Day 1 :
University Paris-East Creteil
Keynote: The heparan sulfates mimics (RGTA) and their uses in skin healing : A translational medicine saga
Time : 09:30-10:15
Denis Barritault graduated in Physics, completed his PhD in biochemistry in Paris University. Post-doctoral in molecular immunology at Pasteur Institute and NYU as NIH Fogarty Fellow he joined INSERM unit in Paris as developmental biologist. He made the first description and patents of FGF extracted from retina in 1979 and 82 as skin and cornea healing agent, became full professor at Paris-East University in 1985, founded and directed a CNRS Laboratory on cell and tissue regeneration until 2003. He is now President of OTR3, Emeritus professor, honorary director CRRET CNRS unit and author in over 200 publications and 30 patents. He succeeded in transforming his research in basic science into product to treat patients; one to treat skin wound the other for corneal ulcer. Several other products are now in development for new indications in regenerative medicine
Background: Matrix therapy is a newly coined name to emphasis the importance of the extracellular matrix in regenerative medicine. Heparan sulfates (HS) are key elements of the extracellular matrix (ECM) scaffold, which store and protect most growth factors/cytokines controlling the cell migration and differentiation required for healing processes. Tissue injury will lead to destruction of cells and surrounding ECM with resulting scars or fibroses. We have engineered biodegradable nano-polymers (alpha 1-6 polyglucose carboxymethyl sulfate) mimicking (RGTA) to replace destroyed HS in the damaged ECM scaffolding and to protect cytokines produced by healthy neighboring cells, thereby restoring the ECM microenvironment and tissue homeostasis. This matrix therapy approach has considerably improved the quality of healing in various animal models with reduction or absence of fibrosis resulting in a regeneration process. The RGTA technology validated in many preclinical studies is now marketed as human healing agents for corneal and for skin ulcers, the later under the trade name of CACIPLIQ.
Results: As of today over 30000 of patients with unfavorable therapeutic outcome have benefit from CACIPLIQ, most leading to wound closure and with no record of adverse effect. A friendly user and cost effective spray form (CACIPLIQSPRAY) is now available providing a larger user access to all types of wounds.
Cochrane analysis tends to demonstrate that RCT in wound care poorly demonstrate efficacy. RCT may not be appropriated in this field as when all best conditions are met natural skin healing will occur and the time to heal in a “RCT controlled wound environment” will reflect internal biological clocks more than external outputs such as product efficacy.
In “real clinic life” RCT conditions do not exist, benefit of CACIPLIQ is better illustrated by reducing the economic burden of hard-to-heal wounds
University of Maryland, USA
Time : 10:15-11:00
Shaik O Rahaman is an Assistant Professor at the University of Maryland, USA. His laboratory is interested in elucidating the signaling events underlying the pathogenesis of atherosclerosis and fibrosis. Dr. Rahaman earned his PhD in Molecular Biology at Jadavpur University, and a BS in Human Physiology (Honors), and an MS in Biophysics and Molecular Biology from University of Calcutta. From 2000-2014, Dr. Rahaman worked at Cleveland Clinic, Cleveland, USA, as a Postdoctoral Fellow, eventually as a Project Scientist and Assistant Professor. In 2013, he was the recipient of the American Heart Association Scientist Development Grant. Dr. Rahaman is the author or co-author of 21 research papers in high impact international peer-reviewed journals of repute. Dr. Rahaman has given numerous invited talks nationally and internationally, and is a reviewer/editorial board member in numerous scientific journals. Dr. Rahaman also served as a reviewer for National Institute of Health (USA).
Scleroderma or systemic sclerosis (SSc) is a multisystem idiopathic connective tissue disease with high morbidity and mortality. SSc is characterized by immune, inflammatory, vascular, and fibrotic manifestation in numerous organs including skin and lung. There are no effective medical treatments available and the exact cause remains poorly understood for SSc. Fibroblast differentiation into myofibroblast is a critical process in SSc and other fibrotic diseases. Emerging data support a role for both a mechanical signal, e.g., matrix stiffness, and a biochemical signal, e.g., transforming growth factor (TGF) beta1, in fibroblast activation, migration, and differentiation. Published work by our group and others showed that TRPV4, an ion channel in the transientreceptor potential vanilloid family, a known mechanosensor, is activated by a range of mechanical and biochemical stimuli. We have obtained evidence that: i) increased numbers of TRPV4 positive myofibroblasts are present in dermal tissues of patients with SSc compared to healty controls ii) TRPV4 deletion in mice prevented skin fibrosis development as assessed bydermal thickness, subcutaneous fat deposition, macrophage accumulation, myofibroblast abundance, and collagen deposition in skin in a bleomycin model of SSc iii) genetic ablation or pharmacologic antagonism of TRPV4 abrogates both matrix stiffness and TGFbeta1-induced dermal fibroblast differentiation and iv) TRPV4 regulates pro-fibrotic TGFbeta1 actions in a Smad-independent but PI3K-AKT-dependent manner. Altogether, these results, showed that TRPV4 calcium-permeable channel mediates fibrogenesis in SSc. Successful manipulation of the TRPV4 activity may be a targeted therapeutic approach to the treatment of SSc and other fibrotic diseases.