The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulat...The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.展开更多
Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatm...Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.展开更多
BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and d...BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into展开更多
基金Supported by “Instituto de Salud Carlos III”(ISCIII)“Ministerio de Economía y Competitividad”(MINECO) and European Union (EU),No. PI18/01659 and No. PI21/01935
文摘The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.
文摘Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.
基金Supported by Government of Extremadura GAEDAF Research Group,No.GR18003Ministerio de Educación,Cultura y Deporte,No.FPU15/00452and Instituto de Salud Carlos III,No.PI15/01857 and No.PI18/01659.
文摘BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into
