Olfactory ensheathing cell

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Neuroglia of the brain shown by Golgi's method Neuroglia.png
Neuroglia of the brain shown by Golgi's method

Olfactory ensheathing cells (OECs), also known as olfactory ensheathing glia or olfactory ensheathing glial cells, are a type of macroglia (radial glia) found in the nervous system. They are also known as olfactory Schwann cells, because they ensheath the non-myelinated axons of olfactory neurons in a similar way to which Schwann cells ensheath non-myelinated peripheral neurons. They also share the property of assisting axonal regeneration.

Contents

OECs are capable of phagocytosing axonal debris in vivo, and in vitro they phagocytose bacteria. Olfactory glia that express the antimicrobial enzyme lysozyme (LYZ) are thought to play an important role in immunoprotection in the mucosa, where neurons are directly exposed to the external environment.

OECs have been tested successfully in experimental axonal regeneration in adult rats with traumatic spinal cord damage, and clinical trials are currently being conducted to obtain more information on spinal cord injuries and other neurodegenerative diseases.

Origin

Embryonic development in the central nervous system Embryonic Development CNS.png
Embryonic development in the central nervous system

In the peripheral nervous system OECs are dispersed within the olfactory epithelium and the olfactory nerve. In the central nervous system, OECs are found within the outer two layers of the olfactory bulb. During development, primitive olfactory neurons extend their axons from the olfactory placode, through the mesenchyme, towards the telencephalic vesicle. [1] After reaching the telencephalic vesicle, a small layer of cells and axons cover the vesicle. Olfactory axons invade the basal lamina of the glia limitans and the olfactory bulb to create the olfactory nerve and glomerular layers. A fraction of the epithelial migrating precursors give rise to olfactory ensheathing glia that inhabit the olfactory nerve and glomerular layers. [1] OECs and astrocytes interact with each other to form a new glia limitans. [1] OECs are distinct from other glia in their developmental origin for they are present in the peripheral nervous system as well as the central nervous system. They also form on bundles of olfactory sensory neuron axons in a manner distinct from myelination.

Functions

OECs are radial glia that perform a variety of functions. Within the olfactory system they phagocytose axonal debris and dead cells. When cultured in a petri dish (in vitro), they phagocytose bacteria. Multiple studies have shown that OECs may assist in treating spinal cord injury (SCI) due to their regenerate properties in the peripheral nervous system and their presence in the central nervous system. [2] OECs are also known to support and guide olfactory axons, grow through glial scars, and secrete many neurotrophic factors. [3]

OECs express glial markers such as glial fibrillary acidic protein, s100, and p75, and radial glial markers such as nestin and vimentin, which may further assist researchers with understanding the labeling characteristics of these specialized glia.

Olfactory system regeneration

Plan of olfactory neurons Gray772.png
Plan of olfactory neurons

The mammalian olfactory system is unusual in that it has the ability to continuously regenerate its neurons during adulthood. [4] This ability is associated with olfactory ensheathing glia. New olfactory receptor neurons must project their axons through the central nervous system to an olfactory bulb in order to be functional. The growth and regeneration of olfactory axons can be attributable to OECs, as they form the fascicles through which axons grow from the peripheral nervous system into the central nervous system. [5] Olfactory receptor neurons have an average lifespan of 6–8 weeks and therefore must be replaced by cells differentiated from the stem cells that are within a layer at the nearby epithelium's base. Axonal growth is guided by the glial composition and cytoarchitecture of the olfactory bulb in addition to the presence of OECs. [4]

OECs are thought to be in part responsible for the neurogenesis of primary olfactory neurons through the processes of fasciculation, cell sorting, and axonal targeting. [6]

Role in spinal cord injuries

Traumatic spinal cord damage causes a permanent loss of motor and sensory functions in the central nervous system, termed paraplegia or tetraplegia based on the site of the injury. Other detrimental effects may take place in the respiratory system and renal system as a result of the injury. Unlike the peripheral nervous system, the central nervous system is unable to regenerate damaged axons, so its synaptic connections are lost forever. Current treatment is limited and the primary potential methods are either controversial or noneffective. Studies dating back to the 1990s have begun researching the olfactory system of mammals, rats in particular, to gain a greater understanding of axonal regeneration and neurogenesis, and the possible implementation of these cells at the site of the spinal cord injury.

