6533b7d3fe1ef96bd1260caf

RESEARCH PRODUCT

Adult rat myelin enhances axonal outgrowth from neural stem cells.

Michael K. E. SchäferGiovanni CoppolaGrace WoodruffMatt HuntMark H. TuszynskiMark H. TuszynskiRichard LieJacob RobinsonCédric G. GeoffroyLutz MenzelRiki KawaguchiPaul LuPaul LuGunnar PoplawskiPhilip CaneteBinhai ZhengHiromi KumamaruJennifer N. Dulin

subject

0301 basic medicineAgingNeuronalNudeMessengerNeurodegenerativeInbred C57BLRegenerative MedicineMedical and Health SciencesMyelinMiceNeural Stem CellsStem Cell Research - Nonembryonic - HumanCyclic AMPAxonPhosphorylationGray MatterInduced pluripotent stem cellExtracellular Signal-Regulated MAP KinasesSpinal Cord InjuryMyelin SheathInbred F344Neuronal growth regulator 1Stem Cell Research - Induced Pluripotent Stem Cell - HumanChemistryGeneral MedicineBiological SciencesWhite MatterNeural stem cellCell biologymedicine.anatomical_structureSpinal Cord5.1 PharmaceuticalsNeurologicalFemaleStem Cell Research - Nonembryonic - Non-HumanDevelopment of treatments and therapeutic interventionsPhysical Injury - Accidents and Adverse EffectsNeuriteCell Adhesion Molecules NeuronalCentral nervous systemNeuronal OutgrowthArticleWhite matter03 medical and health sciencesRats NudemedicineAnimalsHumansRNA MessengerStem Cell Research - Embryonic - HumanTraumatic Head and Spine InjuryTransplantationStem Cell Research - Induced Pluripotent Stem CellNeurosciencesStem Cell ResearchRats Inbred F344AxonsRatsMice Inbred C57BL030104 developmental biologynervous systemChondroitin Sulfate ProteoglycansRNACell Adhesion Molecules

description

Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell-derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon-myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal-regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI.

yearjournalcountryeditionlanguage
2018-05-23
https://escholarship.org/uc/item/6331661x