TISSUE RENEWAL AND REPAIR.pptx

7/30/2019 TISSUE RENEWAL AND REPAIR.pptx

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Tissue renewal and repairregeneration, healing, and fibrosis

C.Murtono

Dept.Pathological Anatomy

Medical Faculty UNIKA Atma Jaya


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Regeneration - healing

Regeneration: growth of cells to replace lost

structure. Tissue scaffold intact

Healing: Tissue response to wound, inflammatory

process, or to cell necrosis. Tissue scaffold

damaged.


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Control of tissue growth

Cell population determined by

- proliferation

myocytes, neuron is terminal (permanent)

hepatocytes if needed (stable tissue)

epithelial cell, always new (labile)

- differentiation-death by apoptosis

stimulated by physiologic, pathologic condition


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Stem cells

Characterized by prolonged self renewal

capacity and by asymmetric replication ( in every

cell division, one of the cells retains its self-

renewing capacity while the others enters adifferentiation pathway and converted to a mature

population)

1. first identified: embryonic stem cells(pluripotential cells)

2.adult stem cells


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Embryonic stem cells

Embryo contain pluripotent ES which can rise to

all tisue of human bodies . Can be isolated from

blastocyst (32 cell group)

ES cells be used to repopulate damaged organ

such as myocard after infarct.


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Adult stem cells

Many tisue in adult contain reservoir of stem cells

Not pluripotent, restricted differentiation

If located outside bone marrow: tissue stem cells


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Location of diverse tissue stem

cells

Epidermal stem cell: in the bulge of hair foll

Intestinal stem cells: at the base of colon crypt,

above Paneth cell

Liver stem cells (oval cells): in canal of Hering(connected the bile duct and parenchym cells)

Corneal stem cells: in limbus (between cornea andconjunctiva)


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Role of stem cells in tissue

homeostasis (I)

Liver: liver stem cells functions if hepatocyte

proliferation is blocked. After partial hepatectomy

or necrotizing injury, hepatocytes them cells

proliferate and stem cells are not activated.

In fulminant or chronic hepatitis and cirrhosis,

when hepatocytes proliferation is blocked, ovalcells proliferation is prominent


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Role of stem cells in tissue

homeostasis (II)

Skeletal and cardiac muscle: myocytes do not

generate. Regeneration of skelet muscle occur in

the form of proliferation of satellite cells, that

generate differentiated myocytes after injury.

Placed in different environment, satellite cells can

be osteogenic or adipogenic.


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Role of stem cells in tissue homeostasis (III)

Epithelial tissue: intermediate cells are highly

proliferative and terminally differentiated cells do

not divide and continously lost of the surface.

Brain: old dogma that NO neuron are generated

in adult mammals. Neural stem cells found in

olfactory bulb and in dentate gyrus ofhypocampus (protein nest in is the histologic

marker)


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Growth factors (I)

Polypeptide growth factors functions:

stimulates cell proliferation

cell locomotion

differentiation

angiogenesis


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Growth factors (II)EGF (epidermal growth factor) and TGF

alfa (transforming Growth Factor)

EGF: mitogenic for variety of epithelial cell, hepatocytes.Healing wound.

TGF-alfa: involved in proliferation of epithelial cell inembryo and adult and also malignant transformation ofnormal to malignant cells.

Fibroblast GF: angiogenesis, hematopoesis, skeletalmuscle development, wound repair


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Growth factors (III)

HGF(hepatocyte Growth factor): mitogenic effects inmost epithelial cells, incl. Hepatocytes and biliaryepithelium

VEGF (Vascular endothelial GF): potent inducer ofblood vessel formation/vasculogenesis and newblood vessel (angiogenesis)

Platelet Derived GF: migration and proliferation offibroblast, macrophages, and monocytes


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Growth factors (IV): TGF beta

Growth inhibitor for epithelial cell types and

leukocytes.

In mesenchymal cell: generally proliferation for

fibroblast and smooth muscle cell.

Potent fibrogenic

Strong anti inflammatory effect


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Signaling mechanisms in cell

growth

First: binding of signaling molecule (ligand) to cell

receptors

Based on the source of ligand and the location of

its receptor (same, adjacent, or distant cells)there are three modes of signaling: autocrine,

paracrine, and endocrine.


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Autocrine signaling

Cell respond to the signaling molecules that

themselves secrete

For examples: - liver regeneration

- proliferation of antigen-

stimulated

lymphocytes

Tumour frequently overproduces GFs and their

receptors


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Autocrine signaling


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Paracrine signaling

One cell type produce the ligand which then acts

on adjacent target cells that express the

appropriate receptors.

Common in wound healing. Factor produced by

one cell type (eg macrophage)has growth effects

on adjacent cell (*eg.fibroblast)


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Paracrine signaling


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Endocrine signaling

Hormone ia synthesized by cells of endocrine

organ and act on the target cells distant of their

sites of synthesis.

GF, eg HGF may also circulate and acts on distant

sites.


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Endocrine signaling


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Extra cellular matrix (ECM)

Macromolecule outside cells

1. fibrous structural protein

collagen, elastine

2. adhesive glycoprotein

3. proteoglycans, hyaluronic acid


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Cell adhesion molecule

(CAM) Several adhesion molecules play in part of

leucocytes migration, homing, and cell to cell

interaction.


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Repair by healing, scar formation and

fibrosis

Induction of inflammatory process

Proliferation and migration of parenchym and

connective tissue cell

Angiogenesis

Synthesis of ECM protein

Tissue remodelling

Wound contraction

Acquisition of of wound strength


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Factors that influences the repair

reaction

Tissue environment and extent of tissue damage

The intensity and duration of the stimulus

Condition that inhibit repair, as foreign body

Various diseases that inhibit repair


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Angiogenesis

In embryo: vasculogenesis, formed by endothelial

precursor cells (EPCs, angioblast)

In adult: angiogenesis (neovascularization):

-branching of adjacent blood vessel

-recruitment of angioblast from bone marrow

Critical for:-chronic inflammation

-tumour growth

-vascularization of ischaemic tissue


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Angiogenesis from Endothelial

Progenitor Cells.

Closely related with embryonal development.

2 systems: -hemangioblast, generate

hematopoetic stem cells

-angioblast proliferate, migrate to

peripher, and differentiate to endothelial cells

EPCs are stored in bone marrow and partisipate

in replacement of endothel, neovascularization of

ischemic organ.


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Angiogenesis from pre existing

vessel.

Vasodilatation and increased permeability ofvessel, degradation of ECM, migration ofendothel.

Vasodilatation in response to nitric oxide Degradation of BM by MMP

Migration of endothel by angiogenic stimulus

Proliferation and maturation of endothel Recruitment of pericytes and smooth muscle

cells


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Which GFs involved

VEGF, stimulates the mobilization of ECP from bonemarrow. Proliferation and differentiation in the site ofangiogenesis

PDGF, TGF-beta:stabilize the new vessel viaformation of ECM

cytokines

Hypoxia.


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Scar formation (I)

Fibroblast emigration and proliferation, which is

triggered by GFs TGF-beta, PDGF, FGF, EGF,

cytokines IL-1 and TNF.The source of this GFs is

inflammatory cells.

Incresed synthesis of collagen, decreased of

ECM by MMP.


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Cutaneous wound healing

3 phases: - inflamation

-granulation tissue

-wound contraction

2 types: healing by first intention, in uninfected

surgical wound

healing by second intention


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Process of wound healing


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TISSUE RENEWAL AND REPAIR.pptx