Author Interviews, FASEB / 08.08.2017

Substances in Spit May Help Wounds Heal Faster

MedicalResearch.com Interview with: Vicente A. Torres PhD Associate Professor Institute for Research in Dental Sciences Faculty of Dentistry Universidad de Chile  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Wounds in the oral cavity heal faster and more efficiently than skin. This is in part due to saliva. However, the reasons underlying these differences remain poorly known. Since blood vessel formation (i.e. angiogenesis) is critical to the success and efficiency of wound healing, we focused our studies on the effects of saliva, and specifically the salivary molecule, histatin-1, on angiogenesis. Our studies showed that histatin-1 promotes angiogenesis, as observed in experiments performed at three "levels": 1) using human cell cultures (endothelial cells, which are cells that form blood vessels), (2) using chicken embryos, as animal models, and (3) analyzing saliva samples obtained from healthy donors. With all these models, histatin-1 and saliva were found to increase blood vessel formation. In addition, our studies provide information about the molecular mechanisms (i.e. signaling pathways) whereby endothelial cells respond towards histatin-1, by increasing their migration and adhesion to the extracellular matrix.
Author Interviews, Dermatology / 01.06.2017

MedicalResearch.com Interview with: [caption id="attachment_34984" align="alignleft" width="200"]Jean-François Cailhier, M.D., Ph.D., FRCP(c) Professeur Agrégé de Clinique/ Associate Professor Département de Médecine, Faculté de Médecine Université de Montreal Dr. Jean-François Cailhier[/caption] Jean-François Cailhier, M.D., Ph.D., FRCP(c) Professeur Agrégé de Clinique/ Associate Professor Département de Médecine, Faculté de Médecine Université de Montreal MedicalResearch.com: What is the background for this study? What are the main findings? Response: Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8) is released by apoptotic cells and activated cells in the skin. Its effect on endothelial cells and pericytes was previously reported to accelerate wound healing. In our wound healing model, we demonstrated that MFG-E8 was important to reprogram skin macrophages into pro-repair cells. Moreover, we demonstrated that administration of exogenous MFG-E8 was able to accelerate wound healing in WT and MFG-E8 KO mice by generating M2 macrophages. Furthermore, to highlight to importance of MFG-E8 on macrophage reprogramming, adoptive transfer of MFG-E8-treated macrophages also promoted wound healing. These pro-repair effects seem to be dependent on the production of a crucial fibroblast growth factor, basic Fibroblast Growth Factor (bFGF), by macrophages which promoted fibroblast migration and proliferation.
Author Interviews, Dermatology, Technology / 11.08.2016

MedicalResearch.com Interview with: Alexander Golberg, PhD Senior Lecturer Head of Environmental Bioengineering Laboratory Porter School of Environmental Studies Tel Aviv University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Wound care costs the U.S. healthcare system more than $20 billion each year, and care required to combat skin scarring represents an additional $12 billion burden. Hypertrophic scarring after trauma and burn injury remains a major clinical challenge that leads to physical, aesthetic, functional, psychological, and social stresses in thousands of patients. This is a stubborn clinical problem very difficult to solve. Inspired by previous works that pulsed electric fields kill cells precisely in tissue (procedure called irreversible electroporaiton, developed by UC Berkeley group of Boris Rubinsky and Rafael Davalo) and these ablated tissues regenerate with minimal scarring, we decided to test whether pulsed electric fields can reduce the scar formation if we treat the wound during healing. We found that partial irreversible electroporation using 200 pulses of 250 V and 70 µs duration, delivered at 3 Hz every 20 days during a total of five therapy sessions after the initial burn injury resulted in a 57.9% reduction of the scar area in comparison with untreated scars and structural features approaching those of normal skin. Noteworthy, unlike humans, rats do not develop hypertrophic scars. Therefore, the use of a rat animal model is the limiting factor of this work.
Author Interviews, Dermatology, Nature / 23.02.2015