Transplantation of OECs into the spinal cord has become a possible therapy for spinal cord damage and other neural diseases in animal models. Several recent studies have reported that preventing OEC inhibition will present a uniform population of cells in the spinal cord, creating an environment in which damaged axons can be repaired. In October 2014, the Polish firefighter Darek Fidyka became the first paraplegic patient to regain mobility after OEC transplantation. [7] [8]

OECs are similar to Schwann cells in that they provide an upregulation of low-affinity NGF receptor p75 following injury; however, unlike Schwann cells they produce lower levels of neurotrophins. Several studies have shown evidence of OECs being able to support regeneration of lesioned axons, but these results are often unable to be reproduced. [4] Regardless, OECs have been investigated thoroughly in relation to spinal cord injuries, amyotrophic lateral sclerosis, and other neurodegenerative diseases. Researchers suggest that these cells possess a unique ability to remyelinate injured neurons. [9]

Peptide-modified gellan gum and OECs

Stem cell transplantation has been identified as another possible therapy for axonal regeneration in the central nervous system by delivering these cells directly to the site of the spinal cord injury. Both OECs and neural stem/progenitor cells (NSPCs) have been successfully transplanted in the central nervous system of adult rats and have had either positive or neutral results as a method of neurogenesis and axonal regeneration; however, neither method has been shown to have long term beneficial effects, as cell survival is usually less than 1% after transplantation. [3] The inability of these cells to sustain after transplantation is a result of inflammation, the inability of a sufficient matrix to thrive and create a uniform population of cells, or the migratory response of the cells needed to fully repair the site of the injury. Another current issue with the survival of the cells is utilizing the proper biomaterials to deliver them to the site of the injury.

One study has investigated the use of peptide modified gellan gum as the biomaterial with OECs and neural stem/progenitor cells to provide an environment that will allow these cells to survive after transplantation. [3] Gellan gum hydrogel can be injected in a minimally invasive manner and is approved by the FDA as a food additive because of its chemical structure. The gellan gum was modified with several fibronectin-derived peptide sequences so the transplantation cells have closely related properties to that of native tissue in the extracellular matrix. [3] By mimicking native tissue, the delivery cells are less likely to be rejected by the body and biological functions such as cell adhesion and growth will be enhanced through cell-cell and cell-matrix interactions. In order to determine the possibility of OECs and NPSCs improving cell viability, both cells were co-cultured in direct contact with each other, along with the peptide-modified gellan gum. [3]

The experiment demonstrated that NSPC adhesion, proliferation, and viability are greatly increased when the peptide-modified gellan gum is used as the transplantation device when compared to a gellan gum control. [3] Additionally, the co-culture of OECs and NSPCs shows greater cell survival compared to the cell survival of NSPCs cultured alone. The results provide evidence that this method of cell transplantation is a potential strategy for repairing spinal cord damage in the future.

Side effects of cell transplantation

A study has shown that cell transplantation may cause an increase in body temperature of a subject with an older injury to the spinal cord. In this experiment, the patients' body temperatures were elevated to those of a moderate fever after transplantation, and lasted approximately 3–4 days. However, the study provides evidence that even past spinal cord injuries can benefit from the neurological functional recovery that stem cell transplantation may provide in the future. [10]

Transplantation of stem cells is also known to cause toxicity and graft-versus-host disease (GVHD). Apoptotic cells have been administered simultaneously with hematopoietic stem cells in experimental transplantation models, in anticipation of an improved outcome. [11] As a result, the combination prevents alloimmunization, up-regulates Regulatory T cells (suppressor T cells) and reduces the severity of GVHD. [11]

Infection susceptibility

OECs have properties similar to those of astrocytes, [12] both of which have been identified as being susceptible to viral infection. [9] [12]

