scholarly journals Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 811 ◽  
Author(s):  
Yana Mukhamedshina ◽  
Iliya Shulman ◽  
Sergei Ogurcov ◽  
Alexander Kostennikov ◽  
Elena Zakirova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Comparative Study ◽  
Marked Change ◽  
Large Animal ◽  
Fibrin Matrix ◽  
Large Animal Models ◽  
Cord Injury ◽  
Post Traumatic ◽  
Spinal Contusion ◽  
Astroglial Activation

Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

scholarly journals Mesenchymal stem cells therapy for spinal cord contusion: a comparative study on small and large animal models

2019 ◽  
Author(s):  
Yana Mukhamedshina ◽  
Iliya Shulman ◽  
Sergei Ogurcov ◽  
Alexander Kostennikov ◽  
Lena Zakirova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Comparative Study ◽  
Large Animal ◽  
Fibrin Matrix ◽  
Cord Injury ◽  
Post Traumatic ◽  
Spinal Contusion ◽  
Astroglial Activation

AbstractHere, we provided a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix in a small (rat) and large (pig) spinal cord injury (SCI) model during sub-acute period of spinal contusion. Results of behavioral, electrophysiological, histological assessment, as well as results of immunohistochemistry and RT-PCR analysis suggest that application of AD-MSCs combined with a fibrin matrix in a subacute period in rats (2 weeks after injury) provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in (1) restoration of locomotor activity and conduction along spinal axons, (2) reduction of post-traumatic cavitation and enhancing tissue retention, and (3) modulation of microglial and astroglial activation. The effect of therapy with an autologous application of AD-MSCs was also confirmed in subacute period after spinal contusion in pigs (6 weeks after injury), however, with only partial replication of the findings observed in rats, i.e. (1) partial restoration of the somatosensory spinal pathways, (2) reduction of post-traumatic cavitation and enhancing tissue retention, and (3) modulation of astroglial activation in dorsal root entry zone. The results of this study suggest that application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

The Hemisection Approach in Large Animal Models of Spinal Cord Injury: Overview of Methods and Applications

2018 ◽  
Vol 33 (3) ◽  
pp. 240-251
Author(s):  
S. Wilson ◽  
S. J. Nagel ◽  
L. A. Frizon ◽  
D. C. Fredericks ◽  
N. A. DeVries-Watson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Animal Models ◽  
Large Animal ◽  
Large Animal Models ◽  
Cord Injury

scholarly journals Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment

2020 ◽  
Vol 21 (23) ◽  
pp. 8896
Author(s):  
Rustem Islamov ◽  
Farid Bashirov ◽  
Filip Fadeev ◽  
Roman Shevchenko ◽  
Andrei Izmailov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Combined Treatment ◽  
Small Sample ◽  
Functional Restoration ◽  
Synaptic Proteins ◽  
Large Animal ◽  
Cord Injury ◽  
Spinal Contusion

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

scholarly journals How to generate graded spinal cord injuries in swine?: Tools and procedures

2021 ◽  
Author(s):  
Mark Züchner ◽  
Manuel J. Escalona ◽  
Lena Hammerlund Teige ◽  
Evangelos Balafas ◽  
Lili Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Animal Models ◽  
Functional Outcome ◽  
Spinal Cord Injuries ◽  
Large Body ◽  
Swine Model ◽  
Large Animal ◽  
Large Animal Models ◽  
Cord Injury ◽  
The Impact

Spinal cord injury (SCI) is a medically, psychologically and socially disabling condition. A large body of our knowledge on the basic mechanisms of SCI has been gathered in rodents. For preclinical validation of promising therapies, the use of animal models that are closer to humans has several advantages. This has promoted a more intensive development of large animal models for SCI during the past decade. We have recently developed a multimodal SCI apparatus for large animals that generated biomechanically reproducible impacts in vivo. It is composed of a spring-load impactor and support systems for the spinal cord and the vertebral column. We now present the functional outcome of farm pigs and minipigs injured with different lesion strengths. There was a correlation between the biomechanical characteristics of the impact, the functional outcome, and the tissue damage observed several weeks after injury. We also provide a detailed description of the procedure to generate such a SCI in both farm pigs and minipigs, in the hope to ease the adoption of the swine model by other research groups.

A Review of Stem Cell Therapy for Spinal Cord Injury: Large Animal Models and the Frontier in Humans

2017 ◽  
Vol 98 ◽  
pp. 438-443 ◽  
Author(s):  
Brandon C. Gabel ◽  
Erik I. Curtis ◽  
Martin Marsala ◽  
Joseph D. Ciacci
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Animal Models ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Large Animal ◽  
Large Animal Models ◽  
Cord Injury

"Efficacy of Cognitive Behavioral Therapy in Post-traumatic Stress Disorder Among Spinal Cord Injury Patients: A Randomized Controlled Pilot Study"

2021 ◽  
Vol 21 (2) ◽  
pp. 143-162
Author(s):  
Anwar Khan ◽  
Faseeh Ullah ◽  
Omer Abid ◽  
Khizra Hafeez Awan
Keyword(s):  
Spinal Cord ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Behavioral Therapy ◽  
Ptsd Symptoms ◽  
Post Traumatic Stress ◽  
Randomized Controlled ◽  
Cord Injury ◽  
Post Traumatic

