This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central ne...This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central nervous injury functional return depends on spinal cord nerve cell growth within the central nervous system. Basic science, clinical research and human application has demonstrated good and useful motor function after ventral root avulsion followed by spinal cord reimplantation. Recently, sensory return could be demonstrated following spinal cord surgery bypassing the injured primary sensory neuron. Experimental data showed that most of the recovery depended on new growth reinnervating peripheral receptors. Restored sensory function and the return of spinal reflex was demonstrated by electrophysiology and functional magnetic resonance imaging of human cortex. This spinal cord surgery is a unique treatment of central nervous system injury resulting in useful functional return. Further improvements will not depend on surgical improvements. Adjuvant therapy aiming at ameliorating the activity in retinoic acid elements in dorsal root ganglion neurons could be a new therapeutic avenue in restoring spinal cord circuits after nerve root avulsion injury.展开更多
Many cells possess the ability to engulf and incorporate particles by phagocytosis.This active process is characteristic of microorganisms as well as higher order species.In mammals,monocytes,macrophages,and microglia...Many cells possess the ability to engulf and incorporate particles by phagocytosis.This active process is characteristic of microorganisms as well as higher order species.In mammals,monocytes,macrophages,and microglia are among the so-called professional phagocytes.In addition,cells such as fibroblast and chondrocytes are classified as nonprofessional phagocytes.Professional phagocytes play important roles in both the innate and adaptive immune responses,wound healing,and tissue homeostasis.Consequently,these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases.Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation.Consequently,efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis.However,this approach carries significant technical challenges,particularly for protein cargos.We have focused on the development of nanoscale cocrystalline protein depots,known as PODS®,that contain protein cargos,including cytokines.Here,we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes,such as highly sustained release of cargo,that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery.Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response.Moreover,the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic cells.The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.展开更多
基金the Wellcome Trust,Karolinska Institutet,Swedish Defence(No.FOT-AF.9221006)Darwin Trust of Edinburgh
文摘This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central nervous injury functional return depends on spinal cord nerve cell growth within the central nervous system. Basic science, clinical research and human application has demonstrated good and useful motor function after ventral root avulsion followed by spinal cord reimplantation. Recently, sensory return could be demonstrated following spinal cord surgery bypassing the injured primary sensory neuron. Experimental data showed that most of the recovery depended on new growth reinnervating peripheral receptors. Restored sensory function and the return of spinal reflex was demonstrated by electrophysiology and functional magnetic resonance imaging of human cortex. This spinal cord surgery is a unique treatment of central nervous system injury resulting in useful functional return. Further improvements will not depend on surgical improvements. Adjuvant therapy aiming at ameliorating the activity in retinoic acid elements in dorsal root ganglion neurons could be a new therapeutic avenue in restoring spinal cord circuits after nerve root avulsion injury.
文摘Many cells possess the ability to engulf and incorporate particles by phagocytosis.This active process is characteristic of microorganisms as well as higher order species.In mammals,monocytes,macrophages,and microglia are among the so-called professional phagocytes.In addition,cells such as fibroblast and chondrocytes are classified as nonprofessional phagocytes.Professional phagocytes play important roles in both the innate and adaptive immune responses,wound healing,and tissue homeostasis.Consequently,these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases.Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation.Consequently,efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis.However,this approach carries significant technical challenges,particularly for protein cargos.We have focused on the development of nanoscale cocrystalline protein depots,known as PODS®,that contain protein cargos,including cytokines.Here,we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes,such as highly sustained release of cargo,that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery.Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response.Moreover,the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic cells.The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.
