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.

Improved Transplanted Stem Cell Survival in a Polymer Gel Supplemented with Tenascin C Accelerates Healing and Reduces Scarring of Murine Skin Wounds

“…Herein, we have shown that our polymer-based approach enhances the survival of these cells while retaining stem cell markers, resulting in a microenvironment projected towards a more regenerative healing. Compared to hydrogel and injection delivery systems, the PEG-collagen delivers the MSCs in a protective scaffold that biodegrades 17,21,22 over time to allow for a reduction in the otherwise robust and damaging immune influx, and increased angiogenesis with a subsequent improvement of healing.…”

Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization

“…Mesenchymal stem cell (MSC) is one of the most widely studied stem cells for wound healing, and several studies have demonstrated inspiring preclinical results through animal models [2–5]. Nonetheless, several arguments still exist against the widely use of MSC in clinics, including the probability of tumorigenesis and low cell production from MSC harvesting.…”

Alternative animal model for studies of total skin thickness burns

“…Several works using aluminum coupled to the soldering iron have been presented as an effective method for the reproduction of the experimental model of third degree burns 8,9,[16][17][18][19] , but there is a great discrepancy in the temperature used, which may vary from 100ºC to 200ºC, in addition to the time of application that varies between 5 to 30 seconds. Caliari-Oliveira et al…”

“…Brassolatti et al 18 presented a study in which the experimental model of third degree burn was carried out through an aluminum plate coupled to a soldering iron, but the temperature used was significantly lower, being 150ºC with application on the back of the animal for 10 seconds, demonstrating that it is not necessary to use very high temperatures to perform this type of injury. The literature also shows lower temperatures, 100°C 16,19 and 130°C, using the model with soldering iron for the reproduction of third degree burns, but several other studies have used these temperatures with different exposure times, in order to perform 20,21 , thus generating disagreement regarding the morphological results that characterize the involvement of the tissue thickness.…”