The use of exosomes derived from mesenchymal cells in the regenerative medicine: utilization of by-products of the cell therapy for the formulation of topical use compound for wounds healing

Abstract

Since the skin performs essential functions to the body, the loss of its integrity as observed in complex ulcers results in a number of complications. Basic pathologies such as diabetes are commonly related to the development of chronic ulcers. These ulcers, as well as other serious skin lesions such as those caused by extensive burns, are associated with poor prognosis, long treatment periods and high costs for health systems. Several therapeutic alternatives are available, but there is a range of patients refractory to conventional therapies. In this context, regenerative medicine through cell therapy has emerged in recent years as an alternative treatment for these patients. Among the cells used therapeutically, the mesenchymal stem cells (MSCs) stand out mainly for their immunomodulatory and regenerative properties. Much of the therapeutic potential of these cells has been attributed to the secretion of bioactive molecules in their extracellular microvesicles (MVs), especially the exosomes. In a first approach, the In Situ Cell Therapy developed a 3D biocurative containing mesenchymal cells for the treatment of patients with complex ulcers. However, knowing the therapeutic potential of MVs and aiming not only to obtain a more accessible shelf product, but also a product capable of providing continuity of treatment and the possibility of treating less complex lesions, the present project aims to isolate and characterize exosomes derived from MSCs, as well as to test the association of them to vehicles for the manufacture of topical products for the treatment of skin lesions. Thus, the exosomes, which contains a precious variety of microRNAs, growth factors and other proteins capable of assisting the healing process, will be isolated from the culture medium used during the expansion of MSCs in vitro. We will initially work with two forms for the use of the exosomes: 1) association of the exosomes with a pharmaceutical formulation for topical application; 2) use of the exosomes to enhance the effect of the biocuratives produced by three-dimensional (3D) bioprinting. Both products will be used for application in skin lesions. The development of cell therapy products using innovative techniques and according to good manufacturing practices is crucial for this type of treatment to be offered safely, non-invasively and effectively. In addition, the valuation of products of national technology will favor access to patients of the Unified Health System, since the importation of advanced therapy products is extremely expensive. In this way, by reaching the goals proposed in this project, and continuing with the pre-clinical and clinical tests in a second phase, we will bring to market innovative and affordable options for the treatment of these lesions. (AU)