Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration.

Abstract:

:Based on their differentiation ability, bone marrow stromal cells (MSCs) are a good source for cell therapy. Using a cynomolgus monkey peripheral nervous system injury model, we examined the safety and efficacy of Schwann cells induced from MSCs as a source for auto-cell transplantation therapy in nerve injury. Serial treatment of monkey MSCs with reducing agents and cytokines induced their differentiation into cells with Schwann cell properties at a very high ratio. Expression of Schwann cell markers was confirmed by both immunocytochemistry and reverse transcription-polymerase chain reaction. Induced Schwann cells were used for auto-cell transplantation into the median nerve and followed-up for 1year. No abnormalities were observed in general conditions. Ki67-immunostaining revealed no sign of massive proliferation inside the grafted tube. Furthermore, (18)F-fluorodeoxygluocose-positron emission tomography scanning demonstrated no abnormal accumulation of radioactivity except in regions with expected physiologic accumulation. Restoration of the transplanted nerve was corroborated by behavior analysis, electrophysiology and histological evaluation. Our results suggest that auto-cell transplantation therapy using MSC-derived Schwann cells is safe and effective for accelerating the regeneration of transected axons and for functional recovery of injured nerves. The practical advantages of MSCs are expected to make this system applicable for spinal cord injury and other neurotrauma or myelin disorders where the acceleration of regeneration is expected to enhance functional recovery.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Wakao S,Hayashi T,Kitada M,Kohama M,Matsue D,Teramoto N,Ose T,Itokazu Y,Koshino K,Watabe H,Iida H,Takamoto T,Tabata Y,Dezawa M

doi

10.1016/j.expneurol.2010.01.022

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

537-47

issue

2

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(10)00042-7

journal_volume

223

pub_type

杂志文章
  • Corticosteroid therapy in avian muscular dystrophy: evaluation by magnetic resonance relaxation times.

    abstract::Genetically dystrophic chicks (line 413) were administered 0.3 mg/kg dexamethasone (DEX), a corticosteroid, from 2 to 28 days ex ovo. Diluent-injected dystrophic and normal (line 412) chicks served as controls. The effects of DEX on muscle function were evaluated weekly by the exhaustion score (ES) method. Proton magn...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(88)90096-9

    authors: Misra LK,Entrikin RK

    更新日期:1988-11-01 00:00:00

  • Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

    abstract::Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disea...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审

    doi:10.1016/j.expneurol.2015.06.015

    authors: Washington PM,Villapol S,Burns MP

    更新日期:2016-01-01 00:00:00

  • Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein.

    abstract::Intranuclear inclusion bodies are a shared pathological feature of Huntington's disease (HD) and its transgenic mouse model. Using a panel of antibodies spanning the entire huntingtin molecule, we have investigated the pattern of immunoreactivity within the intranuclear inclusions in the frontal cortex and striatum of...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.1998.7005

    authors: Sieradzan KA,Mechan AO,Jones L,Wanker EE,Nukina N,Mann DM

    更新日期:1999-03-01 00:00:00

  • Spatial distribution of modalities and receptive fields in sensorimotor cortex of awake cats.

    abstract::A sample of 504 single neurons isolated in three curvilinear arrays of 10 closely spaced tracks in primary somatosensory and in pericruciate sensorimotor cortex was studied in two awake, restrained domestic cats. Modality sensitivity and receptive field size and location were assessed for each neuron, along with respo...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(90)90065-z

    authors: Slimp JC,Towe AL

    更新日期:1990-01-01 00:00:00

  • The role of growth factors as a therapeutic approach to demyelinating disease.

    abstract::A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions such as are evident in Multiple Sclerosis (MS). This review focuses on five such proteins that are present in the lesion site and impact oligodendroc...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审

    doi:10.1016/j.expneurol.2016.02.023

    authors: Huang Y,Dreyfus CF

    更新日期:2016-09-01 00:00:00

  • Effect of 192 IgG-saporin on circadian activity rhythms, expression of P75 neurotrophin receptors, calbindin-D28K, and light-induced Fos in the suprachiasmatic nucleus in rats.

    abstract::Photic entrainment of circadian rhythms in mammals is mediated through a direct retinal projection to the core region of the suprachiasmatic nucleus (SCN), the circadian clock. A proportion of this projection contains the low-affinity p75 neurotrophic receptor (p75NTR). Neonatal monosodium glutamate (MSG) treatment, w...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.2002.7969

    authors: Beaulé C,Amir S

    更新日期:2002-08-01 00:00:00

  • The effect of hemorrhage on the development of the postnatal mouse cerebellum.