Labeling OECs

Iron oxide particles for MRI

As stem cell transplantation is becoming a more prevalent means of treating traumatic spinal cord damage, many processes between the start and end result need to be addressed and made more efficient. By labeling OECs, these cells can be tracked by a magnetic resonance imaging (MRI) device when being dispersed in the central nervous system [13] A recent study made use of a novel type of micron-sized particles of iron oxide (MPIO) to label and track these transport-mediated cells via MRI. [13] The experiment resulted in an OEC labeling efficiency of more than 90% with an MPIO incubation time as short as 6 hours, without affecting cell proliferation, migration and viability. [13] MPIOs have also been successfully transplanted into the vitreous body of adult rat eyes, providing the first detailed protocol for efficient and safe MPIO labeling of OECs for their non-invasive MRI tracking in real time for use in studies of central nervous system repair and axonal regeneration. [13]

Subpopulations

Two distinct subpopulations of OECs have been identified [14] with high or low cell surface expression of low-affinity nerve growth factor receptor (p75).

See also

Related Research Articles

Axon Long projection on a neuron that conducts signals to other neurons

An axon, or nerve fiber, is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction has caused many inherited and acquired neurological disorders which can affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

Central nervous system Brain and spinal cord

The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric animals—i.e., all multicellular animals except sponges and jellyfish. It consists of a large nerve running from the anterior to the posterior, with the anterior end is enlarged into the brain. Not all animals with a central nervous system have a brain, although the large majority do.

Myelin Fatty substance that surrounds nerve cell axons to insulate them and increase transmission speed

Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons to insulate them and increase the rate at which electrical impulses are passed along the axon. The myelinated axon can be likened to an electrical wire with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, each myelin sheath insulates the axon over a single long section and, in general, each axon comprises multiple long myelinated sections separated from each other by short myelin sheath-gaps called nodes of Ranvier.

Neuron Electrically excitable cell that communicates via synapses

A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all animals except sponges and placozoa. Plants and fungi do not have nerve cells.

Schwann cell

Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle. The two types of Schwann cells are myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue-specific manner.

Nervous tissue Main component of the nervous system

Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls bodily functions and activity and consists of two parts: the central nervous system (CNS) comprising the brain and spinal cord, and the peripheral nervous system (PNS) comprising the branching peripheral nerves. It is composed of neurons, also known as nerve cells, which receive and transmit impulses, and neuroglia, also known as glial cells or glia, which assist the propagation of the nerve impulse as well as provide nutrients to the neurons.

Motor nerve

A motor nerve is a nerve located in the central nervous system (CNS), usually the spinal cord, that sends motor signals from the CNS to the muscles of the body. This is different from the motor neuron, which includes a cell body and branching of dendrites, while the nerve is made up of a bundle of axons. Motor nerves act as efferent nerves which carry information out from the CNS to muscles, as opposed to afferent nerves, which send signals from sensory receptors in the periphery to the CNS. Efferent nerves can also connect to glands or other organs/issues instead of muscles. In addition, there are nerves that serve as both sensory and motor nerves called mixed nerves.

Glia Support cells in the nervous system

Glia, also called glial cells or neuroglia, are non-neuronal cells in the central nervous system and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons. In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells, and microglia, and in the peripheral nervous system glial cells include Schwann cells and satellite cells. They have four main functions: (1) to surround neurons and hold them in place; (2) to supply nutrients and oxygen to neurons; (3) to insulate one neuron from another; (4) to destroy pathogens and remove dead neurons. They also play a role in neurotransmission and synaptic connections, and in physiological processes like breathing. While glia were thought to outnumber neurons by a ratio of 10:1, recent studies using newer methods and reappraisal of historical quantitative evidence suggests an overall ratio of less than 1:1, with substantial variation between different brain tissues.

Node of Ranvier aspect of anatomy

Nodes of Ranvier, also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, allowing them to participate in the exchange of ions required to regenerate the action potential. Nerve conduction in myelinated axons is referred to as saltatory conduction due to the manner in which the action potential seems to "jump" from one node to the next along the axon. This results in faster conduction of the action potential.

Astrocyte

Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.

Astrogliosis Increase in number of astrocytes due to central nervous system injury

Astrogliosis is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling. Astrogliosis changes the molecular expression and morphology of astrocytes, in response to infection for example, in severe cases causing glial scar formation that may inhibit axon regeneration.

