Restoration of Hand Function In a Rat Model of Repair of Brachial Plexus Injury (original) (raw)

Motor recovery following olfactory ensheathing cell transplantation in rats with spinal cord injury

Neurology India, 2011

Background: Olfactory ensheathing cells (OEC) are considered to be the most suitable cells for transplantation therapy in the central nervous system (CNS) because of their unique ability to help axonal regrowth and remyelination in the CNS. However, there are conflicting reports about the success rates with OEC. Aim: This study was undertaken to evaluate the therapeutic effect of OEC in rat models using different cell dosages. Material and Methods: OECs harvested from the olfactory mucosa of adult white Albino rats were cultured. Spinal cord injury (SCI) was inflicted at the lower thoracic segment in a control and test group of rats. Two weeks later, OECs were delivered in and around the injured spinal cord segment of the test group of the rats. The outcome in terms of locomotor recovery of limb muscles was assessed on a standard rating scale and by recording the motor-evoked potentials from the muscles during transcranial electrical stimulation. Finally, the animals were sacrificed to assess the structural repair by light microscopy. Statistical Analysis: Wilcoxon signed rank test and Mann-Whitney U-test were used to compare the data in the control and the test group of animals. A P value of <0.05 was considered significant. Results: The study showed a moderate but significant recovery of the injured rats after OEC transplantation (P=0.005). Conclusion: Transplantation of OECs along with olfactory nerve fibroblasts improved the motor recovery in rat models with SCI.

Olfactory ensheathing cells promote collateral axonal branching in the injured adult rat spinal cord

2004

In recent years, injection of olfactory ensheathing cells (ECs) into the spinal cord has been used as an experimental strategy to promote regeneration of injured axons. In this study, we have compared the effects of transplanting encapsulated ECs with those injected directly into the spinal cord. The dorsal columns of adult rats were cut at T 8 -9 and rats in experimental groups received either EC-filled porous polymer capsules or culture medium (CM)-filled capsules with ECs injected at the injury site. Control rats were in three groups: (1) uninjured, (2) lesion with transplantation of CM-filled capsules and (3) lesion with transplantation of CM-filled capsules and injections of CM. Three weeks after injury, Fluororuby was injected into the hindlimb motor and somatosensory cortex to label corticospinal neurons. Observations indicated that there were a few regenerating fibres, up to 10, in the EC-treated groups. In rats that received encapsulated ECs, regenerating fibres were present in close association with the capsule. Rats that received EC injections demonstrated a significant increase in the number of collateral branches from the intact ventral corticospinal tract (vCST) compared with the corresponding control, CM-injected group ( P = 0.003), while a trend for increased collateral branches was observed in rats that received encapsulated ECs ( P = 0.07).

Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat

Glia, 2007

The goal of this study was to ascertain whether olfactory ensheathing cells (OECs) were able to promote axonal regeneration and functional recovery when transplanted 45 days after complete transection of the thoracic spinal cord in adult rats. OECs promoted partial restitution of supraspinal pathways evaluated by motor evoked potentials and modest recovery of hindlimb movements. In addition, OEC grafts reduced lumbar reflex hyperexcitability from the first month after transplantation. Histological results revealed that OECs facilitated corticospinal and raphespinal axons regrowth through the injury site and into the caudal spinal cord segments. Interestingly, raphespinal but not corticospinal fibers regenerated long distances through the gray matter and reached the lower lumbar segments (L5) of the spinal cord. However, delayed OEC grafts failed to reduce posttraumatic astrogliosis. In conclusion, the beneficial effects found in the present study further support the use of OECs for treating chronic spinal cord injuries.

Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

Glia, 2003

We studied the effects of olfactory ensheathing cells (OECs) transplanted in a photochemical spinal cord injury in adult rats. After dorsal laminectomy at T8 vertebra, subjacent spinal cord was bathed with rose Bengal for 10 min and illuminated with visible light by means of an optic fiber connected to a halogen lamp for 2.5 min at maximal intensity of 8 kLux. Eight injured rats received a suspension of OECs in DMEM, and another eight rats received DMEM alone. Locomotor ability scored by the BBB scale, pain sensibility by the plantar algesimetry test, and motor-and somatosensory-evoked potentials by electrophysiological techniques were evaluated for 3 months postsurgery. Finally, all rats were perfused with paraformaldehyde and transverse sections from the spinal cord segment at the lesion site were immunostained against GFAP. Area of the preserved spinal cord parenchyma was measured from the GFAPimmunolabeled cord sections. The BBB score and the amplitude of motor-and somatosensory-evoked potentials were higher in OECs-transplanted rats than in DMEMinjected animals throughout follow-up, whereas the withdrawal response to heat noxious stimulus was lower in OEC-than in DMEM-injected rats. The area of preserved spinal cord was significantly larger in OECs-transplanted rats than in DMEM-injected animals. These results indicate that OECs promote functional and morphological preservation of the spinal cord after photochemical injury. GLIA 42: [275][276][277][278][279][280][281][282][283][284][285][286] 2003.

