Dynamic reciprocity and wound healing

Published on October 7, 2014   26 min
0:00
My name is Ira Herman. I am a Professor of Developmental Molecular and Chemical Biology at the School of Medicine, Tufts University in Boston, Massachusetts, where I direct the Center for Innovations in Wound Healing Research, and a graduate program in Cellular and Molecular Physiology. Today I'll be sharing some insights linked to dynamic reciprocity. And how this notion of a dynamic and reciprocal signaling network plays pivotal roles in regulating both the cellular responses to injury and control of wound healing. And why, in the context of non-healing wounds, this dynamic and reciprocal signaling between the cells of the epidermal compartment and the dermal compartments, why this dynamic reciprocity is disrupted and actually could contribute to, or be responsible for, the non-healing dynamics that are known.
0:59
So we'll begin by considering what might be a simple definition of what is dynamic reciprocity. Then, talk about how this paradigm could, and does, apply well to the notions of healing. And then talk about the extracellular matrix, and how this relationship between cells and their underlying, or surrounding extracellular matrix, contributes to the dynamics in the cellular responses that occur during reparative healing.
1:31
So on the second slide there is this is original definition, as we call it. Where did the term come from? Actually, it doesn't really derive from biological sciences, but it was actually recognized and re-coined in the context of biology by Mina Bissell and her colleagues, last century in the 1980s. And it was immediately recognized by us, and others, that dynamic reciprocity could be an important biological term to help to describe the regulatory role that the extracellular matrix plays in modulating cellular function. Regardless of whether we're talking about signals for growth, signals for differentiation, or the remodeling of tissues that take place during the development of the organism or adult life, and especially during disease, and in our case, injury and repair.
2:24
So in the next slide you'll see some words linked to how this notion, or paradigm of dynamic reciprocity, plays directly into this notion of wound healing. The cells of the epidermal compartment contribute to organize a basement membrane. That basement membrane is enriched in many, many different extracellular moieties. And those moieties feed back and give rise to signals, important signals. So it's not just that the matrix serves as a scaffold upon which cells can grow and crawl, differentiate. But in fact, the matrix is an informational reservoir that actively gives rise to information that is processed by cells. And in return, the cells respond and then contribute to what might be modulating a microenvironmental shift. So examples, not restricted necessarily or confined completely to what might be wound healing, any process in biology could be a paradigm, or a reflection, of this dynamic reciprocal relationship. Matrix production of turnover, as I mentioned cellular responses to injury cells, have two predominating responses when injury occurs. They first migrate in response, and then proliferate or change their differentiated features. There are immune modulatory roles that microbes themselves play in modifying host tissue responses, peptides that are elaborated as microbes remodel the host. Microenvironment contribute to the cellular responses displayed by the host. And this is actually a critical and important part of the host response to injury. And then, for example, within the dermal compartment, as we know well, one cannot do any healing whatsoever without an adequate blood supply. The delivery of nutrients in exchange for metabolites takes place at the control of the vasculature, our epidermis, or the skin proper that we see when we look at people walking down the street. The epidermal compartment is avascular and derives all of its nutrients from the underlying dermal microvasculature. So again, this notion of dynamic and reciprocal signaling, what are the blood vessels sensing? How are they sensing the injury? And then, how are they responding to give rise to a reparative response in the healing and closed wound?
4:48
So in the next slide is a very old cartoon derived from the early literature. And contained within a paper that Greg Schultz and others, including myself, contributed to the scientific literature a few years ago. And it's cited on the bottom of this particular slide. And again, it's this sort of ying and yang notion of what cells do contributes to changes in the microenvironment. And those changes in the microenvironment feed back on cells to alter their adaptive responses. So whether we're talking about synthetic processes, or degradative processes, processes that reflect what might be a more pangenic event during the development. Things that are changing shape, for example, as a developing organism changes shape continually to take on its adult forms. And dynamic and reciprocal signaling may not necessarily be confined solely to chemicals. There are chemomechanical views that give rise to changes in polarity and differentiation, and as I mentioned, migration growth, as well as survival.
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Dynamic reciprocity and wound healing

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