    abstract::Recent studies have shown that hemorrhagic injury in the preterm cerebellum leads to long-term neurological sequelae, such as motor, affective, and cognitive dysfunction. How cerebellar hemorrhage (CBH) affects the development and function of the cerebellum is largely unknown. Our study focuses on developing a mouse m...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2013.11.010

    authors: Yoo JY,Mak GK,Goldowitz D

    更新日期:2014-02-01 00:00:00

  • Extent of pre-operative L-DOPA-induced dyskinesia predicts the severity of graft-induced dyskinesia after fetal dopamine cell transplantation.

    abstract::Graft-induced dyskinesia has emerged as a problematic side effect after transplantation of fetal dopamine cells into the striatum of patients with Parkinson's disease. These adverse effects of dystonic and choreatiform hyperkinesias that persisted even after withdrawal of L-DOPA medication are not yet fully understood...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2011.09.017

    authors: García J,Carlsson T,Döbrössy M,Nikkhah G,Winkler C

    更新日期:2011-12-01 00:00:00

  • Neurotrophin ligand-receptor systems in somatosensory cortex of adult rat are affected by repeated episodes of ethanol.

    abstract::Ethanol exposure profoundly affects learning and memory and neural plasticity. Key players underlying these functions are neurotrophins. The present study explored the effects of ethanol on the distribution of neurotrophins in the cerebral cortex of the adult rat. Age- and weight-matched pairs of adult male, Long-Evan...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2006.12.022

    authors: Bruns MB,Miller MW

    更新日期:2007-04-01 00:00:00

  • Low-doses of cisplatin injure hippocampal synapses: a mechanism for 'chemo' brain?

    abstract::Chemotherapy-related cognitive deficits are a major neurological problem, but the underlying mechanisms are unclear. The death of neural stem/precursor cell (NSC) by cisplatin has been reported as a potential cause, but this requires high doses of chemotherapeutic agents. Cisplatin is frequently used in modern oncolog...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2014.02.020

    authors: Andres AL,Gong X,Di K,Bota DA

    更新日期:2014-05-01 00:00:00

  • Quantitative biochemical and ultrastructural comparison of mitochondrial permeability transition in isolated brain and liver mitochondria: evidence for reduced sensitivity of brain mitochondria.

    abstract::Opening of the mitochondrial permeability transition pore has increasingly been implicated in excitotoxic, ischemic, and apoptotic cell death, as well as in several neurodegenerative disease processes. However, much of the work directly characterizing properties of the transition pore has been performed in isolated li...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.2000.7438

    authors: Berman SB,Watkins SC,Hastings TG

    更新日期:2000-08-01 00:00:00

  • Tooth pulp-evoked jaw-opening reflex in the cat: evidence for central facilitation induced by noxious discharge in the intradental nerve fibers.

    abstract::The tooth pulp-evoked jaw-opening reflex was studied in the barbiturate-anesthetized cat. At liminal intensity of the stimulus, a stable short-latency response was obtained in the digastricus and in the tongue. At a higher stimulus intensity, there occasionally appeared to be a prolonged discharge of variable duration...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(86)90135-4

    authors: Pertovaara A,Huopaniemi T,Aukee K

    更新日期:1986-04-01 00:00:00

  • Adenosine and propentofylline inhibit the proliferation of cultured microglial cells.

    abstract::Propentofylline is a xanthine derivative that has been known to protec t neurons against ischemia-induced damage. To assess its neuroprotective mechanisms, we examined the effect of propentofylline on microglial proliferation that is thought to play an important role in neuronal damage. We determined the proliferation...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.1996.0035

    authors: Si QS,Nakamura Y,Schubert P,Rudolphi K,Kataoka K

    更新日期:1996-02-01 00:00:00

  • Desmoplakin is involved in organization of an adhesion complex in peripheral nerve regeneration after injury.

    abstract::Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. In this study, we analyzed the expression and function of desmoplakin in peripheral nerve regeneration. Desmo...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2014.12.005

    authors: Gess B,Röhr D,Lange E,Halfter H,Young P

    更新日期:2015-02-01 00:00:00

  • Functional MRI at 4.7 tesla of the rat brain during electric stimulation of forepaw, hindpaw, or tail in single- and multislice experiments.

