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TISSUE RENEWAL, REPAIR & REGENERATION

PROLIFERATIVE ACTIVITY
Labile tissue
Adult stem cells
Proliferate throughout life
Surface epithelia, lining of GIT , uterus
Hematopietic tissue

Quiescent tissue / stable


Divide in response to a stimulus
Low level of replication
Parenchymal cells liver, kidney, pancreas
Smooth muscle cells

Nondividing / permanent tissue


Left the cell cycle
Neurons, skeletal muscle, cardiac muscle

STEM CELLS
Self renewal

Give rise to cells of different lineages


Obligatory asymmetric replication
Stochastic differentiation

Embryonic stem cells (ES)

Adult/ Somatic stem cells


NICHES- special microenvironment

Induced pleuripotent stem cells (iPS)

Bone marrow

Hematopoietic stem cells

Marrow stromal cells

Liver -Canal of Hering, Oval cells

Brain -Neural stem cells

Skin

Intestinal epithelium Paneth cells

Skeletal & cardiac muscle

Cornea Limbus cells

POTENCY OF CELLS
Totipotent stem cells
Differentiate into embryonic & extraembryonic cell types
Cells produced by the first few divisions of the fertilized egg

Pluripotent stem cells/ Embryonic stem cells


Differentiate into all tissues of the body

Multipotent stem cells


Closely related family of cells
Limited differentiation potential

Oligopotent stem cells


Restricted number of cells
Lymphoid or myeloid stem cells

Unipotent stem cell


Produce only one cell type
Property of self-renewal

TRANSDIFFERENTIATION

CELL CYCLE
G1- presynthetic

S - DNA synthesis

G2 - Premitotic

M - Mitotic

G0- Quiescent

Completion of previous phase

Activation of current phase

Restriction point

G1/S transition

DNA replication

Cyclins

Cyclin dependent kinases (CDK)

CDK inhibitors

CYCLINS, CDK & CDKI

CELL CYCLE & CHECK POINTS

EXTRACELLULAR MATRIX
Provides structural and biochemical support to the surrounding cells
Cell adhesion
Cell-cell communication
Growth & differentiation of cells
Scaffolding for tissue renewal
Storage & release of regulatory subtances
Interstitial matrix
Found between cells, in connective tissue
Basement membrane
Associated with cell surface

COLLAGEN
Most abundant protein

27 types of collagen

Structure - Three chains form a trimer to form a triple helix

Glycine is always in 3rd postion

4-hydroxyproline, hydroxylysine specialised aa

Hydroxyproline stabilises the triple helix

Fibrillar collagens

BM collagen form sheets

COLLAGEN
mRNA
Pre pro chains trimers
Hydroxylation of proline & lysine residues (VIT C)
Procollagen
Cleaved by proteases
Oxidation of lysine&hydroxylysine
Crosslinking