The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
Antonello Petrella - One of the best experts on this subject based on the ideXlab platform.
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Mesoglycan induces the secretion of microvesicles by keratinocytes able to activate human fibroblasts and endothelial cells a novel mechanism in skin wound healing
European Journal of Pharmacology, 2020Co-Authors: Raffaella Belvedere, Emanuela Pessolano, Amalia Porta, Alessandra Tosco, Luca Parente, Francesco Petrella, Mauro Perretti, Antonello PetrellaAbstract:Mesoglycan is a fibrinolytic compound but recently promising pro-healing effects in skin wound repair have been reported. Previously, we have showed that Mesoglycan activates human keratinocytes, fibroblasts and endothelial cells and induces the secretion of microvesicles (EVs), particularly exosomes, from keratinocytes. These EVs may contribute to wound healing since they further activate cells generating an autocrine loop with a positive feedback. In this work, EVs isolated from keratinocytes, treated with Mesoglycan, have been tested on human fibroblasts and endothelial cells. The in vitro investigation has been carried out through Wound-Healing/invasion assays to analyze cell motility and assess the differentiation process. Then, the formation of capillary-like structures by human endothelial cells has been performed to evaluate in vitro angiogenesis. We found that EVs secreted from keratinocytes treated with Mesoglycan promote fibroblasts and endothelial cells migration and invasion. Furthermore, these receiving cells acquire a mesenchymal phenotype. Additionally, the angiogenesis appears strongly enhanced in presence of this kind of EVs. In conclusion, we show that EVs deriving from keratinocytes trigger a paracrine positive feedback able to further amplify the effects of Mesoglycan. This mechanism adds up to the autocrine loop previously reported and culminates with the activation of fibroblasts and endothelial cells. Particularly, this activation is amplified by the action of growth factors as FGF-2 (Fibroblast Growth Factor-2) for the fibroblasts and by VEGF (Vascular Endothelial Growth Factor) for the endothelial cells.
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The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing
MDPI AG, 2017Co-Authors: Raffaella Belvedere, Luca Parente, Francesco Petrella, Valentina Bizzarro, Antonello PetrellaAbstract:Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with Mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the Mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that Mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses
Raffaella Belvedere - One of the best experts on this subject based on the ideXlab platform.
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Mesoglycan induces the secretion of microvesicles by keratinocytes able to activate human fibroblasts and endothelial cells a novel mechanism in skin wound healing
European Journal of Pharmacology, 2020Co-Authors: Raffaella Belvedere, Emanuela Pessolano, Amalia Porta, Alessandra Tosco, Luca Parente, Francesco Petrella, Mauro Perretti, Antonello PetrellaAbstract:Mesoglycan is a fibrinolytic compound but recently promising pro-healing effects in skin wound repair have been reported. Previously, we have showed that Mesoglycan activates human keratinocytes, fibroblasts and endothelial cells and induces the secretion of microvesicles (EVs), particularly exosomes, from keratinocytes. These EVs may contribute to wound healing since they further activate cells generating an autocrine loop with a positive feedback. In this work, EVs isolated from keratinocytes, treated with Mesoglycan, have been tested on human fibroblasts and endothelial cells. The in vitro investigation has been carried out through Wound-Healing/invasion assays to analyze cell motility and assess the differentiation process. Then, the formation of capillary-like structures by human endothelial cells has been performed to evaluate in vitro angiogenesis. We found that EVs secreted from keratinocytes treated with Mesoglycan promote fibroblasts and endothelial cells migration and invasion. Furthermore, these receiving cells acquire a mesenchymal phenotype. Additionally, the angiogenesis appears strongly enhanced in presence of this kind of EVs. In conclusion, we show that EVs deriving from keratinocytes trigger a paracrine positive feedback able to further amplify the effects of Mesoglycan. This mechanism adds up to the autocrine loop previously reported and culminates with the activation of fibroblasts and endothelial cells. Particularly, this activation is amplified by the action of growth factors as FGF-2 (Fibroblast Growth Factor-2) for the fibroblasts and by VEGF (Vascular Endothelial Growth Factor) for the endothelial cells.
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The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing
MDPI AG, 2017Co-Authors: Raffaella Belvedere, Luca Parente, Francesco Petrella, Valentina Bizzarro, Antonello PetrellaAbstract:Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with Mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the Mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that Mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses
Petrella Antonello - One of the best experts on this subject based on the ideXlab platform.