    abstract::Stimulation of peripheral nerves activates corresponding regions in sensorimotor cortex. We have applied functional magnetic resonance imaging (fMRI) techniques to monitor activated brain regions by means of measuring changes of blood oxygenation level-dependent contrast during electric stimulation of the forepaw, hin...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.2000.7524

    authors: Spenger C,Josephson A,Klason T,Hoehn M,Schwindt W,Ingvar M,Olson L

    更新日期:2000-12-01 00:00:00

  • Effects of accumulation of phosphocreatine on utilization and restoration of high-energy phosphates during anoxia and recovery in thin hippocampal slices from the guinea pig.

    abstract::Effects of accumulation of phosphocreatine (P-creatine) on utilization and restoration of high-energy phosphates during anoxia and recovery were studied using thin hippocampal slices from the guinea pig. Incubation of slices with creatine (5 to 30 mM) increased the content of tissue P-creatine, in a linear fashion, an...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(83)90256-x

    authors: Yoneda K,Arakawa T,Asaoka Y,Fukuoka Y,Kinugasa K,Takimoto K,Okada Y

    更新日期:1983-10-01 00:00:00

  • Tyrosine hydroxylase is expressed in a subpopulation of small dorsal root ganglion neurons in the adult mouse.

    abstract::The expression of tyrosine hydroxylase (TH) was studied in adult mouse dorsal root ganglia (DRGs) and spinal cord by means of immunohistochemistry and in situ hybridization. TH immunoreactivity and TH mRNA were present in 10-15% of lumbar DRG neurons, in most cases being small/medium-sized. Only very few of these neur...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2006.01.023

    authors: Brumovsky P,Villar MJ,Hökfelt T

    更新日期:2006-07-01 00:00:00

  • Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset.

    abstract::Sleep and behavioral monitoring of young mice is necessary for understating the progress of symptoms in congenital and acquired diseases associated with sleep and movement disorders. In the current study, we have developed a non-invasive sleep monitoring system that identifies wake and sleep patterns of newborn mice u...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2014.08.004

    authors: Sato M,Sagawa Y,Hirai N,Sato S,Okuro M,Kumar S,Kanbayashi T,Shimizu T,Sakai N,Nishino S

    更新日期:2014-11-01 00:00:00

  • Restitution of functional neural connections in chick embryos assessed in vitro after spinal cord transection in Ovo.

    abstract::Functional neural reconnection is not common after spinal cord transection in the CNS of adult higher vertebrates but has been demonstrated in embryonic avian and neonatal mammalian CNS. Chick brainstem spinal cord preparations from nontransected controls and embryos transected at the cervical level on embryonic days ...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.1998.6944

    authors: Sholomenko GN,Delaney KR

    更新日期:1998-12-01 00:00:00

  • Impact of inhibition of erythropoietin treatment-mediated neurogenesis in the dentate gyrus of the hippocampus on restoration of spatial learning after traumatic brain injury.

    abstract::Our previous study demonstrates that delayed (initiated 24h post injury) erythropoietin (EPO) therapy for traumatic brain injury (TBI) significantly improves spatial learning. In this study, we investigated the impact of inhibition of EPO treatment-mediated neurogenesis on spatial learning after experimental TBI. Youn...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2012.02.015

    authors: Zhang Y,Chopp M,Mahmood A,Meng Y,Qu C,Xiong Y

    更新日期:2012-05-01 00:00:00

  • Alterations in voluntary movement execution in Huntington's disease are related to the dominant motor system: evidence from event-related potentials.

    abstract::Huntington's disease is an autosomal dominant neurogenetic disorder leading to striatal atrophy, characterized by involuntary movements. Voluntary movements also deteriorate, but the neurophysiological mechanisms are less understood. We investigated voluntary movement execution and its neural correlates by means of mo...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2008.11.018

    authors: Beste C,Konrad C,Saft C,Ukas T,Andrich J,Pfleiderer B,Hausmann M,Falkenstein M

    更新日期:2009-03-01 00:00:00

  • Neurite outgrowth is enhanced by anti-idiotypic monoclonal antibodies to the ganglioside GM1.

    abstract::Exogenously added gangliosides enhance sprouting, neurite outgrowth, and other neuronal activities; this effect may be initiated when a ganglioside binds to a membrane protein or when a ganglioside intercalates into the plasma membrane. To test whether binding to membrane proteins is sufficient for ganglioside-mediate...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.1997.6459

    authors: Riggott MJ,Matthew WD

    更新日期:1997-05-01 00:00:00

  • Cordotomy-denervation interactions on contractile and myofibrillar properties of fast and slow muscles in the rat.

