Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many prope...Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many properties with substantial therapeutic potential.Exosomes are particularly appealing for stroke therapy because of their low immunogenicity,effective cargo transport,and ability to cross the blood–brain barrier.Their diverse effects include neuroprotection,angiogenesis stimulation,inflammatory response modulation,and cell death pathway attenuation,synergistically promoting neuronal survival,tissue regeneration,and functional recovery.Exosomes also show potential as diagnostic indicators for early stroke identification and customized treatment options.Despite these promising qualities,current exosome-based therapeutics have some limitations.The heterogeneity of exosome release among cell types,difficulty in standardization and isolation techniques,and complications linked to dosage and targeted administration necessitates extensive investigation.It is critical to thoroughly understand exosomal processes and their complicated interactions within the cellular milieu.To improve the practicality and efficacy of exosome-based medicines,research efforts must focus on improving production processes,developing robust evaluation criteria,and developing large-scale isolation techniques.Altogether,exosomes’multifunctional properties offer a new route for transforming stroke treatment and significantly improving patient outcomes.展开更多
Objective:Intracerebral delivery of agents in liquid form is usually achieved through commercially available and durable metal needles.However,their size and texture may contribute to mechanical brain damage.Glass pip...Objective:Intracerebral delivery of agents in liquid form is usually achieved through commercially available and durable metal needles.However,their size and texture may contribute to mechanical brain damage.Glass pipettes with a thin tip may significantly reduce injection-associated brain damage but require access to prohibitively expensive programmable pipette pullers.This study is to remove the economic barrier to the application of minimally invasive delivery of therapeutics to the brain,such as chemical compounds,viral vectors,and cells.Methods:We took advantage of the rapid development of free educational online resources and emerging low-cost 3D printers by designing an affordable pipette puller(APP)to remove the cost obstacle.Results:We showed that our APP could produce glass pipettes with a sharp tip opening down to 20μm or less,which is sufficiently thin for the delivery of therapeutics into the brain.A pipeline from pipette pulling to brain injection using low-cost and open-source equipment was established to facilitate the application of the APP.Conclusion:In the spirit of frugal science,our device may democratize glass pipette-puling and substantially promote the application of minimally invasive and precisely controlled delivery of therapeutics to the brain for finding more effective therapies of brain diseases.展开更多
基金National Institutes of Health,Grant/Award Number:NIH R21NS133531。
文摘Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many properties with substantial therapeutic potential.Exosomes are particularly appealing for stroke therapy because of their low immunogenicity,effective cargo transport,and ability to cross the blood–brain barrier.Their diverse effects include neuroprotection,angiogenesis stimulation,inflammatory response modulation,and cell death pathway attenuation,synergistically promoting neuronal survival,tissue regeneration,and functional recovery.Exosomes also show potential as diagnostic indicators for early stroke identification and customized treatment options.Despite these promising qualities,current exosome-based therapeutics have some limitations.The heterogeneity of exosome release among cell types,difficulty in standardization and isolation techniques,and complications linked to dosage and targeted administration necessitates extensive investigation.It is critical to thoroughly understand exosomal processes and their complicated interactions within the cellular milieu.To improve the practicality and efficacy of exosome-based medicines,research efforts must focus on improving production processes,developing robust evaluation criteria,and developing large-scale isolation techniques.Altogether,exosomes’multifunctional properties offer a new route for transforming stroke treatment and significantly improving patient outcomes.
基金UMGCCC American Cancer Society Institutional Research,Grant/Award Numbers:IRG-18-160-16,NIH1R21AG077631-01,R03NS123733Maryland Stem Cell Research Fund,Grant/Award Numbers:2022-MSCRFL-5893,R03NS128459。
文摘Objective:Intracerebral delivery of agents in liquid form is usually achieved through commercially available and durable metal needles.However,their size and texture may contribute to mechanical brain damage.Glass pipettes with a thin tip may significantly reduce injection-associated brain damage but require access to prohibitively expensive programmable pipette pullers.This study is to remove the economic barrier to the application of minimally invasive delivery of therapeutics to the brain,such as chemical compounds,viral vectors,and cells.Methods:We took advantage of the rapid development of free educational online resources and emerging low-cost 3D printers by designing an affordable pipette puller(APP)to remove the cost obstacle.Results:We showed that our APP could produce glass pipettes with a sharp tip opening down to 20μm or less,which is sufficiently thin for the delivery of therapeutics into the brain.A pipeline from pipette pulling to brain injection using low-cost and open-source equipment was established to facilitate the application of the APP.Conclusion:In the spirit of frugal science,our device may democratize glass pipette-puling and substantially promote the application of minimally invasive and precisely controlled delivery of therapeutics to the brain for finding more effective therapies of brain diseases.