As ingenious as nature's invention of myelin sheaths within the mammalian nervous system is, as fatal can be damage to this specialized lipid structure. Long-term loss of electrical insulation and of further supporti...As ingenious as nature's invention of myelin sheaths within the mammalian nervous system is, as fatal can be damage to this specialized lipid structure. Long-term loss of electrical insulation and of further supportive functions myelin provides to axons, as seen in demyelinating diseases such as multiple sclerosis (MS), leads to neurodegeneration and results in progressive disabilities. Multiple lines of evidence have demon-strated the increasing inability of oligodendrocyte precursor cells (OPCs) to replace lost oligodendrocytes (OLs) in order to restore lost myelin. Much research has been dedicated to reveal potential reasons for this regeneration deficit but despite promising approaches no remyelination-promoting drugs have successfully been developed yet. In addition to OPCs neural stem cells of the adult central nervous system also hold a high potential to generate myelinating OLs. There are at least two neural stem cell niches in the brain, the subventricular zone lining the lateral ventricles and the subgranular zone of the dentate gyrus, and an additional source of neural stem cells has been located in the central canal of the spinal cord. While a substantial body of literature has described their neurogenic capacity, still little is known about the oligodendrogenic potential of these cells, even if some animal studies have provided proof of their contribution to remyelination. In this review, we summarize and discuss these studies, taking into account the different niches, the heterogeneity within and between stem cell niches and present current strategies of how to promote stem cell-mediated myelin repair.展开更多
Schwann cells are the myelinating glial cells of the peripheral nervous system(PNS).By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated...Schwann cells are the myelinating glial cells of the peripheral nervous system(PNS).By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated-a process referred to as saltatory signal propagation.Apart from this prominent physiological function,these cells also exert important pathophysiological roles in PNS injuries or dis- eases. In contrast to the central nervous system (CNS), the adult PNS retains a remarkably high degree of intrinsic re- generation. As a consequence, transected axons and dam- aged myelin sheaths can be repaired and nerve functional- ity can be restored. This spontaneous regenerative capacity depends on (inter) actions of macrophages, neurons, and Schwann cells.展开更多
基金The German Academic Exchange Service (DAAD) supported RAsupported by grants to PK by the German Research Council (DFG+3 种基金 SPP1757/KU1934/2_1, KU1934/5-1)the Christiane and Claudia Hempel Foundation for clinical stem cell research and Young Gliasupported in part by the Walter and Ilse Rose Foundationthe James and Elisabeth Cloppenburg, Peek & Cloppenburg Düsseldorf Foundation
文摘As ingenious as nature's invention of myelin sheaths within the mammalian nervous system is, as fatal can be damage to this specialized lipid structure. Long-term loss of electrical insulation and of further supportive functions myelin provides to axons, as seen in demyelinating diseases such as multiple sclerosis (MS), leads to neurodegeneration and results in progressive disabilities. Multiple lines of evidence have demon-strated the increasing inability of oligodendrocyte precursor cells (OPCs) to replace lost oligodendrocytes (OLs) in order to restore lost myelin. Much research has been dedicated to reveal potential reasons for this regeneration deficit but despite promising approaches no remyelination-promoting drugs have successfully been developed yet. In addition to OPCs neural stem cells of the adult central nervous system also hold a high potential to generate myelinating OLs. There are at least two neural stem cell niches in the brain, the subventricular zone lining the lateral ventricles and the subgranular zone of the dentate gyrus, and an additional source of neural stem cells has been located in the central canal of the spinal cord. While a substantial body of literature has described their neurogenic capacity, still little is known about the oligodendrogenic potential of these cells, even if some animal studies have provided proof of their contribution to remyelination. In this review, we summarize and discuss these studies, taking into account the different niches, the heterogeneity within and between stem cell niches and present current strategies of how to promote stem cell-mediated myelin repair.
基金supported by grants from the DFG(German Research Council)Novartis Pharma Gmb H(Nürnberg+2 种基金Germany)Baxter Innovations Gmb H(ViennaGermany)
文摘Schwann cells are the myelinating glial cells of the peripheral nervous system(PNS).By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated-a process referred to as saltatory signal propagation.Apart from this prominent physiological function,these cells also exert important pathophysiological roles in PNS injuries or dis- eases. In contrast to the central nervous system (CNS), the adult PNS retains a remarkably high degree of intrinsic re- generation. As a consequence, transected axons and dam- aged myelin sheaths can be repaired and nerve functional- ity can be restored. This spontaneous regenerative capacity depends on (inter) actions of macrophages, neurons, and Schwann cells.