Exogenous peripheral blood mononuclear cells affect the healing process of deep-degree burns

Abstract

The regenerative repair of deep-degree (second degree) burned skin remains a notable challenge in the treatment of burn injury, despite improvements being made with regards to treatment modality and the emergence of novel therapies. Fetal skin constitutes an attractive target for investigating scarless healing of burned skin. To investigate the inflammatory response during scarless healing of burned fetal skin, the present study developed a nude mouse model, which was implanted with normal human fetal skin and burned fetal skin. Subsequently, human peripheral blood mononuclear cells (PBMCs) were used to treat the nude mouse model carrying the burned fetal skin. The expression levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were investigated during this process. In the present study, fetal skin was subcutaneously implanted into the nude mice to establish the murine model. Hematoxylin and eosin staining was used to detect alterations in the skin during the development of fetal skin and during the healing process of deep-degree burned fetal skin. The expression levels of MMP-9 and TIMP-1 were determined using immunochemical staining, and their staining intensity was evaluated by mean optical density. The results demonstrated that fetal skin subcutaneously implanted into the dorsal skin flap of nude mice developed similarly to the normal growth process in the womb. In addition, the scarless healing process was clearly observed in the mice carrying the burned fetal skin. A total of 2 weeks was required to complete scarless healing. Following treatment with PBMCs, the burned fetal skin generated inflammatory factors and enhanced the inflammatory response, which consequently resulted in a reduction in the speed of healing and in the formation of scars. Therefore, exogenous PBMCs may alter the lowered immune response environment, which is required for scarless healing, resulting in scar formation. In conclusion, the present study indicated that the involvement of inflammatory cells is important during the healing process of deep-degree burned skin, and MMP-9 and TIMP-1 may serve important roles in the process of scar formation.

Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor, a candidate mediator of cochlear regeneration mechanisms

“…TIMP1 is an inhibitor of MMP9 and the balance between them is a key regulator of the signaling network in the injured nerve 42 . The significance of MMP9/TIMP1 balance is not well understood, but it was also demonstrated to regulate healing process of burned fetal skin 65 . An increased MMP9/TIMP1 ratio promotes the degradation of extracellular matrix (ECM) to allow cellular migration, while a reduced MMP9/TIMP1 ratio drives reconstruction of the ECM during healing process 65 .…”

“…The significance of MMP9/TIMP1 balance is not well understood, but it was also demonstrated to regulate healing process of burned fetal skin 65 . An increased MMP9/TIMP1 ratio promotes the degradation of extracellular matrix (ECM) to allow cellular migration, while a reduced MMP9/TIMP1 ratio drives reconstruction of the ECM during healing process 65 . TIMP1 may also act as cytokine independently of MMP9 inhibition to promote cell survival and proliferation 66 .…”

Clinical significance of serum matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the first phase of burn trauma evolution

“…None of the patients enrolled in the study had septic complications, but our case series included patients in a good health state and without a history of major non-communicable diseases, such as diabetes, which could influence the evolution of the burns (21). Although most studies have investigated MMP-9 or TIMP-1 immunohistochemical reactivity (4,22), we decided to measure the serum level of biomarkers. Our decision was based on the following arguments: i) MMP-9, or TIMP-1 immunohistochemical reactivity may not correspond to in vivo enzymatic activity (12); ii) the study group was compared with the control group of healthy volunteers, without thermal injury.…”

“…In early inflammation, increased levels of proinflammatory cytokines bring neutrophils and monocytes to the site (3). Further, proteolytic enzymes, such as matrix metalloproteinases (MMPs), are released from neutrophils (4). MMPs are the main class of enzymes responsible for the degradation or resorption of all extracellular matrix (ECM) components (5,6).…”

Analysis of peripheral blood lymphocytes in burns of varying degrees in the assessment of immune suppression

“…(2), and Guanying YY et al (5) suggest that T cell immunosuppression is associated with decreased production of IL-2, a cytokine that is primarily produced by peripheral blood mononuclear cells and Th1-Ly. Immunosuppression is also affected by increased production of IL-4 and IL-10, cytokines that reduce Th1-Ly function and redirect T lymphocyte differentiation in favor of Th2 lymphocyte subpopulation, andreducing Th1 lymphocyte phenotype.…”