Research team
Expertise
My expertise lies in advanced therapies, specifically gene and cell therapies, aimed at treating cardiovascular diseases (CVDs) and musculoskeletal disorders (MSDs). I specialize in the molecular diagnosis of genetic disorders, including rare diseases (RD) and oncological conditions. My focus is on developing advanced therapy medicinal products (ATMPs) and substances of human origin (SoHO) for regenerative medicine, with an emphasis on innovative strategies that enhance patient outcomes through personalized treatment.
Genetically Engineered MSCs for Neovascular Modulation in Atherosclerosis.
Abstract
This research focuses on the critical role of pathological angiogenesis, driven by vascular endothelial growth factor (VEGF) gradients from adventitial vasa vasorum, in atherosclerotic plaque progression and instability. Fragile intraplaque neovessels, characterized by discontinuous basement membranes and low junction density, result in intraplaque hemorrhage, rendering the plaque more vulnerable. The study proposes an ex vivo gene therapy using mesenchymal stem cells (MSCs) engineered to overexpress sFLT1, a soluble VEGF receptor, to inhibit abnormal angiogenesis, stabilize plaques, and reduce rupture risk. By blocking VEGF-driven angiogenesis with sFLT1, this approach prevents the formation of fragile intraplaque neovessels. MSCs, with their ability to home to injury sites and regenerative potential, serve as optimal carriers for gene therapy and provide a promising solution to treat atherosclerosis. We will use an appropriate model, the ApoE-/-Fbn1C1039G/+ mice, which exhibit advanced atherosclerotic plaques with intraplaque neovascularization, hemorrhage and plaque rupture. Given the global rise in cardiovascular disease and the need for novel therapeutic solutions, this research seeks to fill an important gap. Genetically engineered MSCs have transformative potential in preventing atherosclerotic plaque progression and rupture through their local action. Key innovations include: (1) targeted therapy, in which MSCs expressing sFLT1 precisely target diseased tissues; (2) local action, in which engineered MSCs act directly on damage sites, improving efficacy and minimizing systemic effects; (3) enhanced regenerative potential, through genetic modifications that improve tissue repair, fibrosis reduction and immune modulation; and (4) versatility, extending this approach to treat autoimmune diseases and cancer in addition to cardiovascular disease.Researcher(s)
- Promoter: De Meyer Guido
- Fellow: Martin Leonardo
Research team(s)
Project type(s)
- Research Project