Xenogeneic mesenchymal stem cell biocurative improves skin wounds healing in diabetic mice by increasing mast cells and the regenerative profile

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Manso, Gabriel Martins da Costa ; Elias-Oliveira, Jefferson ; Guimaraes, Jhefferson Barbosa ; Pereira, Italo Sousa ; Rodrigues, Vanessa Fernandes ; Burger, Beatriz ; Fantacini, Daianne Maciely Carvalho ; de Souza, Lucas Eduardo Botelho ; Rodrigues, Hosana Gomes ; Bonato, Vania Luiza Deperon ; Silva, Joao Santana ; Ramos, Simone Gusmao ; Tostes, Rita Cassia ; Manfiolli, Adriana Oliveira ; Caliari-Oliveira, Carolina ; Carlos, Daniela

• Document type: Journal article
• Source: REGENERATIVE THERAPY; v. 22, p. 11-pg., 2023-01-09.

Abstract

Introduction: Diabetes mellitus (DM) is a chronic disease and a major cause of mortality and morbidity worldwide. The hyperglycemia caused by DM induces micro and macrovascular complications that lead, among other consequences, to chronic wounds and amputations. Cell therapy and tissue engineering constitute recent therapeutic alternatives to improve wound healing in diabetic patients. The current study aimed to analyze the effectiveness of biocuratives containing human mesenchymal stem cells (MSCs) associated with a hydrogel matrix in the wound healing process and related inflammatory cell profile in diabetic mice. Methods: Biocuratives containing MSCs were constructed by 3D bioprinting, and applied to skin wounds on the back of streptozotocin (STZ)-induced type 1 diabetic (T1D) mice. The healing process, after the application of biocuratives with or without MSCs was histologically analyzed. In parallel, genes related to growth factors, mast cells (MC), M1 and M2 macrophage profiles were evaluated by RT-PCR. Macro-phages were characterized by flow cytometry, and MC by toluidine blue staining and flow cytometry. Results: Mice with T1D exhibited fewer skin MC and delayed wound healing when compared to the non -diabetic group. Treatment with the biocuratives containing MSCs accelerated wound healing and improved skin collagen deposition in diabetic mice. Increased TGF-b gene expression and M2 macrophage-related markers were also detected in skin of diabetic mice that received MSCs-containing biocuratives. Finally, MSCs upregulated IL-33 gene expression and augmented the number of MC in the skin of diabetic mice.Conclusion: These results reveal the therapeutic potential of biocuratives containing MSCs in the healing of skin wounds in diabetic mice, providing a scientific base for future treatments in diabetic patients.(c) 2023, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/). (AU)

• FAPESP's process: 19/22013-3 - Evaluation of the healing potential of mesenchymal cells biocuratives in hydrogel matrix for the treatment of induced skin ulcers in diabetic mice
• Grantee: Gabriel Martins da Costa Manso
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes
• Grantee: Daniela Carlos Sartori
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2