scholarly journals Chemotactic TEG3 Cells’ Guiding Platforms Based on PLA Fibers Functionalized With the SDF-1α/CXCL12 Chemokine for Neural Regeneration Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Oscar Castaño ◽  
Ana López-Mengual ◽  
Diego Reginensi ◽  
Andreu Matamoros-Angles ◽  
Elisabeth Engel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Regeneration ◽  
Functional Improvement ◽  
Chemical Concentration ◽  
Olfactory Ensheathing Cell ◽  
Promising Therapeutic Approach ◽  
Cord Injury ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Inhibitory Molecules

(Following spinal cord injury, olfactory ensheathing cell (OEC) transplantation is a promising therapeutic approach in promoting functional improvement. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical concentration differences. Here we compare the attachment, morphology, and directionality of an OEC-derived cell line, TEG3 cells, seeded on functionalized nanoscale meshes of Poly(l/dl-lactic acid; PLA) nanofibers. The size of the nanofibers has a strong effect on TEG3 cell adhesion and migration, with the PLA nanofibers having a 950 nm diameter being the ones that show the best results. TEG3 cells are capable of adopting a bipolar morphology on 950 nm fiber surfaces, as well as a highly dynamic behavior in migratory terms. Finally, we observe that functionalized nanofibers, with a chemical concentration increment of SDF-1α/CXCL12, strongly enhance the migratory characteristics of TEG3 cells over inhibitory substrates.

scholarly journals The Potential for Cellular Therapy Combined with Growth Factors in Spinal Cord Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jack Rosner ◽  
Pablo Avalos ◽  
Frank Acosta ◽  
John Liu ◽  
Doniel Drazin
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Growth Factors ◽  
Cellular Therapy ◽  
Embryonic Stem ◽  
Neural Regeneration ◽  
Functional Improvement ◽  
Combination Therapies ◽  
Cord Injury

Any traumatic spinal cord injury (SCI) may cause symptoms ranging from pain to complete loss of motor and sensory functions below the level of the injury. Currently, there are over 2 million SCI patients worldwide. The cost of their necessary continuing care creates a burden for the patient, their families, and society. Presently, few SCI treatments are available and none have facilitated neural regeneration and/or significant functional improvement. Research is being conducted in the following areas: pathophysiology, cellular therapies (Schwann cells, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, olfactory ensheathing cells), growth factors (BDNF), inhibitory molecules (NG2, myelin protein), and combination therapies (cell grafts and neurotrophins, cotransplantation). Results are often limited because of the inhibitory environment created following the injury and the limited regenerative potential of the central nervous system. Therapies that show promise in small animal models may not transfer to nonhuman primates and humans. None of the research has resulted in remarkable improvement, but many areas show promise. Studies have suggested that a combination of therapies may enhance results and may be more effective than a single therapy. This paper reviews and discusses the most promising new SCI research including combination therapies.

scholarly journals Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

Neurosignals ◽  
2017 ◽  
Vol 25 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Changxing Wang ◽  
Chenglong Sun ◽  
Zhiying Hu ◽  
Xue Huo ◽  
Yang Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neural Regeneration ◽  
Olfactory Ensheathing Cell ◽  
Adult Rats ◽  
Cord Injury

scholarly journals Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 73
Author(s):  
Bilal El Waly ◽  
Vincent Escarrat ◽  
Jimena Perez-Sanchez ◽  
Jaspreet Kaur ◽  
Florence Pelletier ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Immune Cell ◽  
Two Photon ◽  
Sensory Axons ◽  
Promising Therapeutic Approach ◽  
Cord Injury ◽  
Biochemical Signals ◽  
Coated Carbon ◽  
Striking Effect

The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management.

