Abstract 257: Cortical Bone Stem Cell-Derived Exosomes Alter Wound Healing Response in Cardiac Fibroblasts and Cardiac Endothelial Cells

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Giana Schena ◽  
Hajime Kubo ◽  
Yijun Yang ◽  
Eric Feldsott ◽  
Giulia Borghetti ◽  
...  
2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Giana Schena ◽  
Hajime KUBO ◽  
Eric Feldsott ◽  
Alaina Headrick ◽  
Keith Koch ◽  
...  

Rationale: Heart failure is the one of the leading causes of death in the United States. Post-myocardial infarction is followed by cardiac remodeling that involves extensive fibrosis and ultimately progresses into heart failure. We have seen improvements in scar size and cardiac function as a result of administration of cortical bone stem cell-derived (CBSC) exosomes. Objectives: We investigated the mechanism through which CBSC-derived exosomes altered wound healing and reduced scar formation through in vitro experimentation. We continue to broaden our understanding of how CBSCs exert their anti-fibrotic effects. Methods and Results: We cultured adult rat ventricular fibroblasts and adult human cardiac fibroblasts and treated them +/- TGF β with mouse and human CBSC-derived exosomes, respectively. We saw a dose-dependent decrease in myofibroblast activation with increasing concentrations of mCBSC and hCBSC exosomes, with 100 fold decrease compared to baseline fibroblast activation in hCBSC treated cardiac fibroblasts (9.5 x 10 5 of 1.6 x 10 7 intensity), and by 40% in mCBSC treated cardiac fibroblasts (2.4 x 10 5 of 1.0 x 10 6 intensity). In the presence of TGFβ and 2.0 x 10 6 exosome particles/cell treated, the αSMA levels were still reduced by nearly 50% vs TGFβ alone (1.2 x 10 6 of 2.2 x 10 7 intensity). We performed RNA sequencing on both the rat and human cardiac fibroblasts in order to discover which fibrosis-related genes were being altered by CBSC exosomes treatment. Conclusions: Our findings show that the wound healing induced by CBSC exosome treatment post-MI involves the reduction of myofibroblast activation and decreasing the production of pro-fibrotic mRNA in cardiac fibroblasts and cardiac endothelial cells.


2020 ◽  
Vol 134 (16) ◽  
pp. 2189-2201
Author(s):  
Jessica P.E. Davis ◽  
Stephen H. Caldwell

Abstract Fibrosis results from a disordered wound healing response within the liver with activated hepatic stellate cells laying down dense, collagen-rich extracellular matrix that eventually restricts liver hepatic synthetic function and causes increased sinusoidal resistance. The end result of progressive fibrosis, cirrhosis, is associated with significant morbidity and mortality as well as tremendous economic burden. Fibrosis can be conceptualized as an aberrant wound healing response analogous to a chronic ankle sprain that is driven by chronic liver injury commonly over decades. Two unique aspects of hepatic fibrosis – the chronic nature of insult required and the liver’s unique ability to regenerate – give an opportunity for pharmacologic intervention to stop or slow the pace of fibrosis in patients early in the course of their liver disease. Two potential biologic mechanisms link together hemostasis and fibrosis: focal parenchymal extinction and direct stellate cell activation by thrombin and Factor Xa. Available translational research further supports the role of thrombosis in fibrosis. In this review, we will summarize what is known about the convergence of hemostatic changes and hepatic fibrosis in chronic liver disease and present current preclinical and clinical data exploring the relationship between the two. We will also present clinical trial data that underscores the potential use of anticoagulant therapy as an antifibrotic factor in liver disease.


1993 ◽  
Vol 20 (3) ◽  
pp. 465-472 ◽  
Author(s):  
Thomas A. Mustoe ◽  
Beatriz H. Porras-Reyes

2007 ◽  
Vol 48 (5) ◽  
pp. 2068 ◽  
Author(s):  
Christian Meltendorf ◽  
Guido J. Burbach ◽  
Jens Bu¨hren ◽  
Reinhold Bug ◽  
Christian Ohrloff ◽  
...  

2020 ◽  
pp. 23-33
Author(s):  
Mawada M. Funjan

Many researches focused on laser therapy of wound healing in different animal models due to the lack of a standard protocol in the application of such phototherapy. Objective:  To study the effects of 810nm laser at a constant irradiance of 41.63 mw/cm2 and exposure (illumination) time of 5,15  minutes on wounds created on Albino mice (BALB/c).      Skin wound with elliptic shape and full thickness was created on the dorsal side of  ‘45 mature male albino mice. Irradiated animals were divided into two main groups based on irradiation time, the first was irradiated for 5 min and the second for 15 min, each was subdivided into three subgroups (n=5) according to number of treatment days (3, 5 and 10 days).   Both treated and respective control (n=15) subgroups were sacrificed on days 3, 5 and 10 posttreatment.  Laser therapy was applied using a 810 nm diode laser with a continuous wave, an output power of 400 mw, and irradiance of 41.63. The 5 min dose was 12 .5 J/cm2, whereas the 15 min dose was 37.4 J/cm2. The shape of the laser beam was fitted with a convex lens as ‘beam expander’ to irradiate a circular area of 3.4 cm diameter. Laser therapy was started after surgery and repeated for 3, 5 and 10 days, while its effects were examined by histological evaluation. Results:  At day 3 of treatment with near infrared 810nm laser at doses of 12.5J/cm² and 37.4J/cm², there was no evidence of wounds healing in irradiated groups which showed no differences with the respective control groups. At day 5 of treatment, the results showed an important increase in the scores of the parameters of wound healing (formation of granulation tissue and collagen deposition) in the irradiated groups. Near infrared 810nm laser had photobiostimulation effects on wound healing at irradiance of 41.63mW/cm² and doses of 12.5J/cm² for 5 minutes and 37.4J/cm² for 15 minutes exposure time. A complete picture of wound healing response appeared in all irradiated groups within 10 days of treatment, as expressed by complete ‘re-epithelialization’, moderate granulation tissue formation, and presence of collagen fibers, while incomplete wound healing response was observed in un-irradiated control groups within the same period. The study showed that 810 nm laser therapies had significant effects on wound healing, especially at a dose of 37.4J/cm².


Cornea ◽  
2019 ◽  
Vol 38 (12) ◽  
pp. 1582-1588 ◽  
Author(s):  
Yuan Sun ◽  
Ting Zhang ◽  
Manli Liu ◽  
Yugui Zhou ◽  
Shengbei Weng ◽  
...  

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