College 1
- The human fetus has a high regenerative potential. Blood and bone marrow are also
highly regenerative.
- Hydra is a small organism that can regenerate the head and tail. The Wnt-beta-
catenin pathway is very involved in this. It has continuous mitosis and migration
towards extremities.
- Neonatal mice regenerate their toe tips.
- The regenerative capacity in humans is very low, due to the role of stem cells, which
contribute to homeostasis and repair. Organs
have a low regeneration turnover. These
tissues have stem cells as well, but only a few.
They are called terminal tissues. Stem cells of
tissues with a high regenerative capacity can be
used to create these terminal tissues.
- Regenerative medicine aims at cure and
complete functional recovery and allows for
growth and adaptation. There are three fields of
research:
1. Tissue engineering (cells are seeded in a scaffold, which
thereafter can be implemented)
2. Stem cell therapy
3. Molecular induction of regeneration.
- You can make tissues in the lab, but the body rejects them,
even when the patient’s own cells are used. The immune
system always reacts to new tissues and therefore this system
plays a huge role in regeneration.
- Skin and cartilage have a low blood and nutrients supply. They
are also simple structures, which why they can be replaced very well.
- Adherent (circulating) cells: cells that require attachment to a surface or ECM through
specialized structures call focal adhesions for growth, survival and proliferation.
Examples: fibroblasts, endothelial cells, epithelial cells, smooth muscle cells. When
blood cells are used to create tissues, they need to be adapted to function as
adherent cells.
- Non-adherent (circulating) cells: can grow freely in solution. Examples: immune cells
such as lymphocytes, macrophages and red blood cells.
- Visualizing living cells is done by vital imaging -> observing living cells.
- Cells can adhere to their environment. This can result in deformations. Cells are
visco-elastic. A tissue cell is stiffer compared to non-adherent cells. If a cell is stuck to
a flat surface, the secretion surface is bigger.
- Cell motion (/migration): process by which cells move from one location to another.
, 1. Extension: the cell extends part of its membrane
forward in the direction of movement. This is done by
polymerization of actin filaments in the cytoskeleton.
Two types of extension: 1. Lamellipodia: broad, flat
membrane extensions at the leading edge of the cell.
2. Thin, spike-like extension that sense the
environment and guide the direction of migration.
2. Adhesion: The cell establishes focal adhesions. This
happens through integrins.
3. Retraction: older focal adhesions are disassembled
and the trailing edge retracts. This allows the cell to
free its tail and move forward.
- Cell membrane: viscous, double layer of phospholipids
including proteins, carbohydrates and cholesterol, very
flexible, allows active and passive transport. It is a
division between inside and outside.
- Cytoplasm: Gel-like, visco-elastic material containing
cytosol, organelles, vesicles, and cytoskeleton.
- Cytoskeleton: support the structure of the cell and has 3
fibrillar protein types:
1. Actin
2. Intermediate filaments
3. Microtubules
- The cytoskeleton movement is important for cell division, migration
and transport. It requires dynamic filaments and molecular
motors. The organization and mechanical properties of
actin/microfilaments are important for cell function.
Filaments form compact fiber bundles or loose networks.
They play a role in cell contraction, movement, transport
and the cell phenotype. They are linked to the ECM through
integrins (focal adhesion points).
- F-actin forms stress fibers in adherent cells. The stress
fibers can pull at the environment using the focal adhesion
points. The extracellular surface (hydrogel) dictates the
stiffness of these stress fibers.
- The formation of stress fibers:
1. Stress fibers consist of bundles of actin filaments, aligned in parallel. They are
connected by crosslinking proteins. Myosin II motors is a motor protein that can
“walk” along actin filaments. They pull together the actin filaments, creating
contractile forces in the cell.
2. Stress fibers can contract and create tension.
3. The formation of stress fibers is controlled by a
signaling pathway that involves the small GTPase
protein called RhoA, which regulates actin
cytoskeleton, when activated -> promotes contractile
function.