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Supercritical impregnation of Mesoglycan into calcium alginate aerogel for wound healing
'Elsevier BV', 2020Co-Authors: Franco Paola, Pessolano Emanuela, Belvedere Raffaella, Petrella Antonello, De Marco IolandaAbstract:Mesoglycan (MSG) was impregnated onto calcium alginate aerogel (CAA) to produce an innovative topical device to be applied on wounds. The main purpose of the composite material is to favor the re‐epithelialization through a direct and immediate action, also offering a protective barrier to ensure a favorable and sterilized environment for the wound healing process. Impregnation kinetics and isotherms were determined at 18 MPa and 40 and 60 °C. Composite systems were analyzed using Field Emission Scanning Electron Microscopy (FESEM), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Fourier Transform Infrared (FT-IR) and UV–vis spectroscopies. A functional assay of in vitro wound healing confirmed the pro-migratory role of the composite system MSG/CAA, since an increase of the migration rate on fibroblast (BJ) cells and of the covered distance for keratinocytes (HaCaT) was observed with MSG impregnated on CAA compared to non-treated cells, CAA and pure MSG
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PCL/Mesoglycan Devices Obtained by Supercritical Foaming and Impregnation
'MDPI AG', 2019Co-Authors: Franco Paola, Pessolano Emanuela, Belvedere Raffaella, Petrella Antonello, Liparoti Sara, Pantani Roberto, De Marco IolandaAbstract:In this work, a one-shot process for the simultaneous foaming of polycaprolactone (PCL) and impregnation of Mesoglycan (MSG) into the porous structure was successfully attempted. Supercritical carbon dioxide plays the role of the foaming agent with respect to PCL and of the solvent with respect to MSG. The main objective is to produce an innovative topical device for application on skin lesions, promoting prolonged pro-resolving effects. The obtained device offers a protective barrier to ensure a favorable and sterilized environment for the wound healing process. The impregnation kinetics revealed that a pressure of 17 MPa, a temperature of 35 °C, and a time of impregnation of 24 h assured a proper foaming of PCL in addition to the impregnation of the maximum amount of MSG; i.e., 0.22 mgMSG/mgPCL. After a preliminary study conducted on PCL granules used as brought, the MSG impregnation was performed at the optimized process conditions also on a PCL film, produced by compression molding, with the final goal of producing medical patches. Comparing the dissolution profiles in phosphate buffered saline solution (PBS) of pure MSG and MSG impregnated on foamed PCL, it was demonstrated that the release of MSG was significantly prolonged up to 70 times. Next, we performed functional assays of in vitro wound healing, cell invasion, and angiogenesis to evaluate the biological effects of the PCL-derived MSG. Interestingly, we found the ability of this composite system to promote the activation of human keratinocytes, fibroblasts, and endothelial cells, as the main actors of tissue regeneration, confirming what we previously showed for the MSG alon
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Mesoglycan induces keratinocyte activation by triggering syndecan‐4 pathway and the formation of the annexin A1/S100A11 complex
'Wiley', 2019Co-Authors: Bizzarro Valentina, Pessolano Emanuela, Belvedere Raffaella, Petrella Francesco, Parente Luca, Perretti Mauro, Petrella AntonelloAbstract:Wound healing is a dynamic process comprising multiple events, such as inflammation, re‐epithelialization, and tissue remodeling. Re‐epithelialization phase is characterized by the engagement of several cell populations, mainly of keratinocytes that sequentially go through cycles of migration, proliferation, and differentiation to restore skin functions. Troubles can arise during the re‐epithelialization phase of skin wound healing particularly in keratinocyte migration, resulting in chronic non‐healing lesions, which represent a serious clinical problem. Over the last decades, the efforts aimed to find new pharmacological approaches for wound care were made, yet almost all current therapeutic strategies used remain inadequate or even ineffective. As such, it is crucial to identify new drugs that can enable a proper regeneration of the epithelium in wounded skin. Here, we have investigated the effects of the fibrinolytic drug Mesoglycan, a glycosaminoglycans mixture derived from porcine intestinal mucosa on HaCaT human keratinocytes that were used as in vitro experimental model of skin re‐epithelialization. We found that Mesoglycan induces keratinocyte migration and early differentiation by triggering the syndecan‐4/PKCα pathway and that these effects were at least in part, because of the formation of the annexin A1/S100A11 complex. Our data suggest that Mesoglycan may be useful as a new prohealing drug for skin wound care
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Effects of Prisma® Skin dermal regeneration device containing glycosaminoglycans on human keratinocytes and fibroblasts
'Informa UK Limited', 2018Co-Authors: Belvedere Raffaella, Bizzarro Valentina, Petrella Francesco, Parente Luca, Petrella AntonelloAbstract:Prisma® Skin is a new pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. It includes alginates, hyaluronic acid and mainly Mesoglycan. The latter is a natural glycosaminoglycan preparation containing chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin and it is used in the treatment of vascular disease. Glycosaminoglycans may contribute to the re-epithelialization in the skin wound healing, as components of the extracellular matrix. Here we describe, for the first time, the effects of Prisma® Skin in in vitro cultures of adult epidermal keratinocytes and dermal fibroblasts. Once confirmed the lack of cytotoxicity by Mesoglycan and Prisma® Skin, we have shown the increase of S and G2 phases of fibroblasts cell cycle distribution. We further report the strong induction of cell migration rate and invasion capability on both cell lines, two key processes of wound repair. In support of these results, we found significant cytoskeletal reorganization, following the treatments with Mesoglycan and Prisma® Skin, as confirmed by the formation of F-actin stress fibers. Additionally, together with a significant reduction of E-cadherin, keratinocytes showed an increase of CD44 expression and the translocation of ezrin to the plasma membrane, suggesting the involvement of CD44/ERM (ezrin-radixin-moesin) pathway in the induction of the analyzed processes. Furthermore, as showed by immunofluorescence assay, fibroblasts treated with Mesoglycan and Prisma® Skin exhibited the increase of Fibroblast Activated Protein α and a remarkable change in shape and orientation, two common features of reactive stromal fibroblasts. In all experiments Prisma® Skin was slightly more potent than Mesoglycan. In conclusion, based on these findings we suggest that Prisma® Skin may be able to accelerate the healing process in venous skin ulcers, principally enhancing re-epithelialization and granulation processes
Luca Parente - One of the best experts on this subject based on the ideXlab platform.
