title: Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model.
abstract: Major skin burns are difficult to treat. Patients often require special care and long-term hospitalization. Besides specific complications associated with the wounds themselves, there may be impairment of the immune system and of other organs. Mesenchymal stromal cells (MSCs) are a recent therapeutic alternative to treat burns, mainly aiming to accelerate the healing process. Several MSC properties favor their use as therapeutic approach, as they promote angiogenesis, stimulate regeneration, and enhance the immunoregulatory function. Moreover, since patients with extensive burns require urgent treatment and because the expansion of autologous MSCs is a time-consuming process, in this present study we chose to evaluate the therapeutic potential of xenogeneic MSCs in the treatment of severe burns in rats. MSCs were isolated from mouse bone marrow, expanded in vitro, and intradermally injected in the periphery of burn wounds. MSC-treated rats presented higher survival rates (76.19%) than control animals treated with PBS (60.86%, p < 0.05). In addition, 60 days after the thermal injury, the MSC-treated group showed larger proportion of healed areas within the burn wounds (90.81 ± 5.05%) than the PBS-treated group (76.11 ± 3.46%, p = 0.03). We also observed that CD4(+) and CD8(+) T cells in spleens and in damaged skin, as well as the percentage of neutrophils in the burned area, were modulated by MSC treatment. Plasma cytokine (TGF-β, IL-10, IL-6, and CINC-1) levels were also altered in the MSC-treated rats, when compared to controls. Number of injected GFP(+) MSCs progressively decreased over time, and 60 days after injection, few MSCs were still detected in the skin of treated animals. This study demonstrates the therapeutic effectiveness of intradermal application of MSCs in a rat model of deep burns, providing basis for future regenerative therapies in patients suffering from deep burn injuries.
authors.affiliation: Department of Biochemistry and Immunology, Basic and Applied Immunology Program, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Caliari-Oliveira
authors.forename: Juliana Navarro Ueda
authors.initials: JN
authors.lastname: Yaochite
authors.forename: Leandra Náira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Patrícia Vianna Bonini
authors.initials: PV
authors.lastname: Palma
authors.forename: Daniela
authors.initials: D
authors.lastname: Carlos
authors.forename: Fernando de Queiróz
authors.initials: Fde Q
authors.lastname: Cunha
authors.forename: Daurea Abadia
authors.initials: DA
authors.lastname: De Souza
authors.forename: Marco Andrey Cipriani
authors.initials: MA
authors.lastname: Frade
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Kelen Cristina Ribeiro
authors.initials: KC
authors.lastname: Malmegrim
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Oliveira
authors.forename: Julio César
authors.initials: JC
authors.lastname: Voltarelli
mesh_terms: D000818:Animals; D002056:Burns / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology; D012867:Skin / Q000293:injuries; D014183:Transplantation, Heterologous / Q000379:methods; D014945:Wound Healing