Oligodendrocyte progenitor cell

Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia or polydendrocytes, are a subtype of glial cells in the central nervous system. They are process-bearing glial cells (neuroglia) in the mammalian central nervous system (CNS) that are identified by the expression of the NG2 chondroitin sulfate proteoglycan (CSPG4) and the alpha receptor for platelet-derived growth factor (PDGFRA). They are precursors to oligodendrocytes and may also be able to differentiate into neurons and astrocytes.

Floor plate Embryonic structure

The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions. It has been shown that the floor plate is conserved among vertebrates, such as zebrafish and mice, with homologous structures in invertebrates such as the fruit fly Drosophila and the nematode C. elegans. Functionally, the structure serves as an organizer to ventralize tissues in the embryo as well as to guide neuronal positioning and differentiation along the dorsoventral axis of the neural tube.

Glia limitans Thin astrocyte membrane surrounding the brain and spinal cord

The glia limitans, or the glial limiting membrane, is a thin barrier of astrocyte foot processes associated with the parenchymal basal lamina surrounding the brain and spinal cord. It is the outermost layer of neural tissue, and among its responsibilities is the prevention of the over migration of neurons and neuroglia, the supporting cells of the nervous system, into the meninges. The glia limitans also plays an important role in regulating the movement of small molecules and cells into the brain tissue by working in concert with other components of the central nervous system (CNS) such as the blood–brain barrier (BBB).

Satellite glial cell

Satellite glial cells(or satellite cells) are glial cells that cover the surface of neuron cell bodies in ganglia of the peripheral nervous system. Thus, they are found in sensory, sympathetic, and parasympathetic ganglia. Both satellite glial cells (SGCs) and Schwann cells are derived from the neural crest of the embryo during development. SGCs have been found to play a variety of roles, including control over the microenvironment of sympathetic ganglia. They are thought to have a similar role to astrocytes in the central nervous system (CNS). They supply nutrients to the surrounding neurons and also have some structural function. Satellite cells also act as protective, cushioning cells. Additionally, they express a variety of receptors that allow for a range of interactions with neuroactive chemicals. Many of these receptors and other ion channels have recently been implicated in health issues including chronic pain and herpes simplex. There is much more to be learned about these cells, and research surrounding additional properties and roles of the SGCs is ongoing.

Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.

A nerve guidance conduit is an artificial means of guiding axonal regrowth to facilitate nerve regeneration and is one of several clinical treatments for nerve injuries. When direct suturing of the two stumps of a severed nerve cannot be accomplished without tension, the standard clinical treatment for peripheral nerve injuries is autologous nerve grafting. Due to the limited availability of donor tissue and functional recovery in autologous nerve grafting, neural tissue engineering research has focused on the development of bioartificial nerve guidance conduits as an alternative treatment, especially for large defects. Similar techniques are also being explored for nerve repair in the spinal cord but nerve regeneration in the central nervous system poses a greater challenge because its axons do not regenerate appreciably in their native environment.

Glial scar Mass formed in response to injury to the nervous system

Glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.

Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues. The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood–brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells. However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response. Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood–brain barrier.

Spinal cord injury research seeks new ways to cure or treat spinal cord injury in order to lessen the debilitating effects of the injury in the short or long term. There is no cure for SCI, and current treatments are mostly focused on spinal cord injury rehabilitation and management of the secondary effects of the condition. Two major areas of research include neuroprotection, ways to prevent damage to cells caused by biological processes that take place in the body after the insult, and neuroregeneration, regrowing or replacing damaged neural circuits.

