Olfactory Ensheathing Cells: Part I—Current Concepts and Experimental Laboratory Models

Gladwin, Karen; Choi, David

doi:10.1016/j.wneu.2013.03.010

Cited by 12 publications

(15 citation statements)

References 61 publications

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“…The life span of OSNs is relatively short, around 30 days in young mammals (Brann & Firestein, ), and so there is a need for continual neurogenesis in order to maintain a normal sense of smell. Harnessing the unusual neuroregenerative abilities of the olfactory system continues to be promoted as a therapeutic approach to the reversal of spinal cord injury and certain demyelinating conditions (Assinck, Duncan, Hilton, Plemel, & Tetzlaff, ; Ekberg & St John, ; Gladwin & Choi, ; Gomez et al, ; Yao et al, ). The olfactory mucosa (OM) represents a particularly attractive target for sourcing OECs for clinical transplantation, as it permits relatively noninvasive endoscopic harvesting from affected patients, healthy volunteers, or cadaveric specimens (Andrews, Poirrier, Lund, & Choi, ; Choi & Gladwin, ).…”

Section: Introductionmentioning

confidence: 99%

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

Smith

Whitcroft

Law

et al. 2019

J of Neuroscience Research

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Transplantation of olfactory ensheathing cells (OECs) is a potential therapy for the regeneration of damaged neurons. While they maintain tissue homeostasis in the olfactory mucosa (OM) and olfactory bulb (OB), their regenerative properties also support the normal sense of smell by enabling continual turnover and axonal regrowth of olfactory sensory neurons (OSNs). However, the molecular physiology of OECs is not fully understood, especially that of OECs from the mucosa. Here, we carried out whole‐cell patch‐clamp recordings from individual OECs cultured from the OM and OB of the adult rat, and from the human OM. A subset of OECs from the rat OM cultured 1–3 days in vitro had large weakly rectifying K+ currents, which were sensitive to Ba2+ and desipramine, blockers of Kir4‐family channels. Kir4.1 immunofluorescence was detectable in cultured OM cells colabeled for the OEC marker S100, and in S100‐labeled cells found adjacent to OSN axons in mucosal sections. OECs cultured from rat OB had distinct properties though, displaying strongly rectifying inward currents at hyperpolarized membrane potentials and strongly rectifying outward currents at depolarized potentials. Kir4.1 immunofluorescence was not evident in OECs adjacent to axons of OSNs in the OB. A subset of human OECs cultured from the OM of adults had membrane properties comparable to those of the rat OM that is dominated by Ba2+‐sensitive weak inwardly rectifying currents. The membrane properties of peripheral OECs are different to those of central OECs, suggesting they may play distinct roles during olfaction.

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Section: Introductionmentioning

confidence: 99%

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

Smith

Whitcroft

Law

et al. 2019

J of Neuroscience Research

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“…Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function, and connections. Major advances in our understanding of neuroplasticity have, to date, yielded few established interventions [4][5][6]42,[55][56][57][58]77,78,[80][81][82][83][84][85][86], Brunelli decided on a total neurotransmitter switch at the neuromuscular junction from cholinergic to glutamatergic [11,[71][72][73]. In contrast to the GB group, we did not observe any FB+ neurons in the brain, but we did observe them in many laminae of the SC gray matter.…”

Section: Discussionmentioning

confidence: 71%

“…Until now, traumatic paraplegia by severance of the spinal cord (SC) remains an irreversible condition. Basically, current clinical treatment strategies are targeted to promote axon regeneration and outgrowth beyond the scar formation following SC avulsion [1][2][3][4][5][8][9][10][11][12][13][14][15][16][17][18][20][21][24][25][26][27][28][29][30][31][72][73][74][75][76][77][78][79][80][81][82][83][84][85] Previous experimental and clinical studies together with GB have aroused some hope that paraplegic patients might achieve some selective voluntary muscle reinnervation after grafting the first motor neuron to skeletal hip muscles [10,11,25,72,73].…”

Section: Discussionmentioning

confidence: 99%

“…Spinal cord plasticity can evolve regenerative mechanisms that are normally suppressed by multiple extrinsic and intrinsic factors but can be activated by injury to stimulate neural growth and proliferation [20,21]. The additional beneficial effects of olfactory stem cell transplantation in animal experiments and human SCI, although still limited, have been reported [5][6][7][26][27][28][29]78,85].…”

Section: Discussionmentioning

confidence: 99%

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New Aspects of Graft-induced Central Plasticity and Neuroregeneration at T 10 in a Rat Model†