Repair of spinal cord injury by co-transplantation of embryonic stem cell-derived motor neuron and olfactory ensheathing cell

Iranian biomedical journal, 2009

The failure of regeneration after spinal cord injury (SCI) has been attributed to axonal demyelination and neuronal death. Cellular replacement and white matter regeneration are both necessary for SCI repair. In this study, we evaluated the co-transplantation of olfactory ensheathing cells (OEC) and embryonic stem (ES) cell-derived motor neurons (ESMN) on contused SCI. OEC cultured from olfactory nerve rootlets and olfactory bulbs. ESMN was generated by exposing mouse ES cells to retinoic acid and sonic hedgehog. Thirty female rats were used to prepare SCI models in five groups. Control and medium-injected groups was subjected to induce lesion without cell transplantation. OEC or ESMN or both were transplanted into the site of the lesion in other groups. The purity of OEC culture was 95%. Motor neuron progenitor markers (Olig2, Nkx6.1 and Pax6) and motor neuron markers (Isl1, Isl2 and Hb9) were expressed. Histological analysis showed that significantly more (P<0.001) spinal tissu...

Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging

Cell transplantation, 2014

Treatment of patients sustaining a complete spinal cord injury remains an unsolved clinical problem because of the lack of spontaneous regeneration of injured central axons. A 38-year-old man sustained traumatic transection of the thoracic spinal cord at upper vertebral level Th9. At 21 months after injury, the patient presented symptoms of a clinically complete spinal cord injury (American Spinal Injury Association class A-ASIA A). One of the patient's olfactory bulbs was removed and used to derive a culture containing olfactory ensheathing cells and olfactory nerve fibroblasts. Following resection of the glial scar, the cultured cells were transplanted into the spinal cord stumps above and below the injury and the 8-mm gap bridged by four strips of autologous sural nerve. The patient underwent an intense pre- and postoperative neurorehabilitation program. No adverse effects were seen at 19 months postoperatively, and unexpectedly, the removal of the olfactory bulb did not lead...

Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells

Glia, 2006

Transplantation of olfactory ensheathing cells (OECs) into the damaged rat spinal cord leads to directed elongative axonal regeneration and improved functional outcome. OECs are known to produce a number of neurotrophic molecules. To explore the possibility that OECs are neuroprotective for injured corticospinal tract (CST) neurons, we transplanted OECs into the dorsal transected spinal cord (T9) and examined primary motor cortex (M1) to assess apoptosis and neuronal loss at 1 and 4 weeks post-transplantation. The number of apoptotic cortical neurons was reduced at 1 week, and the extent of neuronal loss was reduced at 4 weeks. Biochemical analysis indicated an increase in BDNF levels in the spinal cord injury zone after OEC transplantation at 1 week. The transplanted OECs associated longitudinally with axons at 4 weeks. Thus, OEC transplantation into the injured spinal cord has distant neuroprotective effects on descending cortical projection neurons.

Undesired effects of a combinatorial treatment for spinal cord injury – transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus

European Journal of Neuroscience, 2008

Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration‐associated genes. Cell body treatment with brain‐derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration‐associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a c...

Functional recovery not correlated with axon regeneration through olfactory ensheathing cell-seeded scaffolds in a model of acute spinal cord injury

Tissue Engineering and Regenerative Medicine, 2016

Traumatically injured central nervous system (CNS) forms a hostile environment to axon regeneration and repair via cell and tissue destruction caused by the initial insult, followed by a cascade of secondary pathophysiological events including the increased expression of certain axon growth-repulsive chondroitin sulphate proteoglycans during scarring, the presence of myelin debris and the formation of cystic cavitation [1-3]. Many studies have shown that CNS axon regeneration can take place after traumatic injury provided that an appropriate growth-promoting substrate has been implanted into the lesion site [4]. Cell transplantation-based repair strategies have demonstrated the implantation of donor cells to be an effective means for importing growth promoting factors/substrates into lesioned tissues. A number of cell types, including neural and non-neural stem cells, neural progenitors, Schwann cells (SC), astrocytes, oligodendrocytes, olfactory ensheathing cells (OECs) and activated macrophages have, so far, been investigated in experimen

Subarachnoid Space Transplantation of Schwann and/or Olfactory Ensheathing Cells Following Severe Spinal Cord Injury Fails to Improve Locomotor Recovery in Rats

Acta medica Iranica, 2016

Treatment of spinal cord injury by exogenous cells has brought both successful and unsuccessful results. Olfactory ensheathing cells and Schwann cells have been widely used for transplantation purposes. In this study, we investigated the effects of these cells on contused spinal cord by introducing cells into subarachnoid space. Fifty thousand Schwann cells or olfactory ensheathing cells or a mixture of both cell types were transplanted one week after a 3-second clip compression injury at T-9 spinal cord level in rats. Starting from the day one of spinal cord injury, animals were assessed for six months by BBB test and then were sacrificed for immunohistochemistry labeling of the spinal cord injury site. There was no locomotor recovery in any of the treatment groups including controls. Immunohistochemistry assessment indicated positive labeling of P75 and S100 markers in the cell-transplanted groups compared with control. Our data suggest that transplantation of Schwann cells and/or...