4. Stress fibers are essential for cell adhesion to the
substrate, contractile tension and changes in cell
shape.
,- Intermediate filaments are rigid stable elements, they provide tensile strength to the
cell. It concerns anchor cells or cells with matrix.
- Microtubules, thick filaments:
Hollow Fibers of tubulin microfilaments
Connected to centrosome, near nucleus
Movement and transport
Determine cell shape and distribution of organelles
- Nuclear lamina can be missing, which causes rapid ageing and weakness of cells.
The nucleus is linked to the environment of the cell via these laminas. A stiff external
environment causes stress fibers to pull, which leads to pulling apart of the nucleus
and apoptosis.
- Cell-cell and cell-matrix connections provide a continuous network between ‘intra’
and ‘extra’ cellular environment. The cellular micro-environment = ‘niche’.
- The matrix can control cell fate:
• cell-matrix interactions
• matrix stiffness
• matrix molecules
• Soluble signals
- The cell shape and function in tissue morphogenesis (develop shape) is determined
by:
Substrate flexibility -> stiff substrate = more contractile -> soft substrate = less
contractile.
Ligand type -> influences how the cell moves and what it becomes
Ligand density -> high density = strong attachments, more tension -> low density =
weak attachments, less spreading/tension.
- Cells determine matrix synthesis and degradation by cell-matrix reciprocity: the cells
control their matrix and the matrix controls the cells. The cell produces molecules and
can break down its own environment. Cells are shielded from force by their ECM.
- Cell maintain and repair the tissue, they produce their
own matrix (ECM) and they control it. The fibrillar
components are: collagen, elastin and GAGs. ECM is
relevant for structure, function, adaptation and
remodelling. The ECM also exists of fibronectin,
laminins and proteoglycanen.
- Triggers for growth or proliferation:
◦ Based on ‘supply and demand’
◦ To ‘reach homeostasis’
◦ Physical limitations: Ratio cell size / nuclear size
◦ Stimuli originate in cytoplasm (intrinsic)
◦ Stimuli from extracellular environment (‘molecular signaling’ and mechanical cues)
, - Interstitial growth = produced by division and activity of mature
cells (in the whole tissue).
- Appositional growth = Growth on a local location in the tissue.
- Growth: cell division. Not all cells divide and grow at the same
time (though the ‘first cells’ will do). Also not all cells and tissues
grow at the same rate, but growth is controlled.
- Cells stop growing when they touch each other (contact
inhibition). This results in the formation of a monolayer. However, when
there are cancer cells, they grow on top of the layer. It leads to a focal
point (focus).
- Tissue growth and homeostasis occurs either via stem cell division or
via ’normal’ cell division.
- Stem cells can renew itself indefinitely (‘self-renewal’) and upon division
can turn into another cell type. But has a low turnover, because they
divide infrequently under normal conditions. Adult stem cells have a low
turnover, but embryonic stem cells have a high turnover, as they are
involved in rapid growth.
• Totipotent (stem)cells: can differentiate into all cell types: the egg and
sperm cells and the first cell divisions of the fertilized ovum.
• Pluripotent (stem) cells: can differentiate into most cell types.
• Multipotent (stem)cells [purple]: can differentiate into many/several cell
types, usually of the same organ
• Differentiated, unipotent cells [blue]
• Terminally differentiated cells [yellow]
- Stages of development:
1. Embryonic growth and differentiation
2. Postnatal growth, more increase in mass compared to differentiation.
3. Maturation; equilibrium between growth and
differentiation, synthesis and degradation;
maintenance of tissue function -> homeostasis.
4. More degradation; degeneration of function.
- Growth:
• By proliferation and activity of differentiated cells.
• By proliferation of stem cells that maintain the tissue.
- Proliferation is the increasing amount of cell, while differentiation is about gaining a
special function.
- Homeostasis is the balance between synthesis and degradation.
Ongoing proliferation of cells or tissue specific stem cell:
maintenance. In case of damage: tissue repair.
- Senescence: cell permanently stops with differentiating, but does
not die.