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Mesoglycan induces the secretion of microvesicles by keratinocytes able to activate human fibroblasts and endothelial cells a novel mechanism in skin wound healing
European Journal of Pharmacology, 2020Co-Authors: Raffaella Belvedere, Emanuela Pessolano, Amalia Porta, Alessandra Tosco, Luca Parente, Francesco Petrella, Mauro Perretti, Antonello PetrellaAbstract:Mesoglycan is a fibrinolytic compound but recently promising pro-healing effects in skin wound repair have been reported. Previously, we have showed that Mesoglycan activates human keratinocytes, fibroblasts and endothelial cells and induces the secretion of microvesicles (EVs), particularly exosomes, from keratinocytes. These EVs may contribute to wound healing since they further activate cells generating an autocrine loop with a positive feedback. In this work, EVs isolated from keratinocytes, treated with Mesoglycan, have been tested on human fibroblasts and endothelial cells. The in vitro investigation has been carried out through Wound-Healing/invasion assays to analyze cell motility and assess the differentiation process. Then, the formation of capillary-like structures by human endothelial cells has been performed to evaluate in vitro angiogenesis. We found that EVs secreted from keratinocytes treated with Mesoglycan promote fibroblasts and endothelial cells migration and invasion. Furthermore, these receiving cells acquire a mesenchymal phenotype. Additionally, the angiogenesis appears strongly enhanced in presence of this kind of EVs. In conclusion, we show that EVs deriving from keratinocytes trigger a paracrine positive feedback able to further amplify the effects of Mesoglycan. This mechanism adds up to the autocrine loop previously reported and culminates with the activation of fibroblasts and endothelial cells. Particularly, this activation is amplified by the action of growth factors as FGF-2 (Fibroblast Growth Factor-2) for the fibroblasts and by VEGF (Vascular Endothelial Growth Factor) for the endothelial cells.
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The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing
MDPI AG, 2017Co-Authors: Raffaella Belvedere, Luca Parente, Francesco Petrella, Valentina Bizzarro, Antonello PetrellaAbstract:Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with Mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the Mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that Mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses
Francesco Petrella - One of the best experts on this subject based on the ideXlab platform.
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Mesoglycan induces the secretion of microvesicles by keratinocytes able to activate human fibroblasts and endothelial cells a novel mechanism in skin wound healing
European Journal of Pharmacology, 2020Co-Authors: Raffaella Belvedere, Emanuela Pessolano, Amalia Porta, Alessandra Tosco, Luca Parente, Francesco Petrella, Mauro Perretti, Antonello PetrellaAbstract:Mesoglycan is a fibrinolytic compound but recently promising pro-healing effects in skin wound repair have been reported. Previously, we have showed that Mesoglycan activates human keratinocytes, fibroblasts and endothelial cells and induces the secretion of microvesicles (EVs), particularly exosomes, from keratinocytes. These EVs may contribute to wound healing since they further activate cells generating an autocrine loop with a positive feedback. In this work, EVs isolated from keratinocytes, treated with Mesoglycan, have been tested on human fibroblasts and endothelial cells. The in vitro investigation has been carried out through Wound-Healing/invasion assays to analyze cell motility and assess the differentiation process. Then, the formation of capillary-like structures by human endothelial cells has been performed to evaluate in vitro angiogenesis. We found that EVs secreted from keratinocytes treated with Mesoglycan promote fibroblasts and endothelial cells migration and invasion. Furthermore, these receiving cells acquire a mesenchymal phenotype. Additionally, the angiogenesis appears strongly enhanced in presence of this kind of EVs. In conclusion, we show that EVs deriving from keratinocytes trigger a paracrine positive feedback able to further amplify the effects of Mesoglycan. This mechanism adds up to the autocrine loop previously reported and culminates with the activation of fibroblasts and endothelial cells. Particularly, this activation is amplified by the action of growth factors as FGF-2 (Fibroblast Growth Factor-2) for the fibroblasts and by VEGF (Vascular Endothelial Growth Factor) for the endothelial cells.
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The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing
MDPI AG, 2017Co-Authors: Raffaella Belvedere, Luca Parente, Francesco Petrella, Valentina Bizzarro, Antonello PetrellaAbstract:Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with Mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the Mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that Mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses