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Título/Title/Titulo

INFLUENCE OF THE SOURCE OF MESENCHYMAL STEM CELLS FOR TISSUE ENGINEERING: DERMAL VERSUS ADIPOSE TISSUE IN SKIN WOUND HEALING

Introdução/Introduction/Introdución

The skin is constantly challenged by external factors and highly susceptible to traumas. When injured, cutaneous repair occurs by wound healing, a complex process comprising inflammation, proliferation and remodeling phases, which restores homeostasis but not tissue functionality. Large skin wounds such as burns lead to secondary disorders and death if not quickly stabilized. Thus, new strategies are necessary to accelerate wound closure and improve the healing quality. In this context, tissue engineering and cell therapies arise as promising alternatives. Mesenchymal stem cells (MSCs), found in virtually all adult tissues, are easy to obtain and have high proliferation capacity in vitro. Despite sharing stem cell characteristics such as self-renew, differentiation to mesodermal tissues and immunophenotype, MSCs from distinct niches can present individual features. Therefore, studying diverse sources of MSCs is important to develop future therapeutic approaches.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

This study aimed to compare MSCs from human abdominal dermis (DSC) and adipose tissue (ASC) in association with Integra™ matrix during the process of skin wound healing. DSC and ASC used in this study were previously isolated from human abdominoplasty skin samples and presented similar immunophenotypic expression of CD90+, CD73+, CD105+, CD34- and CD45- and mesodermal differentiation potential to adipocytes, osteocytes and chondrocytes. DSC and ASC were cultivated in Integra™ matrix and used as therapy to excisional skin wounds in mice C57bl6. Control groups received only the Integra™ without cells. Wounds were evaluated clinically and histologically after 3, 7, 21 and 60 days. Results showed a higher number of nucleated cells per field analyzed inside the matrix in DSC (81.17 ± 35.3 SD) and ASC (102.5 ± 31.75 SD) groups in comparison with the control (39.33 ± 15.9 SD) in the inflammatory phase of wound healing (day 3). Grafts were more pinkish, a clinical sign of integration, in DSC and ASC groups in comparison with the control during the proliferation phase (day 7). Accordingly, histological analysis showed a thicker granulation tissue and more blood vessels in cell-treated groups than the control group (angiogenesis: 0.58 ± 0.1 SD in DSC, 0.6 ± 0.1 SD in ASC and 0.33 ± 0.06 SD in control, per field). After 21 days, the wounds were significantly more closed in DSC (90.27% ± 18.78 SD) and ASC (86.88% ± 24.5 SD) groups than control (55.78% ± 29.06 SD). At both early (day 21) and late (day 60) remodeling phase, the neoepidermis was more similar to the normal epidermis and more skin appendices (as hair follicles and sebaceous glands) were present in cell-treated groups than the control. Besides, Integra™ degradation and collagen density was significantly higher and more similar to normal skin in DSC treated group than the control group. In late remodeling phase, DSC treated group presented a smaller scar and a higher score of elastic fibers than the control group. Together, these results suggest that the source of MSC influence in the clinical outcome, however, both DSC and ASC presented faster wound closure and better healing features than the control.

Considerações Finais/Final considerations/Consideraciones finales

In conclusion, association of both DSC and ASC to Integra™ represents promising therapeutic strategy to improve human cutaneous repair. Furthermore, the use of DSC results in better overall quality of healing than ASC.
This study was supported by CNPq, CAPES / PDSE, MCTIC and INCT-REGENERA.

Palavras-chave/Key words/Palabras clave

cutaneous repair, mesenchymal stromal cells, MSC, translational study, histology.