Dan Pincus
Tissue Engineering, Dr. Keith Gooch
April 3, 2001
Paper Rewrite
Cell Migration and Wound Healing
What happens when you cut yourself? First you hurt, then you bleed, then a scab
of dried blood forms, and in a few days or weeks, you’re all better. For all the service
that our skin provides us, it’s surprising how little we consider what a marvelous capacity
we have to heal our own wounds. But how does this happen? How does the body know
that the skin is cut? How does it know what to do? And how does it do it?
These questions are fast being addressed by the bioengineers in the new and
exploding field of Tissue Engineering. Tissue Engineers seek to uncover the mechanisms
by which cells of the embryo grow into a wide variety of specialized cells to form and
maintain tissues. The structure of the specialized cells in the tissues is of critical
importance to the function of the tissue it composes–one can imagine how important the
structure of the brain is for thought or the heart is for pumping blood. In order to create
and keep the organization, cells migrate according to many cues given to them by the
body. Understanding and manipulation of cell migration is one of the holy grails of
Tissue Engineering, and the ability to control the migration of cells is critical to complex
functions, like wound healing. When tissue is damaged, as in a wound, the healing
process depends greatly on the proper migration of cells, as we’ll see in the following
discussion.
When the skin is first broken, the body’s first response is to make a temporary
plug called a clot from blood-derived substances. The clot prevents any outside
substances from causing an infection. The blood usually comes from blood vessels that
are broken along with the skin. Some cells of the blood secrete a thick web of fibers
called fibrin. Other blood cells called platelets get trapped in the fibrin clot, and slowly
degrade and release their cytokines. Cytokines are cell-signaling proteins that direct the
interaction and movement of cells. These cytokines are necessary because the next step
in wound healing will depend greatly on recruiting the proper cells from around the body
to come and fix the wound.
Within minutes of clot formation, cells called neutrophils and the macrophages
migrate from the blood stream to the wound site in response to the clot’s cytokines.
Their role is to clear all the bacteria or any other unwanted organisms at the site,
including unwanted human cells. Once their role is complete, the macrophages and
neutrophils release more cytokines to amplify the previous migratory response.
The next step is reepithelialation, or making new skin cells. The keratinocyte, or
skin cell, closest to the clot is called the leading-edge keratinocyte. Its role is two-fold: 1)
to dissolve the fibrin clot by secreting clot-dissolving substances and 2) to migrate and
reproduce to form a new layer of healthy skin beneath the clot. When the leading-edge
keratinocytes on either side of the clot meet, they know to stop migrating. Now with a
single layer of keratinocytes beneath the clot, the keratinocytes reproduce to create a
normal, healthy, multi-layered skin.
The selective migration of specific cells is a critical activity in many human
functions. The appropriate cells must be recruited at the appropriate time and move
around the wound to perform their task. Tissue Engineering faces many challenges in
creating tissue that has the ability to migrate when necessary or to recruit the appropriate
migrating cells to them. Without it, functions like wound healing would be impossible.