Effective therapies for peripheral nerve repair are still lacking despite active research in this field over the past years.The limited knowledge of biomolecules that equally promote axon regeneration and glial cell d...Effective therapies for peripheral nerve repair are still lacking despite active research in this field over the past years.The limited knowledge of biomolecules that equally promote axon regeneration and glial cell dynamics,which are critical for nerve regeneration,poses a major challenge in developing effective therapies.Here,we showed that the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor(MANF)equally promotes axon regeneration and glial cell dynamics favorable for nerve regeneration.Using adult rodent models,we showed that the endogenous expression of MANF is restricted to non-peptidergic sensory neurons.However,supplementation of exogenous MANF promoted the growth of all subtypes of adult sensory neurons.We also demonstrated that exogenous MANF promotes the proliferation and migration of adult primary Schwann Cells(SCs).Furthermore,we showed that local and repeated administration of MANF to injured nerves promotes axon regeneration in mice models.Finally,we devised a therapeutic approach by programming nerve-resident SCs to locally and continuously deliver MANF to injured nerves and showed that this approach improves axon regeneration.Overall,this work developed a therapeutic approach by harnessing the power of SCs as a local delivery system for MANF for nerve repair.展开更多
基金supported by the College of Medicine Research Award from the College of Medicine at the University of Saskatchewan to AK(Krishnan)supported by the Natural Sciences and Engineering Research Council(NSERC)of Canada Discovery Launch Supplement(DGECR-2020-00049)to AKthe CoMGRAD fellowship from the College of Medicine to BS.
文摘Effective therapies for peripheral nerve repair are still lacking despite active research in this field over the past years.The limited knowledge of biomolecules that equally promote axon regeneration and glial cell dynamics,which are critical for nerve regeneration,poses a major challenge in developing effective therapies.Here,we showed that the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor(MANF)equally promotes axon regeneration and glial cell dynamics favorable for nerve regeneration.Using adult rodent models,we showed that the endogenous expression of MANF is restricted to non-peptidergic sensory neurons.However,supplementation of exogenous MANF promoted the growth of all subtypes of adult sensory neurons.We also demonstrated that exogenous MANF promotes the proliferation and migration of adult primary Schwann Cells(SCs).Furthermore,we showed that local and repeated administration of MANF to injured nerves promotes axon regeneration in mice models.Finally,we devised a therapeutic approach by programming nerve-resident SCs to locally and continuously deliver MANF to injured nerves and showed that this approach improves axon regeneration.Overall,this work developed a therapeutic approach by harnessing the power of SCs as a local delivery system for MANF for nerve repair.
