Regeneration
replacement of injured cells by cells of same type
Healing
tissue response to a wound (usually of skin), an inflammatory process in an internal organ, or to cell necrosis in an organ incapable of regeneration; involves two processes
two processes of healing
- regeneration
- scar formation (laying down of fibrous tissue
Cell proliferation is regulated by
- growth factors intrinsic to the microenvironment
- cell injury
- cell death
- mechanical stress (bone)
The most important regulator of cell growth and differentiation (healing) is:
prodding resting cells (G zero) to enter the cell cycle
Stable cells:
- quiescent cells
- usually G0 and low rate of division
- driven into G1 and rapid proliferation
- liver, kidney, pancreas, endothelium, fibroblasts
Labile cells
- always dividing
- replace dying cells
- epithelial cells of the skin, oral cavity, exocrine ducts, and GI tract; endometrium and bone marrow cells
Permanent cells
- non-dividing cells
- permanently removed from cell cycle
- irreversible injury leads only to SCAR
- nerve cells, myocardium, skeletal muscle
Stem cells
-prolonged self-renewal capacity and asymmetric replication (one cell retains its self-renewing capacity and the other enters a differentiation pathway)
Embryonic stem cells (ESC)
- used to study differentiation signals
- make possible production of knockout mice (inactivate or delete a specific gene in an ESC and inject the ESC into a blastocyst)
- have potential for repopulation of damaged organs
Adult stem cells (ASC)
more restricted differentiation capacity than ESC
- ASC exist in bone marrow and perhaps other tissues as well
- ASC are found in niches
Hematopoietic stem cells (HSC)
-give rise to all lineages of blood cells and possibly neurons and hepatocytes.
Where are stem cells found in the liver?
the canals of Hering
-these give rise to progenitor cells capable of differentiation into hepatocytes or biliary cells when liver injury is severe
satellite cells
- found in skeletal muscle, beneath the myocyte basal lamina
- they can differentiate into myocytes after injury
- sometimes they can also become osteogenic and adipogenic
Two major effects of Growth factors
- transcription of genes that were silent in resting cells
- regulate cell entry into and passage through the cell cycle
Four pathways of extracellular signaling
- Autocrine: the mediator acts on the cell that secretes it
- Paracrine
- Endocrine
- synaptic
Autocrine:
the mediator acts on the cell that secretes it
- cytokines on immune cells
- growth factors on epithelial cells
paracrine;
mediatory affects cells in the immediate vicinity
- inflammatory cells in infection sites
- wound healing process
endocrine signaling
regulatory substance (hormone) is released into the blood stream -ex insulin from islets of langerhans
angiogenesis
growth of new blood vessels
- derived from endothelial cell precursors (angioblasts) OR
- by budding from pre-existing vessels
- basement membrane degrades
- endothelial cells migrate, proliferate, and mature
In tissues capable of regeneration, ______ is required. If this is absent, healing by scar occurs
an intact connective tissue scaffold
proliferation requires summoning ____ cells into the cell cycle (primary) and _____ (secondary importance)
- resting or quiescent cells (G zero)
- shortening the cell cycle
PGF
polypeptide growth factors
proteoglycans and hyaluronan
growth factor reservoir
-binding water to ECM
