Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

Takeoka, Aya; Jindrich, Devin L.; Muñoz-Quiles, Cintia; Zhong, Hui; Brand, Rubia van den; Pham, Dániel; Ziegler, Matthias; Ramón‐Cueto, Almudena; Roy, Roland R.; Edgerton, V. Reggie; Phelps, Patricia E.

doi:10.1523/jneurosci.4967-10.2011

Cited by 61 publications

(55 citation statements)

References 64 publications

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“…Retrograde targeting methods would be one means of achieving cell-specific neuronal growth factor expression (Fortun et al, 2009; Hollis et al, 2010), but the challenge of limiting growth factor expression to sub-regions of the dendritic tree would be substantially more difficult. Third, axonal regeneration may require interaction with specific rehabilitation strategies (García-Alías et al, 2009; Takeoka et al, 2011), approaches that will be tested in future studies.…”

Section: Discussionmentioning

confidence: 99%

Motor Axonal Regeneration after Partial and Complete Spinal Cord Transection

Blesch²,

Graham³

et al. 2012

Journal of Neuroscience

127

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We subjected rats to either partial mid-cervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor (BDNF) gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared to several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair, and the need for additional control and shaping of axonal regeneration.

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Section: Discussionmentioning

confidence: 99%

Motor Axonal Regeneration after Partial and Complete Spinal Cord Transection

Blesch²,

Graham³

et al. 2012

Journal of Neuroscience

127

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“…In humans, a phase I clinical trial of spinal cord injury repair demonstrated that transplantation of autologous OECs is feasible and safe [73,74]. In preclinical animal trials, it has been shown that transplanted OECs can survive and migrate within the injured spinal cord of rats [16,75], reduce scar and cavity formation [76,77], lead to improved functional locomotor and hindlimb recovery [78,79] and can restore breathing and climbing ability [80] even after complete transection of the spinal cord [79,81]. Similarly, Schwann cells have been shown to promote axon growth in spinal injury models [82] although they are not always as effective as OECs [83].…”

Section: Why Are Oecs Suitable For Neural Repair Therapies?mentioning

confidence: 99%

The Migration of Olfactory Ensheathing Cells during Development and Regeneration

Ekberg¹,

Amaya²,

Mackay‐Sim³

et al. 2012

Neurosignals

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The primary olfactory nervous system is unique in that it continuously renews itself and regenerates after injury. These properties are attributed to the presence of olfactory glia, termed olfactory ensheathing cells (OECs). Evidence is now emerging that individual OEC populations exist with distinct anatomical localisations and physiological properties, but their differential roles have not been determined. Unlike other glia, OECs can migrate from the periphery into the central nervous system, and organised OEC migration can enhance axonal extension after injury. Despite this, the mechanisms regulating OEC migration are largely unknown. Here, we provide an overview of the roles of OECs in development and adulthood. We review the latest research describing the differences between individual OEC subpopulations and discuss potential regulatory mechanisms for OEC guidance and migration. Using advanced time lapse techniques, we have obtained novel insights into how OECs behave in a complex multicellular environment which we discuss here with particular focus on cell-cell interactions. Significantly, transplantation of OECs constitutes a promising novel therapy for nerve injuries, but results are highly variable and the method needs improvement. We here review the roles of transplanted OECs in neural repair of damaged neuronal tracts distinct from the primary olfactory nervous system.

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“…An exception may be the use of olfactory ensheathing cells (OECs), that surround the axons of the sensory neurons both in the olfactory epithelium and as they grow into the olfactory bulb. The OECs have been proposed to ameliorate function following spinal cord injury and nerve root avulsion in rodents [48][49][50][51]. In recent Phase I clinical trials, patients with spinal injury were transplanted with OEC grown from their nasal mucosa.…”

Section: Sources Of Somatic Stem Cells For Autologous Therapiesmentioning

confidence: 99%

Autologous stem cells for personalised medicine

Prasongchean¹,

Ferretti²

2012

New Biotechnology

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Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention.

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Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

Cited by 61 publications

References 64 publications

Motor Axonal Regeneration after Partial and Complete Spinal Cord Transection

Motor Axonal Regeneration after Partial and Complete Spinal Cord Transection

The Migration of Olfactory Ensheathing Cells during Development and Regeneration

Autologous stem cells for personalised medicine

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