- The human fetus has a high regenerative potential. Blood and bone marrow are also
highly regenerative.
- Hydra is a small organism that can regenerate the head and tail. The Wnt-beta-
catenin pathway is very involved in this. It has continuous mitosis and migration
towards extremities.
- Neonatal mice regenerate their toe tips.
- The regenerative capacity in humans is very low, due to the role of stem cells, which
contribute to homeostasis and repair. Organs
have a low regeneration turnover. These
tissues have stem cells as well, but only a few.
They are called terminal tissues. Stem cells of
tissues with a high regenerative capacity can be
used to create these terminal tissues.
- Regenerative medicine aims at cure and
complete functional recovery and allows for
growth and adaptation. There are three fields of
research:
1. Tissue engineering (cells are seeded in a scaffold, which
thereafter can be implemented)
2. Stem cell therapy
3. Molecular induction of regeneration.
- You can make tissues in the lab, but the body rejects them,
even when the patient’s own cells are used. The immune
system always reacts to new tissues and therefore this system
plays a huge role in regeneration.
- Skin and cartilage have a low blood and nutrients supply. They
are also simple structures, which why they can be replaced very well.
- Adherent (circulating) cells: cells that require attachment to a surface or ECM through
specialized structures call focal adhesions for growth, survival and proliferation.
Examples: fibroblasts, endothelial cells, epithelial cells, smooth muscle cells. When
blood cells are used to create tissues, they need to be adapted to function as
adherent cells.
- Non-adherent (circulating) cells: can grow freely in solution. Examples: immune cells
such as lymphocytes, macrophages and red blood cells.
- Visualizing living cells is done by vital imaging -> observing living cells.
- Cells can adhere to their environment. This can result in deformations. Cells are
visco-elastic. A tissue cell is stiffer compared to non-adherent cells. If a cell is stuck to
a flat surface, the secretion surface is bigger.
- Cell motion (/migration): process by which cells move from one location to another.
, 1. Extension: the cell extends part of its membrane
forward in the direction of movement. This is done by
polymerization of actin filaments in the cytoskeleton.
Two types of extension: 1. Lamellipodia: broad, flat
membrane extensions at the leading edge of the cell.
2. Thin, spike-like extension that sense the
environment and guide the direction of migration.
2. Adhesion: The cell establishes focal adhesions. This
happens through integrins.
3. Retraction: older focal adhesions are disassembled
and the trailing edge retracts. This allows the cell to
free its tail and move forward.
- Cell membrane: viscous, double layer of phospholipids
including proteins, carbohydrates and cholesterol, very
flexible, allows active and passive transport. It is a
division between inside and outside.
- Cytoplasm: Gel-like, visco-elastic material containing
cytosol, organelles, vesicles, and cytoskeleton.
- Cytoskeleton: support the structure of the cell and has 3
fibrillar protein types:
1. Actin
2. Intermediate filaments
3. Microtubules
- The cytoskeleton movement is important for cell division, migration
and transport. It requires dynamic filaments and molecular
motors. The organization and mechanical properties of
actin/microfilaments are important for cell function.
Filaments form compact fiber bundles or loose networks.
They play a role in cell contraction, movement, transport
and the cell phenotype. They are linked to the ECM through
integrins (focal adhesion points).
- F-actin forms stress fibers in adherent cells. The stress
fibers can pull at the environment using the focal adhesion
points. The extracellular surface (hydrogel) dictates the
stiffness of these stress fibers.
- The formation of stress fibers:
1. Stress fibers consist of bundles of actin filaments, aligned in parallel. They are
connected by crosslinking proteins. Myosin II motors is a motor protein that can
“walk” along actin filaments. They pull together the actin filaments, creating
contractile forces in the cell.
2. Stress fibers can contract and create tension.
3. The formation of stress fibers is controlled by a
signaling pathway that involves the small GTPase
protein called RhoA, which regulates actin
cytoskeleton, when activated -> promotes contractile
function.
