Epidermis -- Time Dimension of the Skin
WHAT IS IT?
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Think of your friend. You meet him frequently and his appearance seems
always the same. Yet his unchanging appearance hides a world in flux. His
body is made of cells. Some are born, others are dying, yet the organism
maintains the same appearance. The following model is a glimpse into this
fascinating world of flux. It serves two additional purposes. It
illustrates a new way to teach Histopathology (the science of cells and
tissues in the body). Finally it highlights an ancient philosophy.
Let's examine this artificial skin, and see how it behaves.
HOW TO USE IT
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'setup' button: Clears the display window and creates a blue
stem cell.
'go' button: Starts the simulation.
'Create a new unit' button: Adds a new stem cell to the skin.
'Chemotherapy' button: Kills supra-basal cells.
'Suntan' button: Exposes the skin to the sun.
'Bruise' button: Bruises the skin.
Two monitor tools display time and the number of skin units (unit-count)
'Display-skin-patch' switch: When set to 1, displays a skin patch.
A Plot window displays the total cell count in the skin.
The model simulates only the upper covering of the skin called epidermis.
Its layers are displayed in the interface window. Basal layer is the
deepest. The upper cornified covers the skin. It becomes apparent to you
when observing the skin.
THINGS TO NOTICE
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Set 'Display-skin-patch' switch to 0.
Click on setup. A blue skin stem cell appears.
Click on 'Go' and watch the skin unit elongating.
Stem cells and transitional cells.
Only the stem cell is dividing. Following its division one of its progeny
replaces the parent cell and remains a stem cell. The other is pushed
upward and is called transitional cell. Stem cell division generates a cell
stream upward. Cells age as the go and when their time has come they die
and are sloughed off the unit top.
Start again. Click off the go button, then click on setup and go. Watch
the unit growing. As long as cell production rate exceeds the death rate,
the unit elongates. When cell production equals the rate of cell death,
the unit maintains a constant length.
THINGS TO TRY
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Create a new unit (click on the so named button)
A new stem cell is formed and it generates a new unit. Continue adding
about 15 units. What you see is the cross section of the upper skin part
called epidermis. Each layer has a name (given in the interface window).
You just simulated the growth of the skin of a child. In the growing child
the skin expands by creating additional units. Stem cells divide in two
modes: In each unit the stem cell divides asymmetrically, since generating
two different cells, a stem and a transitional. When a new unit is added
the stem cell divides symmetrically, into two stem cells. In the adult,
stem cells do not divide symmetrically.
Differentiation
Cells in each layer perform specific tasks. Notice that each layer is a
station in the upward movement of a cell. When born it is green (called
supra basal) . Then it turns into a yellow (spinous) cell. Later it becomes
a granular (violet) cell. At old age it turns into a cornified cell and
then sloughs off the skin. The scales that may seed your hair, are dead
cornified cells.
The change in cell appaerance and its tasks is called differentiation. Skin
cells differentiate as they go. Notice that differentiation and aging are
equivalent. Cell aging may be viewed as differentiation.
Click on 'Bruise'
When you bruise your skin, the upper layers are torn off. This condition is
called erosion. Examine the plot window after bruising. As cells move
upward the erosion heals. This is known also as skin regeneration.
Click on 'Chemotherapy'
Chemotherapy kills mainly supra basal cells. A slit of dead cells gradually
moves upward. As long as it exists, the skin is fragile and may slough off,
which generally does not happen. You may have heard that following
chemotherapy the patient loses its hair. The mechanism is similar. The
suprabasal cells of the hair follicle are killed and the hair falls out.
Suntan
Notice the black lines extending from the lower skin layer. These cells are
called melanocytes. When exposed to intensive sun shine, they color all
neighboring skin cells. Click on 'Suntan'. Repeat clicking and notice the change.
After leaving the beach to your home, colored cells continue streaming
upward. When they die you lose your suntan.
Examine the skin patch.
The model displays a microscopic cross section of the epidermis. When
watching your skin you actually see only the upper layer. In order to watch
the skin from above, set the 'display-skin-patch' switch to 1. Repeat the
above experiments and watch its changing color. The real skin has a
different color palette, yet undergoes similar changes.
It is instructive to click on 'Suntan' and watch the patch.
Cells stream
What drives skin cells upward, remains a puzzle. They are neither pusheded,
nor pulled, they simply stream.
Now return to your friend. Although his appearance seems unchanged, you
know that his epidermis continually changes. Not only the skin. Almost all
cells in the body stream. They are born during a stem cell division and
gradually stream toward their graveyard.
Panta Rhe
About 500 years BC a philosopher named Heraclitus said: "Everything streams
(Panta Rhe in Greek). You never step into the same river twice". Now we may
add, "You never meet the same person twice".
The model
Cell attributes (turtles-own):
Age :
age1: The maximal age a cell attains
stem : In stem cells, stem = 1. In transitory cells, stem = 0.
progeny: Each symmetric stem cell division creates a new progeny
(setprogeny progeny + 1)
color: Stem cells are blue.
In transitory cells color represents age. (setc yellow + 0.4 * age)
melanocyte: Black cells situated among the lower layers.
melanin: Stores brown color. (setmelanin 35 setc melanin)
patches-own [skin?] Displays the skin as viewed from above
Global parameters:
time: system time.
tima: involved in controlling the speed of events.
step: the minimal time unit (setstep 0.5).
cell-count:
unit-count: Cell number in a unit.
max-count Maximal attainable unit length
Routines
setup calls: set-stem, set-patch, set-plot-count
set-stem
creates two cells:
who = 0 is a dummy cell that stores attributes
for coloring the skin patch (stestem 100)
who = 1 generates other stem and transitional cells (ststem 1)
set-patch represents the skin as viewed from above.
one-step: performs functions that occur in one step:
increments time and age by one step, moves cells, calls
mitosis and death routines.
It is controlled by a 'go' routine that slows down the speed
of events.
go: increments tima by one step, and if (tima mod 20 = 0) [one-step],
it calls 'one-step'. In order to speed events replace
Ô20Õ by a smaller number and vice versa
new-unit: Creates a new stem cell (symmetric stem cell division).
Every fifth unit is made of melanocytes.
if (progeny mod 5) = 0 [setc 2 setmelanocyte 1]
move-transitional-cells: Color is proportional to age (setc yellow + 0.4 >>* age)
granulosum and corneum are colored separately.
skin-color: colors the patch. At each step color is stored in the dummy
cell; (who = 0), that transfers it to the patch.
mitosis: hatches a supra basal (green) cell (transitional) It is an
asymmetric cell division.
The rate of mitosis is controlled in 'one-step'. It depends on
the cell count in the unit. (if unit-count < max-count [mitosis]).
death: Death rate depends on the cell count in the unit. Age1 determines
the maximal age attained by a cell.
Since max-count is given age1 cannot exceed 20.
(setage1 min 18 + (random 4) - 2 ((max-count / 2) - 2)
evaluate-params Counts cells and units
STARLOGOT FEATURES
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REFERENCES and CREDITS
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This model was contributed by:
Gershom Zajicek M.D.
Professor of Experimental Medicine and Cancer Research
The Hebrew University-Hadassah Medical School Jerusalem.
gzajicek21@aol.com
Date: March 15, 1999.
Temporary address:
Burgplatz 1
71522 Backnang, Germany.
Tel +49-7191- 84 043
Fax +49-7191-950 221
E-mail: gzajicek21@aol.com
Internet: http://www.md.huji.ac.il/special/cancer/journal.html