First experience with chronic epidural spinal cord stimulation in Khanty-Mansi autonomous okrug — clinical observations

2021 ◽  
Vol LIII (2) ◽  
pp. 94-100
Author(s):  
Olga A. Bondarenko ◽  
Gaspar V. Gavrilov ◽  
Vadim A. Padurets ◽  
Roman V. Kasich
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
Pain Syndrome ◽  
Chronic Neuropathic Pain ◽  
Neuropathic Pain Syndrome ◽  
Epidural Stimulation ◽  
Cord Injury ◽  
Epidural Spinal Cord Stimulation ◽  
And Migration

Purpose of the work. The article is devoted to the first experience of epidural stimulation in the Khanty-Mansiysk Autonomous Okrug at the budgetary institution Surgut Clinical Trauma Hospital. Clinical examples are presented for two main indications for the application of this technique (disease of the operated spine, a consequence of spinal cord injury in combination with chronic neuropathic pain syndrome). Research methods. An assessment of the intensity of pain syndrome was given according to a visual analogue scale, the Pain Detect questionnaire; indicators of anxiety, depression on the HADS scale; quality of life according to the Oswestry questionnaire for a follow-up period of 6-12 months in patients with chronic epidural stimulation. Results. A positive assessment of the action during test neurostimulation was 63.3% (38 patients). Of the established permanent systems, a good result was achieved and persisted for 12 months or more in 96% (24 patients). It was necessary to change the stimulation parameters in 13% (3 patients). Revision of permanent systems was performed in 20% (5 patients), due to the progression of the degenerative-dystrophic process of the spine, damage and migration of system elements. Conclusions. Chronic epidural spinal cord stimulation has established itself as a personalized, highly effective, minimally invasive and safe method of treating chronic neuropathic pain syndromes. Multicomponent corrective action is of scientific interest and requires further study.

Epidural electrical stimulation to facilitate locomotor recovery after spinal cord injury

2021 ◽  
Author(s):  
Johannie Audet ◽  
Charly G. Lecomte
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Clinical Implementation ◽  
Preclinical Models ◽  
Lumbosacral Region ◽  
Locomotor Recovery ◽  
Promising Therapeutic Approach ◽  
Cord Injury ◽  
Stimulation Of

Tonic or phasic electrical epidural stimulation of the lumbosacral region of the spinal cord facilitates locomotion and standing in a variety of preclinical models with severe spinal cord injury. However, the mechanisms of epidural electrical stimulation that facilitate sensorimotor functions remain largely unknown. This review aims to address how epidural electrical stimulation interacts with spinal sensorimotor circuits and discusses the limitations that currently restrict the clinical implementation of this promising therapeutic approach.

scholarly journals Olfactory ensheathing cell transplantation for chronic spinal cord injury: A long-term follow-up study

2021 ◽  
Vol 9 (2) ◽  
pp. 94-105
Author(s):  
Naifeng Kuang ◽  
Xiaoyu Wang ◽  
Yuexia Chen ◽  
Guifeng Liu ◽  
Fan’e Kong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Autonomic Function ◽  
Spinal Injury ◽  
International Standards ◽  
Olfactory Ensheathing Cell ◽  
Cord Injury ◽  
Long Term Follow Up

Spinal cord injury is a serious disabling condition. Transplantation of olfactory ensheathing cells (OECs) is one of the most promising treatments for spinal cord injury (SCI). Thirty-nine patients with chronic SCI received OEC transplantation and completed long-term follow-up, with a minimum follow-up of 7 years. We assessed sensorimotor function with the American Spinal Injury Association (ASIA) Impairment Scale (AIS) and autonomic nervous function by the International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI), and sympathetic skin responses (SSR). The scores of each group were significantly higher after OECs transplantation than before treatment. SSR latencies were shorter and response amplitudes increased after treatment. Long-term follow-up showed further improvement only in motor function and autonomic function compared with 3 months postoperatively. No complications occurred in any patient during long-term follow-up. The results indicate that the transplantation of OECs in spinal cord restored function without serious side effects.

scholarly journals Subcutaneous granulocyte colony-stimulating factor administration for subacute traumatic spinal cord injuries, report of neurological and functional outcomes: a double-blind randomized controlled clinical trial

2019 ◽  
Vol 30 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Nazi Derakhshanrad ◽  
Hooshang Saberi ◽  
Mir Saeed Yekaninejad ◽  
Mohammad Taghi Joghataei
Keyword(s):  
Clinical Trial ◽  
Spinal Cord ◽  
Placebo Group ◽  
Spinal Cord Injuries ◽  
Functional Improvement ◽  
Granulocyte Colony Stimulating Factor ◽  
Double Blind ◽  
Cord Injury ◽  
The Mean ◽  
Stimulating Factor