References

  1. 1 2 3 Ramón-Cueto A, Avila J (June 1998). "Olfactory ensheathing glia: properties and function". Brain Research Bulletin. 46 (3): 175–87. doi:10.1016/s0361-9230(97)00463-2. PMID   9667810.
  2. ↑ Nocentini S, Reginensi D, Garcia S, Carulla P, Moreno-Flores MT, Wandosell F, et al. (May 2012). "Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell tracking and traction force microscopy". Cellular and Molecular Life Sciences. 69 (10): 1689–703. doi:10.1007/s00018-011-0893-1. hdl: 2445/36438 . PMID   22205212.
  3. 1 2 3 4 5 6 Silva NA, Cooke MJ, Tam RY, Sousa N, Salgado AJ, Reis RL, Shoichet MS (September 2012). "The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate". Biomaterials. 33 (27): 6345–54. doi:10.1016/j.biomaterials.2012.05.050. hdl: 1822/20032 . PMID   22698724.
  4. 1 2 3 Ruitenberg MJ, Vukovic J, Sarich J, Busfield SJ, Plant GW (March–April 2006). "Olfactory ensheathing cells: characteristics, genetic engineering, and therapeutic potential". Journal of Neurotrauma. 23 (3–4): 468–78. doi:10.1089/neu.2006.23.468. PMID   16629630.
  5. ↑ Chehrehasa F, Ekberg JA, Lineburg K, Amaya D, Mackay-Sim A, St John JA (February 2012). "Two phases of replacement replenish the olfactory ensheathing cell population after injury in postnatal mice". Glia. 60 (2): 322–32. doi:10.1002/glia.22267. hdl: 10072/45582 . PMID   22065423.
  6. ↑ Windus LC, Lineburg KE, Scott SE, Claxton C, Mackay-Sim A, Key B, St John JA (May 2010). "Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions". Cellular and Molecular Life Sciences. 67 (10): 1735–50. doi:10.1007/s00018-010-0280-3. PMID   20143249.
  7. ↑ Quinn B (21 October 2014). "Paralysed man Darek Fidyka walks again after pioneering surgery". The Guardian . Retrieved 14 February 2015. [Fidyka], who is believed to be the first person in the world to recover from complete severing of the spinal nerves, can now walk with a frame and has been able to resume an independent life, even to the extent of driving a car, while sensation has returned to his lower limbs.
  8. ↑ "Paralysed man walks again after cell treatment". BBC. 21 October 2014. Retrieved 14 February 2015.
  9. 1 2 Harberts E, Yao K, Wohler JE, Maric D, Ohayon J, Henkin R, Jacobson S (August 2011). "Human herpesvirus-6 entry into the central nervous system through the olfactory pathway". Proceedings of the National Academy of Sciences of the United States of America. 108 (33): 13734–9. Bibcode:2011PNAS..10813734H. doi:10.1073/pnas.1105143108. PMC   3158203 . PMID   21825120.
  10. ↑ Liu C, Zheng Z, Gao R, Zhang K, Zhang L, Zhang L, Zhang L, Wei S, Kuang N, Song Y (2008). "Influence of olfactory ensheathing cell transplantation on body temperature of patients with old spinal cord injury". Neural Regeneration Research. 3 (7): 805–808.
  11. 1 2 Pessach I, Shimoni A, Nagler A (November 2012). "Apoptotic cells in allogeneic hematopoietic stem cell transplantations: "turning trash into gold"". Leukemia & Lymphoma. 53 (11): 2130–5. doi:10.3109/10428194.2012.690099. PMID   22553946.
  12. 1 2 Cassiani-Ingoni R, Greenstone HL, Donati D, Fogdell-Hahn A, Martinelli E, Refai D, et al. (November 2005). "CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell-cell fusion". Glia. 52 (3): 252–8. doi:10.1002/glia.20219. PMID   15920733.
  13. 1 2 3 4 Sandvig I, Hoang L, Sardella TC, Barnett SC, Brekken C, Tvedt K, et al. (2012). "Labelling of olfactory ensheathing cells with micron-sized particles of iron oxide and detection by MRI". Contrast Media & Molecular Imaging. 7 (4): 403–10. doi:10.1002/cmmi.1465. hdl: 11250/2623054 . PMID   22649046.
  14. ↑ Honoré A, Le Corre S, Derambure C, Normand R, Duclos C, Boyer O, et al. (March 2012). "Isolation, characterization, and genetic profiling of subpopulations of olfactory ensheathing cells from the olfactory bulb". Glia. 60 (3): 404–13. doi:10.1002/glia.22274. PMID   22161947.
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