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Therapies to deep burn injuries remain a global challenge. Human amniotic membrane (hAM) is a biomaterial that has been increasingly explored by the field of regenerative medicine. A decellularized hAM (DhAM) can be used as scaffold for mesenchymal stromal cells (MSCs) to grow without the loss of their stemness potential, allowing its application as cell therapy for wound healing. In this work, we associated DhAM with adipose-derived mesenchymal stromal cells (DhAM+AD-MSC), as a therapy strategy for second-degree burns in a preclinical model . Animals with induced second-degree burns were divided into 4 groups: control, which consists of a non-adherent gauze; a synthetic commercial dressing as the positive control (control+); DhAM; and DhAM plus rat AD-MSCs (DhAM+AD-MSCs), followed by detailed and long term analysis (5 weeks). The macroscopical analysis showed the healing improvement in the wound area after the DhAM+AD-MSC treatment. Histological analysis also showed no alteration in the animal organs and a regular epithelial progression in comparison to the control. This observation was also confirmed by the analysis of suprabasal layers in the neoepidermis with CK10, showing a stratified and differentiated epithelium, when compared to Control and Control+. A strong CD73 (ecto-5′-nucleotidase) labeling was observed in the first two weeks postburn in dermis and epidermis. The expression in dermis was stronger in the second week in the middle of the wound, when comparing the Control+ with DhAM+AD-MSCs (p=0.0238). In the epidermis the expression of CD73 was increased in all regions when compared to the control. This data suggests the involvement of this protein on wound healing. A low CD11b labeling was observed in DhAM+AD-MSCs treatment group mainly in the last treatment week, in comparison to Control and Control+ (p<0.0001), which indicates a reduction in the inflammatory process. MSCs through CD73 can release high concentrations of adenosine, an immunosuppressive molecule, suggesting that this could be the mechanism by which the inflammation was better modulated in the DhAM+AD-MSCs group. The results obtained with this preclinical model confirm the effectiveness and safety of this low-cost and highly available dressing for future clinical application as a therapy for burn treatments.

Purinergic signaling is a necessary mechanism to trigger or even amplify cell communication. Its ligands, notably adenosine triphosphate (ATP) and adenosine, modulate specific membrane-bound receptors in virtually all human cells. Regardless of the stage of the pregnancy, cellular communication between maternal, placental, and fetal cells is the paramount mechanism to sustain its optimal status. In this review, we describe the crucial role of purinergic signaling on the regulation of the maternal-fetal trophic exchanges, immune control, and endocrine exchanges throughout pregnancy. The nature of the modulation of both ATP and adenosine on the embryo-maternal interface, going through placental invasion until birth delivery depends on the general maternal-fetal health state and consequently on the selective activation of their specific receptors. In addition, an increasing number of studies have been demonstrating the pivotal role of ATP and adenosine in modulating deleterious effects of suboptimal conditions of pregnancy. Here, we discuss the role of purinergic signaling on the balance that coordinates the embryomaternal exchanges and a promising therapeutic venue in the context of pregnancy disorders.