Chwee Teck (C.T.) LIM PhD Provost’s Chair Professor, Deputy Head, Department of Biomedical Engineering & Department of Mechanical Engineering Principal Investigator, Mechanobiology Institute Faculty Fellow, Singapore-MIT Alliance for Research & Technology (SMART) National University of Singapore Faculty of Engineering, SingaporeMedicalResearch.com Interview with: Chwee Teck (C.T.) LIM PhD Provost’s Chair Professor, Deputy Head, Department of Biomedical Engineering & Department of Mechanical Engineering Principal Investigator, Mechanobiology Institute Faculty Fellow, Singapore-MIT Alliance for Research & Technology (SMART) National University of Singapore   Medical Research: What is the background for this study? What are the main findings? Professor Chwee Teck Lim: Epithelial cells have a natural tendency to close gaps and this feature plays a crucial role in many biological processes such as embryological development and wound healing. For example, skin does consist of epithelial cells that when wounded, will elicit closure to initiate healing.  How epithelial cells close such gaps has always fascinated researchers from across many disciplines. It is generally accepted that two major mechanisms exist that underlie such a closure. The first is a "cell-crawling" mechanism wherein cells at the edge of the gap actively send protrusions or lamellipodia and use them as footholds to migrate over the gap. However, such a migration requires that the gap is conducive for cells to attach and form adhesions or footholds. The second mechanism is based on a coordinated contraction of multiple bundles of cellular cytoskeletal components (bundles of actin) in a manner similar to that of a "purse-string". Despite many studies, it has always been difficult to understand and characterize these processes separately since most often they co-exist. In this study, we show that keratinocyte monolayers have a tendency to close circular non-adhesive gaps (gaps that have been coated with a polymer that does not allow cells to adhere or form foot-holds) through contraction of bundles of actin within cells at the edge of the gap. We find that such as closure is strongly affected by the size of the gap (gaps more than 150 um in diameter have a tendency to close only partially), curvature of the gap (gaps with high curvature show better closure), and strength of intercellular adhesion (poor intercellular adhesion completely inhibits closure of non-adhesive gaps).
Aging, Author Interviews, Dermatology / 03.01.2015

David Granville, BSc, PhD, FAHA Professor, University of British Columbia Scholar of the Royal Society of Canada Director, GEM Facility, Centre for Heart Lung Innovation, St. Paul's Hospital Founder and CSO, viDA Therapeutics, Inc. Vancouver, BC, CanadaMedicalResearch.com Interview with: David Granville, BSc, PhD, FAHA Professor, University of British Columbia Scholar of the Royal Society of Canada Director, GEM Facility, Centre for Heart Lung Innovation, St. Paul's Hospital Founder and CSO, viDA Therapeutics, Inc. Vancouver, BC, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Granville: My background is in cardiovascular research. In particular, how age affects blood vessels and how age affects mechanisms of blood vessel and heart injury and repair. We became interested in skin aging during a study in which we were studying the role of a protein degrading enzyme known as Granzyme B in atherosclerosis (hardening of the arteries) and aging. In these studies, we were using a genetic mouse model that is prone to accelerated aging, and knocked out Granzyme B. Although we were initially focused on the blood vessels, we also found that Granzyme B-deficient mice exhibited younger-looking skin. As we started to look into this, we became aware that UV light can induce the skin cells to produce Granzyme B. As sunlight is believed to be responsible for 80-90% of preventable skin aging, we generated a solar-simulated light box (with the similar ratios of UVA/UVB to sunlight) to assess whether Granzyme B played a role in UV-induced skin aging (aka photoaging). We exposed the mice to repetitive, low dose UV three times per week for 20 weeks. After 20 weeks we observed that Granzyme B deficient mice exhibited fewer wrinkles. We then wanted to look histologically and biochemically into how Granzyme B was affecting skin morphology. Granzyme B deficient mice exhibited greater collagen density compared to mice that possessed Granzyme B. As we looked into the mechanism in more detail, we determined that Granzyme B was cleaving a protein known as decorin. Decorin is responsible for collagen fibrillogenesis and assembling collagen into tight bundles. Loss of decorin is associated with a loss of collagen tensile strength. Interestingly, decorin also protects collagen from destruction by a protein-degrading enzyme known as MMP1. We showed in the study that by breaking down decorin, Granzyme B renders collagen susceptible to MMP1-mediated degradation. In addition, we showed that Granzyme B-fragmentation of another protein, fibronectin, led to the upregulation of MMP1 in skin fibroblasts. In summary, the paper showed that UV induced Granzyme B expression in the skin and showed that this enzyme contributes to the breakdown of extracellular matrix proteins and formation of wrinkles. A link to the Aging Cell publication: http://onlinelibrary.wiley.com/doi/10.1111/acel.12298/pdf
Author Interviews, Dermatology / 06.10.2014

Conor L. Evans, PhD Assistant Professor Harvard Medical School Wellman Center for Photomedicine Massachusetts General Hospital Affiliate Faculty, Harvard University Biophysics Program Charlestown, MAMedicalResearch.com Interview with: Conor L. Evans, PhD Assistant Professor Harvard Medical School Wellman Center for Photomedicine Massachusetts General Hospital Affiliate Faculty, Harvard University Biophysics Program Charlestown, MA Medical Research: What are the main findings of the study? Dr. Evans: The main finding of this research is that topically applied rapid-drying wound dressings containing optical sensors for oxygen can be used to quantify skin oxygenation status in a way that reflects the viability of the underlying tissue, and therefore has the potential to aid in the clinical care for patients with burns, grafts and various other skin conditions.