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Evaluation of the healing potential of mesenchymal cells biocuratives in hydrogel matrix for the treatment of induced skin ulcers in diabetic mice

Grant number: 19/22013-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Daniela Carlos Sartori
Grantee:Gabriel Martins da Costa Manso
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Diabetes mellitus (DM) is an endemic disease and one of the main causes of death worldwide. Hyperglycemia causes micro and macrovascular complications, and the consequences include, among others, chronic ulcers and amputations. Wound healing involves highly regulated and synchronized events and the vascular, proliferative and immune deficiencies of DM directly affect this process, leading to non-healing ulcers, or those that take a long time to heal. Current treatment for these ulcers is usually not effective, resulting in high rates of amputations, generalized infections, and mortality. Cell therapy and tissue engineering are some of the recent alternatives aimed to solve the cellular and molecular disorders of healing in diabetics. There are some studies using the application of cells involved in healing events, such as mesenchymal cells and fibroblasts, which are applied directly to the edges of ulcers or associated with matrices such as hydrogels. Thus, the objective of the present study will be to analyze the relevance of healing modulation in diabetic animals by mesenchymal cells associated with a hydrogel matrix. For this, hydrogel matrix biocuration containing mesenchymal cells will be made by 3D bioprinting and supplied by startup In Situ - Cell Therapy, they will be applied to experimental ulcers in streptozotocin-induced diabetic mice. The healing process of ulcers treated or not with biocuration containing mesenchymal cells will be histologically evaluated in diabetic and non-diabetic mice. In parallel, the quantification of pro-fibrotic, angiogenic and inflammatory factors (local and systemic) and the quantification of gene expression associated with classical macrophage activation (M1 - pro-inflammatory) and alternative activation (M2 - anti-inflammatory) phenotypes will be performed. The results of this research project may support the use of biocuration containing mesenchymal cells for the treatment of skin ulcers in diabetic patients.