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									                                                                             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


        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.

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