The external and internal calli will be gradually removed by osteoclasts Steps of bone healing  Repair of nervous system 1- The central nervous system: The nerve cells are permanent cells. Injury to the central nervous system is not followed by extensive regeneration. It is limited by the inhibitory influences of the glial and extracellular environment. Steps of CNS repair: - Necrosis and liquefaction of injured area. - Microglia (Macrophages of CNS) removes debris. - Astrocytes (supporting cells) proliferate and replace the lost area (Gliosis or glial scar). 2- The peripheral nerves: The peripheral nervous system has an intrinsic ability for regeneration. Steps of peripheral nerve regeneration: - The axon distal to injury becomes irregular and myelin sheath breaks into droplets up to the level of the first node of Ranvier (Wallerian degeneration). - Macrophage and Schwann cells remove debris. - The Schwann cells (supporting cell) in both the proximal and the distal ends proliferate and unite together forming a tube in which new myelin is formed by oligodendroglia. - A new axon grows from the proximal segment (axonal sprouts) and elongates gradually until it reaches the required length.