Séverine Sigrist

Séverine Sigrist is a biochemist, cell biologist and neuroscientist born on June 16 of 1973 in Tours (France). Although she has participated in numerous neuroscientific articles, her main research has been based on the search for diabetes treatments. More specifically, her latest studies have focused on the creation of a bioartificial pancreas.
== Biography ==
In 1993, she graduated in biochemistry from the François Rabelais University of Tours. From 1993 to 1996 she completed a master's degree in pharmacy and biotechnology at the University of Strasbourg. Finally, from 1996 to 1999 she completed her doctorate in cell biology and neuroscience at the University of Strasbourg.
== Scientific career ==
She began her scientific career at the Centre européen d'étude du diabète (CEED) in 2000 as the head of research on Langerhans islets|Langerhans islet transplantation in the pancreas for patients with type 1 diabetes. In 2005, she was appointed head of the laboratory and initiates new research for the prevention and treatment of this disease. She is in charge of monitoring research projects, focusing on the search for collaborators, publishing and publishing articles in international journals. At the same time, she is also involved in university teaching.
Since 2014 she has been president of a group called Biovalley France that promotes innovation and competitiveness among companies dedicated to health.
Currently, Séverine is the author of more than 50 scientific publications and several patents.
=== Business project: Defymed ===
In 2011, Séverine created Defymed. It is a Startup company|start-up company that aims to research and develop Medical device|medical devices for the treatment of diabetes; Specifically, Defymed is a Corporate spin-off|spin-off company of the Centre Européen d'Étude du Diabète (CEED) that started working on the idea of ​​the bioartificial pancreas in 1996.
Devices developed by Defymed are currently in the advanced Preclinical development|preclinical testing phase.
==== Bioartificial pancreas ====
It is a medical device that encapsulates insulin-secreting cells for the treatment of type 1 diabetes.
This device consists of a flat circular bag made up of biocompatible but Non-Biodegradable|non-biodegradable membranes that allow the passage of glucose and insulin through them. They do not allow the passage of other molecules such as the molecules of the immune system, therefore, these membranes have a selective permeability. The fact that the membranes are immunoprotective (they do not allow Antibody|antibodies to pass through) avoids the need to administer immunosuppressants to cell therapy patients.File:Bioartificial pancreas with its parts.jpg|thumb|301x301px|Bioartificial pancreas
The device is made up of subcutaneous injection ports that make up an entry and exit system. These ports are attached to flexible Catheter|catheters that connect to the flat bag of semi-permeable membranes. Through the injection ports, the insulin-secreting cells can be administered, which through the flexible catheters will reach the bag of semi-permeable membranes.
The installation of this device consists of implanting it empty to allow surrounding vascularization and healing, thus avoiding cellular Hypoxia (medical)|hypoxia at the time of injection. In other words, it is interesting to have Blood vessel|blood vessels surrounding the device so that they can provide oxygen to the cells that will be inside. Once vascularized, the entry/exit system allows for easy insertion and subsequent replacement of cells without having to retrieve the entire device, prolonging its useful life and avoiding repeated Surgery|surgeries.
Therefore, this device provides unlimited access to insulin-secreting cells due to the possibility of cell substitution and the possibility of injecting Stem cell|stem cells. In this way, dependence on human donations is avoided.
In addition, this device can be used for other purposes, such as for the treatment of Haemophilia A|hemophilia A. Instead of encapsulating cells secreting insulin, cells secreting Factor VIII|coagulation factor VIII can be encapsulated. Thus, this medical device would go from being a bioartificial pancreas to being a bioartificial organ with multiple functions adaptable to different pathologies.
==== Insulin delivery device ====
It is a medical device for the physiological administration of insulin. The idea is for this device to administer insulin instantly with a Subcutaneous injection|subcutaneous intraperitoneal injection. It is composed, like the bioartificial pancreas, of a biocompatible but not biodegradable membrane with selective permeability only for insulin.
This device could be adapted to more pathologies and treatments, since, apart from insulin, it could inject Drug|drugs or other Molecule|molecules.
In January 2022, Defymed received approval to begin trial in clinical phases. The first clinical phase aims to validate the benefit of administering physiological insulin to diabetic patients as well as assessing the risks, safety, and tolerance to this new device. This first phase is expected to last about eighteen months. Specifically, this study is intended for patients with type 1 diabetes who do not respond properly to subcutaneous insulin administration and who experience large variations in blood glucose levels.
== Scientific research ==
Despite all the research, the exact causes of type 1 diabetes are still unknown. Séverine raises 3 factors: genetic factor, autoimmunity, and Environmental factor|environmental factors such as diet and Stress (biology)|stress. Regarding the food factor, she states that it is currently a problem in terms of quantity and quality. Many of today's Fruit|fruits and Vegetable|vegetables contain fewer antioxidants than before, causing the pancreatic beta cells (insulin-secreting cells) to be more affected by oxidative stress. To this we should add the use of Pesticide|pesticides in food.
As a result, much of Séverine's research focuses on Antioxidant|antioxidants.
=== Protective effect of antioxidants on diabetes ===
Diabetes increases the risk of microvascular (ex. diabetic nephropathy) and macrovascular (ex. diabetic cardiomyopathy) complications. Reduced blood flow can also cause neuropathy and retinopathy. Inflammation is also an important process in the development of complications in this disease because hyperglycemia increases the levels of proinflammatory Protein|proteins causing local and systemic inflammation.
A sedentary lifestyle, overeating and processed and sugary foods increases the risk of diabetes, as well as other factors such as smoking, alcoholism and Ultraviolet|UV rays that increase oxidative radicals causing an increase in cardiovascular complications.
The Mediterranean diet (rich in fruits, vegetables, grains, olive oil, and wine) has been shown to increase antioxidant capacity, decrease inflammation, and improve insulin sensitivity, among others. Thus, the Mediterranean diet reduces the incidence of type 2 diabetes and diabetic retinopathy. In addition, most studies talk about the benefits of antioxidant-rich natural products that protect blood vessels from oxidative stress, loss of vascular homeostasis, and diabetic complications. Therefore, studies demonstrate the ability of antioxidants to prevent or counteract excessive ROS (reactive oxygen species) production, important because ROS levels are the major determinants of altered insulin sensitivity.
=== Safety and function of the new prevascularized bioartificial pancreas in allogeneic rats ===
Prior to Defymed’s bioartificial pancreas, there were several cell encapsulation devices from other companies, but none of them hit the market due to problems during the study that made them unviable. So Séverine and her team worked to achieve a viable device with biocompatible membranes with high permeability to glucose, insulin, oxygen, and Nutrient|nutrients, with Immunoglobulin G|IgG rejection.
In addition, unlike the other devices existing at the time, this device is implanted empty to allow vascularization around the device and avoid cellular hypoxia. After 6 weeks, the insulin-secreting cells are injected through the injection ports.
Séverine and her team perform in vitro and in vivo studies on device design and Permeability (electromagnetism)|permeability, biointegration, function in diabetic rats, and immunization. They prove that their device is functional under conditions comparable to future Clinical trial|clinical trials demonstrating its safety and biocompatibility.
== Awards ==
Year	Award 	Category 	Result
2010	National competition to help create innovative companies	Emergency 	Winner
2011	National competition to help create innovative companies	Creation and development 	Winner
2012	Women's Gold Trophy 	Golden woman of innovation 	Winner
2013	Lady of the Legion of Honor 	 	Winner
2014	Irène-Joliot-Curie Award for her research at the CEED 	Trajectory of an enterprising woman	Winner
2018	Woman innovator in EU 	 	Finalist
Category:Biochemists
Category:Cell biologists