    abstract::Cordotomy-denervation interactions were studied on contractile and myofibrillar properties of slow (soleus) and fast (extensor digitorum longus) muscles of the rat. The spinal cord was transected midthoracically in neonatal (2-day-old) animals. Two months after birth, a unilateral transection of the sciatic nerve was ...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(88)90214-2

    authors: Midrio M,Danieli Betto D,Betto R,Noventa D,Antico F

    更新日期:1988-04-01 00:00:00

  • Unilateral interruption of geniculate and callosal inputs to the visual cortex of cats: ocular dominance and responsiveness of cells in the deafferented and in the intact hemispheres.

    abstract::In order to study the ocular dominance and responsiveness of cells in the deafferented visual cortex, the geniculate and the callosal inputs were interrupted in adult cats by either simultaneous (OTCCX) or separate surgical transection of the optic tract (OTX) and the posterior corpus callosum (CCX). Unit recording wa...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(88)90174-4

    authors: Yinon U,Achiron A

    更新日期:1988-03-01 00:00:00

  • Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells.

    abstract::Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothromb...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2017.10.013

    authors: Yang L,Tucker D,Dong Y,Wu C,Lu Y,Li Y,Zhang J,Liu TC,Zhang Q

    更新日期:2018-01-01 00:00:00

  • Electrophysiology and morphometry of the Aalpha- and Abeta-fiber populations in the normal and regenerating rat sciatic nerve.

    abstract::We studied electrophysiological and morphological properties of the Aalpha- and Abeta-fibers in the regenerating sciatic nerve to establish whether these fiber types regenerate in numerical proportion and whether and how the electrophysiological properties of these fiber types are adjusted during regeneration. Compoun...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2004.01.019

    authors: Vleggeert-Lankamp CL,van den Berg RJ,Feirabend HK,Lakke EA,Malessy MJ,Thomeer RT

    更新日期:2004-06-01 00:00:00

  • Progesterone and allopregnanolone exacerbate hypoxic-ischemic brain injury in immature rats.

    abstract::Progesterone and its metabolite, allopregnanolone, are neurosteroids that are present at high concentrations in fetal brains that decrease right after birth. Allopregnanolone is a potent positive modulator of γ-aminobutyric acid A (GABA(A)) receptor function. We examined the effect of exogenous administration of these...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2011.10.004

    authors: Tsuji M,Taguchi A,Ohshima M,Kasahara Y,Ikeda T

    更新日期:2012-01-01 00:00:00

  • Unilateral ibotenic acid lesion of the caudate putamen results in D2 receptor alterations on the contralateral side.

    abstract::Dopaminergic projections to the caudate putamen (CPu) involve fibers in the nigrostriatal pathway from the ipsilateral substantia nigra-pars compacta. Post-synaptic receptor populations on cells receiving this information are composed of both D1 and D2 dopamine receptor subtypes. In the present study, unilateral lesio...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1006/exnr.1993.1069

    authors: Narang N,Hunt ME,Pundt LL,Alburges ME,Wamsley JK

    更新日期:1993-05-01 00:00:00

  • Heparin stabilizes FGF-2 and modulates striatal precursor cell behavior in response to EGF.

    abstract::Fibroblast and epidermal growth factors (FGF-2 and EGF) are powerful mitogens for neural precursor cells isolated from the developing striatum and grown as neurospheres. However, questions remain as to the exact role of each of these molecules, and how the proteoglycan heparin may modify their behavior. Here, we show ...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/j.expneurol.2004.05.007

    authors: Caldwell MA,Garcion E,terBorg MG,He X,Svendsen CN

    更新日期:2004-08-01 00:00:00

  • Long-term cross-species brain transplantation of a polymer-encapsulated dopamine-secreting cell line.

    abstract::Cross-species transplantation of dopamine-releasing cell lines protected against immune rejection by a semi-permeable synthetic membrane may provide a source of neurotransmitters for the treatment of Parkinson's disease. Experiments were carried out to assess whether polymer-encapsulated PC12 cells, a catecholaminergi...

    journal_title:Experimental neurology

    pub_type: 杂志文章

    doi:10.1016/0014-4886(91)90093-r

    authors: Aebischer P,Tresco PA,Winn SR,Greene LA,Jaeger CB

    更新日期:1991-03-01 00:00:00