OBJECTIVEGranulocyte-colony stimulating factor (G-CSF) is a major cytokine that has already been clinically verified for chronic traumatic spinal cord injuries (TSCIs). In this study, the authors set out to determine the safety and efficacy of G-CSF administration for neurological and functional improvement in subacute, incomplete TSCI.METHODSThis phase II/III, prospective, double-blind, placebo-controlled, parallel randomized clinical trial was performed in 60 eligible patients (30 treatment, 30 placebo). Patients with incomplete subacute TSCIs with American Spinal Injury Association Impairment Scale (AIS) grades B, C, and D were enrolled. Patients were assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, Spinal Cord Independence Measure (SCIM-III) and International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), just before intervention and at 1, 3, and 6 months, after 7 daily subcutaneous administrations of 300 μg/day of G-CSF in the treatment group and placebo in the control group.RESULTSAmong 60 participants, 28 patients (93.3%) in the G-CSF group and 26 patients (86.6%) in the placebo group completed the study protocol. After 6 months of follow-up, the AIS grade remained unchanged in the placebo group, while in the G-CSF group 5 patients (45.5%) improved from AIS grade B to C, 5 (45.5%) improved from AIS grade C to grade D, and 1 patient (16.7%) improved from AIS grade D to E. The mean ± SEM change in ISNCSCI motor score in the G-CSF group was 14.9 ± 2.6 points, which was significantly greater than in the placebo group (1.4 ± 0.34 points, p < 0.001). The mean ± SEM light-touch and pinprick sensory scores improved by 8.8 ± 1.9 and 10.7 ± 2.6 points in the G-CSF group, while those in the placebo group improved by 2.5 ± 0.60 and 1.2 ± 0.40 points, (p = 0.005 and 0.002, respectively). Evaluation of functional improvement according to the IANR-SCIFRS instrument revealed significantly more functional improvement in the G-CSF group (10.3 ± 1.3 points than in the placebo group (3.0 ± 0.81 points; p < 0.001). A significant difference was also observed between the 2 groups as measured by the SCIM-III instrument (29.6 ± 4.1 vs 10.3 ± 2.2, p < 0.001).CONCLUSIONSIncomplete subacute TSCI is associated with significant motor, sensory, and functional improvement after administration of G-CSF.Clinical trial registration no.: IRCT201407177441N3 (www.irct.ir)

scholarly journals Safety and Feasibility of Autologous Olfactory Ensheathing Cell and Bone Marrow Mesenchymal Stem Cell Co-transplantation in Chronic Human Spinal Cord Injury: A Clinical Trial

2021 ◽  
Author(s):  
Homa Zamani ◽  
Mina Soufizomorrod ◽  
Saeed Oraee-Yazdani ◽  
Dariush Naviafar ◽  
Mohammadhosein Akhlaghpasand ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Safety Issue ◽  
Functional Evaluation ◽  
Olfactory Ensheathing Cell ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Cell-based therapies are considered as promising strategies for spinal cord regeneration. However, a combinatorial cell therapeutic approach seems more beneficial as it can target various aspects of the injury. Here, we assessed the safety and feasibility of autologous mucosal Olfactory Ensheathing Cell (OEC) and bone marrow Mesenchymal Stem Cell (MSC) co-transplantation in patients with chronic, complete (American Spinal Injury Association (ASIA) classification A) Spinal Cord Injury (SCI). Three patients with the traumatic SCI of the thoracic level were enrolled. They received autologous OEC and MSC combination through the lumbar puncture. All adverse events and possible functional outcomes were documented performing pre- and post-operative general clinical examination, Magnetic Resonance Imaging (MRI), neurological assessment based on the International Standard of Neurological Classification for SCI (ISNCSCI), and functional evaluation using Spinal Cord Independence Measure version III (SCIM III). No serious safety issue was recorded during the two years of follow-up. MRI findings remained unchanged with no neoplastic tissue formation. ASIA impairment scale improved from A to B in one of the participants. SCIM III evaluation also showed some degrees of progress in this patient's quality of life. The two other patients had negligible or no improvement in their sensory scores without any changes in the ASIA impairment scale and SCIM III scores. No motor recovery was observed in any of the participants. Overall, this two-year trial was not associated with any adverse findings, which may suggest the safety of autologous OEC and bone marrow MSC combination for the treatment of human SCI.This study was registered at the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20160110025930N2/ registration date: 2018-09-29).

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