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

• Tipo de documento: Artigo Científico
• Fonte: REGENERATIVE THERAPY; v. 22, p. 11-pg., 2023-01-09.

Resumo

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)

• Processo FAPESP: 19/22013-3 - Avaliação do potencial de cicatrização de biocurativos de células mesenquimais em matriz de hidrogel para o tratamento de úlceras cutâneas induzidas em camundongos diabéticos
• Beneficiário: Gabriel Martins da Costa Manso
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/14815-0 - Estudo do perfil do microbioma intestinal e do potencial terapêutico de estratégias de intervenção na imunopatogenia do Diabetes tipo 1 e 2
• Beneficiário: Daniela Carlos Sartori
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2