Wild¹,

Cătoi²,

Wild³

et al. 2017

J Neurol Neurophysiol

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Objective: Retest Brunelli's graft induced glutamate neurotransmitter switch at the neuromuscular junction in rat for the translation of new aspects of central plasticity concepts for human reconstructive surgery in spinal cord lesions. Methods:Randomized double blind controlled study in rat, which was limited to 30 animals (Charles River, 220 to 280 g). Ethical research approval was obtained from the Animal Research Committee of the University Hospital Schleswig Holstein, UK-SH, Lübeck, D, and legitimated by the Governmental Department of Agriculture, Natural Environments and Agriculture Kiel, D, in compliance with the European Commission Recommendation to retest and review of graft-induced glutamatergic regeneration and /or cholinergic co-transmission at the neuromuscular junction for reinnervation of the skeletal internal obliquus abdominal muscle fibres. Assessments were performed to demonstrate pharmacological neuromodulation after attaching the lateral corticospinal tract at T10 to the bisected skeletal motor nerve. Medication was administered for 14 days postoperatively-a) verum Cerebrolysin ® IP=12-b) shams NaCl 0.9% IP=11, and c) 7 controls (nil). 2nd Op at day 90 (16 surviving rats) for open proof of reinnervation and its type by a) CMAP, b)Vecuronium ® application. Fast Blue ® labeling were performed. 10 days later, on the 3rd Op N=15, euthanasia and organ fixation were performed. Extensive histology-morphology examinations were performed in Cluj.Results: Eight rats showed positive CMAPs. Reinnervation and neuromodulation were demonstrated by counting and comparison of the grafted muscle fibers diameter. Four CAMP-positive-rats received Vecuronium ® : 1 CERE and 1 NaCl each demonstrated a loss of amplitude respectively two an incomplete muscle blockage due to the coexistence of glutamatergic and cholinergic neurotransmission. Confirmation of the VGluT2 in axons was observed by immunofluorescence. FB+ neurons were observed in many Rexed laminae in grafted spinal cord, but not in the brain. Conclusion:The coexistence of graft-induced cholinergic and glutamatergic neurotransmission and a great capacity of lower motor neurons and other types of spinal neurons to regenerate were observed. Because of limited animals, pharmacological neuromodulation requires further investigation.

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“…For over two decades researchers have been studying the therapeutic potential of olfactory ensheathing cells (OECs) to treat traumatic injuries to the central nervous system (Barnett and Riddell 2007; Mackay-Sim and St John 2011; Raisman et al 2012; Gladwin and Choi 2015). OECs are unique glial cells that exist exclusively within the olfactory system and perform a vital role in supporting the continual turnover of short-lived olfactory receptor neurons (ORNs) throughout adult life (Doucette 1993).…”

Section: Introductionmentioning

confidence: 99%

Common olfactory ensheathing glial markers in the developing human olfactory system

2016

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The in situ immunocytochemical properties of olfactory ensheathing cells (OECs) have been well studied in several small to medium sized animal models including rats, mice, guinea pigs, cats and canines. However, we know very little about the antigenic characteristics of OECs in situ within the adult and developing human olfactory bulb and nerve roots. To address this gap in knowledge we undertook an immunocytochemical analysis of the 11–19 pcw human foetal olfactory system. Human foetal OECs in situ possessed important differences compared to rodents in the expression of key surface markers. P75NTR was not observed in OECs but was strongly expressed by human foetal Schwann cells and perineurial olfactory nerve fibroblasts surrounding OECs. We define OECs throughout the 11–19 pcw human olfactory system as S100/vimentin/SOX10+ with low expression of GFAP. Our results suggest that P75NTR is a robust marker that could be utilised with cell sorting techniques to generate enriched OEC cultures by first removing P75NTR expressing Schwann cells and fibroblasts, and subsequently to isolate OECs after P75NTR upregulation in vitro. O4 and PSA-NCAM were not found to be suitable surface antigens for OEC purification owing to their ambiguous and heterogeneous expression. Our results highlight the importance of corroborating cell markers when translating cell therapies from animal models to the clinic.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-016-1313-y) contains supplementary material, which is available to authorized users.

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Olfactory Ensheathing Cells: Part I—Current Concepts and Experimental Laboratory Models

Cited by 12 publications

References 61 publications

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

New Aspects of Graft-induced Central Plasticity and Neuroregeneration at T 10 in a Rat Model†

Common olfactory ensheathing glial markers in the developing human olfactory system

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