scholarly journals Transplantation of Cultured Olfactory Bulb Cells Prevents Abnormal Sensory Responses during Recovery from Dorsal Root Avulsion in the Rat

2017 ◽  
Vol 26 (5) ◽  
pp. 913-924 ◽  
Author(s):  
Andrew Collins ◽  
Daqing Li ◽  
Stephen B. Mcmahon ◽  
Geoffrey Raisman ◽  
Ying Li

The central branches of the C7 and C8 dorsal roots were avulsed close to their entry point into the spinal cord in adult rats. The forepaw responses to heat and cold stimuli were tested at 1, 2, and 3 weeks after injury. Over this period, the paws were sensitive to both stimuli at 1-2 weeks and returned toward normal at 3 weeks. Immunohistology showed no evidence of axonal regeneration into the spinal cord in a control group of rats with avulsion only, implying that adjacent dorsal roots and their corresponding dermatomes were involved in the recovery. In a further group of rats, a mixture of bulbar olfactory ensheathing cells and olfactory nerve fibroblasts were transplanted into the gap between the avulsed roots and the spinal cord at the time of avulsion. These rats showed no evidence of either loss of sensation or exaggerated responses to stimuli at any of the time points from 1 to 3 weeks. Immunohistology showed that the transplanted cells formed a complete bridge, and the central branches of the dorsal root fibers had regenerated into the dorsal horn of the spinal cord. These regenerating axons, including Tuj1 and CGRP immunoreactive fibers, were ensheathed by the olfactory ensheathing cells. This confirms our previous demonstration of central regeneration by these transplants and suggests that such transplants may provide a useful means to prevent the development of abnormal sensations such as allodynia after spinal root lesions.

2004 ◽  
Vol 1 (3) ◽  
pp. 201-209 ◽  
Author(s):  
RUBèN LóPEZ-VALES ◽  
GUILLERMO GARCíA-ALíAS ◽  
JOAQUIM FORéS ◽  
JOSé M. VELA ◽  
XAVIER NAVARRO ◽  
...  

Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to exert neuroprotective effects and promote functional recovery. In the present study, we investigated the potential modulatory effects of OECs on the inflammatory reaction developed after photochemical injury to the spinal cord. OEC cultures were obtained from olfactory bulbs of adult Sprague-Dawley rats. Photochemical spinal cord injury was induced in adult rats at T8. Thirty minutes after the insult, either a suspension of OECs (180 000 cells in 12 µl DMEM) or DMEM alone was injected into the lesioned spinal cord. At 3, 7 and 14 days post-operation (dpo), five animals from each group were processed for histology. Double-fluorescent labeling of transverse sections of the cord were made by combination of immunohistochemistry for inflammatory markers, interleukin 1β (IL-1β) and inducible nitric oxide synthase (iNOS), and for selective markers of astrocytes (glial fibrillar acidic protein; GFAP) and microglia/macrophages (tomato lectin; LEC). Differences in the intensity and time course of glial response, and IL-1β and iNOS expression were found between the two groups of rats. The reactivity grade against IL-1β, iNOS, GFAP and LEC in OEC-transplanted rats was higher at 7 dpo and lower at 14 dpo compared with DMEM-injected rats. These results indicate that the mechanisms underlying neuroprotection by OECs might be caused by earlier, higher and shorter duration of microglia/macrophage and astrocyte responses after injury.


2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 132S-159S ◽  
Author(s):  
Ronak Reshamwala ◽  
Megha Shah ◽  
James St John ◽  
Jenny Ekberg

Olfactory ensheathing cells (OECs), the glial cells of the primary olfactory nervous system, support the natural regeneration of the olfactory nerve that occurs throughout life. OECs thus exhibit unique properties supporting neuronal survival and growth. Transplantation of OECs is emerging as a promising treatment for spinal cord injury; however, outcomes in both animals and humans are variable and the method needs improvement and standardization. A major reason for the discrepancy in functional outcomes is the variability in survival and integration of the transplanted cells, key factors for successful spinal cord regeneration. Here, we review the outcomes of OEC transplantation in rodent models over the last 10 years, with a focus on survival and integration of the transplanted cells. We identify the key factors influencing OEC survival: injury type, source of transplanted cells, co-transplantation with other cell types, number and concentration of cells, method of delivery, and time of transplantation after the injury. We found that two key issues are hampering optimization and standardization of OEC transplantation: lack of (1) reliable methods for identifying transplanted cells, and (2) three-dimensional systems for OEC delivery. To develop OEC transplantation as a successful and standardized therapy for spinal cord injury, we must address these issues and increase our understanding of the complex parameters influencing OEC survival.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Shifeng Wu ◽  
Guanqun Cui ◽  
Hua Shao ◽  
Zhongjun Du ◽  
Jack C. Ng ◽  
...  

The mechanisms behind the repairing effects of the cotransplantation of olfactory ensheathing cells (OECs) with bone marrow mesenchymal stromal cells (BMSCs) have not been fully understood. Therefore, we investigated the effects of the cotransplantation of OECs with BMSCs on antiapoptotic effects in adult rats for which the models of SCI are induced. We examined the changes in body weight, histopathological changes, apoptosis, and the expressions of apoptosis-related proteins after 14 days and 28 days after transplantation. We also assessed animal locomotion using BBB test. We found that treatment with OECs and BMSCs had a remissive effect on behavioral outcome and histopathological changes induced SCI. Furthermore, we observed the significant antiapoptotic effect on cotransplant treated group. In addition, cotransplantation of OECs with BMSCs was found to have more significant repairing effect than that of OECs or BMSCs alone. Furthermore, the recovery of hind limb could be related to antiapoptotic effect of OECs and BMSCs through downregulating the apoptotic pathways. Finally, our data suggested the cotransplantation of OECs with BMSCs holds promise for a potential cure after SCI through the ability to incorporate into the spinal cord.


2019 ◽  
Vol 28 (9-10) ◽  
pp. 1212-1219 ◽  
Author(s):  
Andrew Collins ◽  
Ahmed Ibrahim ◽  
Daqing Li ◽  
Modinat Liadi ◽  
Ying Li

The dorsal root entry zone is often used in research to examine the disconnection between the central and peripheral parts of the nervous system which occurs following injury. Our laboratory and others have used transplantation of olfactory ensheathing cells (OECs) to repair experimental spinal cord injuries. We have previously used a four dorsal root (C6–T1) transection model to show that transplantation of OECs can reinstate rat forelimb proprioception in a climbing task. Until now, however, we have not looked in detail at the anatomical interaction between OECs and the peripheral/central nervous system regions which form the transitional zone. In this study, we compared short- and long-term OEC survival and their interaction with the surrounding dorsal root tissue. We reveal how transplanted OECs orient toward the spinal cord and allow newly formed axons to travel across into the dorsal horn of the spinal cord. Reconstruction of the dorsal root entry zone was supported by OEC ensheathment of axons at the injured site and also at around 3 mm further away at the dorsal root ganglion. Quantitative analysis revealed no observable difference in dorsal column axonal loss between transplanted and control groups of rats.


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