4. Stress fibers are essential for cell adhesion to the
substrate, contractile tension and changes in cell
shape.
,- Intermediate filaments are rigid stable elements, they provide tensile strength to the
cell. It concerns anchor cells or cells with matrix.
- Microtubules, thick filaments:
Hollow Fibers of tubulin microfilaments
Connected to centrosome, near nucleus
Movement and transport
Determine cell shape and distribution of organelles
- Nuclear lamina can be missing, which causes rapid ageing and weakness of cells.
The nucleus is linked to the environment of the cell via these laminas. A stiff external
environment causes stress fibers to pull, which leads to pulling apart of the nucleus
and apoptosis.
- Cell-cell and cell-matrix connections provide a continuous network between ‘intra’
and ‘extra’ cellular environment. The cellular micro-environment = ‘niche’.
- The matrix can control cell fate:
• cell-matrix interactions
• matrix stiffness
• matrix molecules
• Soluble signals
- The cell shape and function in tissue morphogenesis (develop shape) is determined
by:
Substrate flexibility -> stiff substrate = more contractile -> soft substrate = less
contractile.
Ligand type -> influences how the cell moves and what it becomes
Ligand density -> high density = strong attachments, more tension -> low density =
weak attachments, less spreading/tension.
- Cells determine matrix synthesis and degradation by cell-matrix reciprocity: the cells
control their matrix and the matrix controls the cells. The cell produces molecules and
can break down its own environment. Cells are shielded from force by their ECM.
- Cell maintain and repair the tissue, they produce their
own matrix (ECM) and they control it. The fibrillar
components are: collagen, elastin and GAGs. ECM is
relevant for structure, function, adaptation and
remodelling. The ECM also exists of fibronectin,
laminins and proteoglycanen.
- Triggers for growth or proliferation:
◦ Based on ‘supply and demand’
◦ To ‘reach homeostasis’
◦ Physical limitations: Ratio cell size / nuclear size
◦ Stimuli originate in cytoplasm (intrinsic)
◦ Stimuli from extracellular environment (‘molecular signaling’ and mechanical cues)
, - Interstitial growth = produced by division and activity of mature
cells (in the whole tissue).
- Appositional growth = Growth on a local location in the tissue.
- Growth: cell division. Not all cells divide and grow at the same
time (though the ‘first cells’ will do). Also not all cells and tissues
grow at the same rate, but growth is controlled.
- Cells stop growing when they touch each other (contact
inhibition). This results in the formation of a monolayer. However, when
there are cancer cells, they grow on top of the layer. It leads to a focal
point (focus).
- Tissue growth and homeostasis occurs either via stem cell division or
via ’normal’ cell division.
- Stem cells can renew itself indefinitely (‘self-renewal’) and upon division
can turn into another cell type. But has a low turnover, because they
divide infrequently under normal conditions. Adult stem cells have a low
turnover, but embryonic stem cells have a high turnover, as they are
involved in rapid growth.
• Totipotent (stem)cells: can differentiate into all cell types: the egg and
sperm cells and the first cell divisions of the fertilized ovum.
• Pluripotent (stem) cells: can differentiate into most cell types.
• Multipotent (stem)cells [purple]: can differentiate into many/several cell
types, usually of the same organ
• Differentiated, unipotent cells [blue]
• Terminally differentiated cells [yellow]
- Stages of development:
1. Embryonic growth and differentiation
2. Postnatal growth, more increase in mass compared to differentiation.
3. Maturation; equilibrium between growth and
differentiation, synthesis and degradation;
maintenance of tissue function -> homeostasis.
4. More degradation; degeneration of function.
- Growth:
• By proliferation and activity of differentiated cells.
• By proliferation of stem cells that maintain the tissue.
- Proliferation is the increasing amount of cell, while differentiation is about gaining a
special function.
- Homeostasis is the balance between synthesis and degradation.
Ongoing proliferation of cells or tissue specific stem cell:
maintenance. In case of damage: tissue repair.
- Senescence: cell permanently stops with differentiating, but does
not die.
