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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 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.
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