smiling

Cardiovascular disease (CVD) accounts for nearly one-third of all deaths worldwide. Coronary heart disease, obstructive arterial disease of the lower limbs and cerebrovascular disease are the main causes. Among the treatments proposed, vascular bypass surgery remains the most effective treatment for a long-term revascularization and which is done with an autologous vessel isolated from the patient if its vascular state allows this procedure. However, autologous vessels isolation implies invasive procedures and involves a longer recovery period. The synthetic vascular prostheses proposed on the market are not suitable for the replacement of small-diameter vessels because they induce many complications such as thrombosis probably due to low/no functionalization of their internal surface that is in direct contact with the blood. In both cases, vascular tissue engineering (VTI) could address the limitations of vascular grafts and offer potential therapeutic alternatives. The VTI brings together different processes with the objective of creating a cellularized substitute with biological and mechanical characteristics similar to those of native vessels. However, the biomaterials chosen, their coating and the cells used to functionalize them as well as the techniques used to combine these three factors remain major issues for the construction of small-diameter vascular grafts. Currently, the VTI tends to use natural materials, but rarely of human origin, hardly colonized by cells, which explains their poor performance. We have developed a natural, innovative vascular graft, which all components are derived from a single source: the human umbilical cord, which became today a valuable product for regenerative medicine. The “SMILING” project proposes the construction of a vascular graft from the matrix of a decellularized umbilical artery covered with a thin layer of extracellular matrix derived from the Wharton’s jelly, then colonized by mesenchymal cells isolated from Wharton's jelly. The very interesting results obtained in vitro, but also in vivo in a carotid bypass model in rabbits showed the real capacities and performance of this vascular graft by responding to native vessel specifications over a period of 3 weeks. These promising results require a validation, for clinical trials, in the large animal model with a graft prepared under conditions complying with Good Manufacturing Practices (GMP) for advanced therapy medicinal products (ATMP), to which this graft belongs. The relevance and success of this project relies on a complementary consortium of cardiovascular biologist and surgeons and is supported by an ATMP platform. The objectives of this project are: 1) production of the GMP grade SMILING graft 2) validation of its hemodynamic performance in different conditions, including stress tests, in a coronary artery bypass situation in pigs and 3) extending the duration of the post implantation follow-up to one year to ensure its long-term efficacy. By developing this non-immunogenic graft, completely of human origin, we propose an allogeneic “off-the-shelf” solution for clinical use allowing easier new approaches for myocardial and lower limbs revascularization, paediatric vascular diseases,and also as arteriovenous bridges for haemodialysis. Furthermore, our graft could supply a tissue bank of readily available vascular grafts ideal e for implantations by minimally invasive robotic surgeries having beneficial economic and societal benefits in terms of hospital stay and on patient recovery period.