Cellular interconnectivity in regeneration: a pioneering strategy for healthy skin
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Presented by: Mélanie Mangier
Introduction
Regeneration was for a long time restricted to re-epithelialization depending on keratinocytes and dermal matrix restructuring carried out by fibroblasts. Recent scientific advances shed to light that regeneration is a more complex process requiring the intervention of cutaneous, vascular, and immune systems. Indeed, a population of pro-regenerating macrophages stimulates extracellular matrix remodeling, and the vascular network allows the supply to the skin of elements favoring its regeneration like nutrients, cells, and mediators. These three major biological systems are interconnected by the fibroblast, which orchestrates the stages of the regenerating process through the secretion of a specific pool of growth factors. This latter positively regulates the activity of keratinocytes, fibroblasts, endothelial and immune cells, for an optimal and global regenerating effect. To this date, evolutions of cutaneous, immune and vascular interconnectivity in regeneration in the course of aging is poorly described.
Aim of the study
The objective of this study was to evaluate modifications of the fibroblast regenerating complex and the consequences on cutaneous, immune and vascular systems in the course of aging.
Methods
Changes in fibroblast regenerating complex were studied through the analysis of the expression of EGF, IGF-1 and PDGFA by quantitative PCR and of the synthesis of TGF-b1, KGF, VEGF and FGF2 by ELISA assay. This study was completed by fibroblasts functionality analysis determined by the assessment of the migration of fibroblasts, their differentiation into myofibroblasts and their capacity to synthesize a collagen I network. These studies were conducted on the one hand on young human fibroblasts obtained from facial plasties and aged human fibroblasts obtained by successive replications.
The impact of the regenerating complex modifications with aging on key systems of skin regeneration was next evaluated by various biological assays. The capacity of migration of keratinocytes treated by secretome of aged fibroblasts was evaluated. The functionality of the immune system was determined by the study of the differentiation of macrophages derived from blood monocytes into pro-regenerating macrophages after treatment with the secretome of aged fibroblasts. Finally, the functionality of the vascular system was evaluated by the analysis of the migration and cohesion of young endothelial cells and aged cells obtained by successive replications, after treatment with the secretome of aged fibroblasts.
Results
Aging results in a significant depletion of growth factors of the fibroblast regenerating complex. Indeed, compared to young fibroblasts, aged fibroblasts exhibited a reduced capacity to express or synthesize KGF, EGF, IGF-1, FGF2, PDGFA, TGF-β1 and VEGF. Moreover, studies showed that aging has a harmful effect on the metabolism of fibroblasts since aged fibroblasts displayed a reduction in the capacities of migration, differentiation into myofibroblasts and synthesis of a collagen I network, compared to young fibroblasts.
Experiments also demonstrated that the depletion of growth factors of the regenerating complex, secreted by aged fibroblasts, significantly impedes interconnectivity between cutaneous, immune and vascular systems. Compared to young keratinocytes, the migration capacity of old keratinocytes treated with the secretome of aged fibroblasts was decreased. The exhaustion of the regenerating complex has also a negative impact on the pro-regenerating population of the immune system and on the vascular system. In response to treatment with the secretome of aged fibroblasts, macrophages differentiation into pro-regenerating macrophages was reduced and the migration and cohesion capacities of aged endothelial cells were impaired.
Discussion
This innovative modeling approach demonstrates for the first time that aging results in depletion of the fibroblast regenerating complex and that it has a significant impact on the interactions of fibroblasts with their environment. This work emphasizes the key role of this regenerative complex in maintaining interconnectivity and functionality of cutaneous, immune and vascular systems during regeneration process with aging.
Conclusion
Based on these discoveries, SILAB has developed a natural active ingredient composed of oligo-glucans from Saccharomyces cerevisiae that revitalizes the interconnectivity of the three biological systems by the endogenous production of a growth elixir able to reactivate the regeneration process for an anti-aging effect.
Regeneration was for a long time restricted to re-epithelialization depending on keratinocytes and dermal matrix restructuring carried out by fibroblasts. Recent scientific advances shed to light that regeneration is a more complex process requiring the intervention of cutaneous, vascular, and immune systems. Indeed, a population of pro-regenerating macrophages stimulates extracellular matrix remodeling, and the vascular network allows the supply to the skin of elements favoring its regeneration like nutrients, cells, and mediators. These three major biological systems are interconnected by the fibroblast, which orchestrates the stages of the regenerating process through the secretion of a specific pool of growth factors. This latter positively regulates the activity of keratinocytes, fibroblasts, endothelial and immune cells, for an optimal and global regenerating effect. To this date, evolutions of cutaneous, immune and vascular interconnectivity in regeneration in the course of aging is poorly described.
Aim of the study
The objective of this study was to evaluate modifications of the fibroblast regenerating complex and the consequences on cutaneous, immune and vascular systems in the course of aging.
Methods
Changes in fibroblast regenerating complex were studied through the analysis of the expression of EGF, IGF-1 and PDGFA by quantitative PCR and of the synthesis of TGF-b1, KGF, VEGF and FGF2 by ELISA assay. This study was completed by fibroblasts functionality analysis determined by the assessment of the migration of fibroblasts, their differentiation into myofibroblasts and their capacity to synthesize a collagen I network. These studies were conducted on the one hand on young human fibroblasts obtained from facial plasties and aged human fibroblasts obtained by successive replications.
The impact of the regenerating complex modifications with aging on key systems of skin regeneration was next evaluated by various biological assays. The capacity of migration of keratinocytes treated by secretome of aged fibroblasts was evaluated. The functionality of the immune system was determined by the study of the differentiation of macrophages derived from blood monocytes into pro-regenerating macrophages after treatment with the secretome of aged fibroblasts. Finally, the functionality of the vascular system was evaluated by the analysis of the migration and cohesion of young endothelial cells and aged cells obtained by successive replications, after treatment with the secretome of aged fibroblasts.
Results
Aging results in a significant depletion of growth factors of the fibroblast regenerating complex. Indeed, compared to young fibroblasts, aged fibroblasts exhibited a reduced capacity to express or synthesize KGF, EGF, IGF-1, FGF2, PDGFA, TGF-β1 and VEGF. Moreover, studies showed that aging has a harmful effect on the metabolism of fibroblasts since aged fibroblasts displayed a reduction in the capacities of migration, differentiation into myofibroblasts and synthesis of a collagen I network, compared to young fibroblasts.
Experiments also demonstrated that the depletion of growth factors of the regenerating complex, secreted by aged fibroblasts, significantly impedes interconnectivity between cutaneous, immune and vascular systems. Compared to young keratinocytes, the migration capacity of old keratinocytes treated with the secretome of aged fibroblasts was decreased. The exhaustion of the regenerating complex has also a negative impact on the pro-regenerating population of the immune system and on the vascular system. In response to treatment with the secretome of aged fibroblasts, macrophages differentiation into pro-regenerating macrophages was reduced and the migration and cohesion capacities of aged endothelial cells were impaired.
Discussion
This innovative modeling approach demonstrates for the first time that aging results in depletion of the fibroblast regenerating complex and that it has a significant impact on the interactions of fibroblasts with their environment. This work emphasizes the key role of this regenerative complex in maintaining interconnectivity and functionality of cutaneous, immune and vascular systems during regeneration process with aging.
Conclusion
Based on these discoveries, SILAB has developed a natural active ingredient composed of oligo-glucans from Saccharomyces cerevisiae that revitalizes the interconnectivity of the three biological systems by the endogenous production of a growth elixir able to reactivate the regeneration process for an anti-aging effect.