"Post-Traumatic Stress Disorder (PTSD) develops after exposure to or witnessing traumatic events. PTSD is very common among the Spinal Cord Injury (SCI) patients. PTSD can be successfully treated with the Cognitive Behavioral Therapy (CBT). However, CBT is mostly used in the western countries, so its efficacy in the eastern culture is still not fully known. Keeping this in view, the current study has determined the efficacy of CBT in the treatment of PTSD among the SCI patients in Pakistan. Using a Randomized Controlled Pilot Study design, data were collected through the Clinician-Administered PTSD Scale for DSM-5 from thirty patients admitted to the Paraplegic Center. Trauma-focused CBT(TF-CBT) protocol was applied through fourteen sessions. Data were analyzed by descriptive and multivariate statistics. Findings show that the level of PTSD symptoms gradually decreased from high at baseline (CAPS-5 Mean Scores μ= 3.6) to low during follow-up stage (CAPS-5 Mean Scores μ= 0.89). Results obtained from the present study on the efficacy of CBT are in concurrence with the research findings in other countries. This study supports the efficiency CBT intervention among Pakistani patients who had developed PTSD symptoms after suffering from SCI. Therefore, CBT can be widely used in the management of PTSD in Pakistan."

Numerical Investigation of Spinal Cord Injury After Flexion-Distraction Injuries At the Cervical Spine

2021 ◽  
Author(s):  
Marie-Helene Beausejour ◽  
Eric Wagnac ◽  
Pierre-Jean Arnoux ◽  
Jean-Marc Mac-Thiong ◽  
Yvan Petit
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cervical Spine ◽  
White Matter ◽  
Cervical Spinal Cord ◽  
Element Model ◽  
Von Mises Stress ◽  
Study Objective ◽  
Cord Injury ◽  
Post Traumatic

Abstract Flexion-distraction injuries frequently cause traumatic cervical spinal cord injury (SCI). Post-traumatic instability can cause aggravation of the secondary SCI during patient's care. However, there is little information on how the pattern of disco-ligamentous injury affects the SCI severity and mechanism. This study objective was to analyze how different flexion-distraction disco-ligamentous injuries affect the SCI mechanisms during post-traumatic flexion and extension. A cervical spine finite element model including the spinal cord was used and different combinations of partial or complete intervertebral disc (IVD) rupture and disruption of various posterior ligaments were modeled at C4-C5, C5-C6 or C6-C7. In flexion, complete IVD rupture combined with posterior ligamentous complex rupture was the most severe injury leading to the most extreme von Mises stress (47 to 66 kPa), principal strains p1 (0.32 to 0.41 in white matter) and p3 (-0.78 to -0.96 in white matter) in the spinal cord and to the most important spinal cord compression (35 to 48 %). The main post-trauma SCI mechanism was identified as compression of the anterior white matter at the injured level combined with distraction of the posterior spinal cord during flexion. There was also a concentration of the maximum stresses in the gray matter after injury. Finally, in extension, the injuries tested had little impact on the spinal cord. The capsular ligament was the most important structure in protecting the spinal cord. Its status should be carefully examined during patient's management.

scholarly journals Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

2019 ◽  
Vol 126 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Breathing Patterns ◽  
Cord Injury ◽  
Spinal Contusion ◽  
Cervical Spinal Injury

The present study was designed to investigate breathing patterns across the sleep-wake state following a high cervical spinal injury in rats. The breathing patterns (e.g., respiratory frequency, tidal volume, and minute ventilation), neck electromyogram, and electroencephalography of unanesthetized adult male rats were measured at the acute (i.e., 1 day), subchronic (i.e., 2 wk), and/or chronic (i.e., 6 wk) injured stages after unilateral contusion of the second cervical spinal cord. Cervical spinal cord injury caused a long-term reduction in the tidal volume but did not influence the sleep-wake cycle duration. The minute ventilation during sleep was usually lower than that during the wake period in uninjured animals due to a decrease in respiratory frequency. However, this sleep-induced reduction in respiratory frequency was not observed in contused animals at the acute injured stage. By contrast, the tidal volume was significantly lower during sleep in contused animals but not uninjured animals from the acute to the chronic injured stage. Moreover, the frequency of sigh and postsigh apnea was elevated in acutely contused animals. These results indicated that high cervical spinal contusion is associated with exacerbated sleep-induced attenuation of the tidal volume and higher occurrence of sleep apnea, which may be detrimental to respiratory functional recovery after cervical spinal cord injury. NEW & NOTEWORTHY Cervical spinal injury is usually associated with sleep-disordered breathing. The present study investigated breathing patterns across sleep-wake state following cervical spinal injury in the rat. Unilateral cervical spinal contusion significantly impacted sleep-induced alteration of breathing patterns, showing a blunted frequency response and exacerbated attenuated tidal volume and occurrence of sleep apnea. The result enables us to investigate effects of cervical spinal injury on the pathogenesis of sleep-disordered breathing and evaluate potential therapies to improve respiration.

Sign in / Sign up

Export Citation Format

Share Document