Lower-Limb Neuroprostheses

Author(s):  
Monzurul Alam ◽  
Jufang He

Regaining lower-limb functionality such as walking is one of the highest priorities among all the disabilities of paraplegics following Spinal Cord Injury (SCI). Though the ultimate recovery would be repairing or regenerating new axons across the spinal lesion (potentially by stem cells or other transplants and neurotropic factors), challenges to achieve this as well as recent technological advancements demand the development of new neuroprosthetic devices to restore such motor functions following the injuries. In this chapter, the authors discuss available therapies for the rehabilitation of SCI paraplegics and some new potential interventions that still require clinical tests. They also propose brain-machine-spinal cord interface as a future neuroprosthesis following motor complete SCI.

2019 ◽  
Author(s):  
S Rezk ◽  
A Althani ◽  
A Abd-Elmaksoud ◽  
M Kassab ◽  
A Farag ◽  
...  

AbstractIn the present study we developed an excitotoxic spinal cord injury (SCI) model using kainic acid (KA) to evaluate of the therapeutic potential of human olfactory bulb neural stem cells (h-OBNSCs) for spinal cord injury (SCI). In a previous study, we assessed the therapeutic potential of these cells for SCI; all transplanted animals showed successful engraftment. These cells differentiated predominantly as astrocytes, not motor neurons, so no improvement in motor functions was detected. In the current study we used estrogen as neuroprotective therapy before transplantation of OBNSCs to preserve some of endogenous neurons and enhance the differentiation of these cells towards neurons. The present work demonstrated that the h-GFP-OBNSCs were able to survive for more than eight weeks after sub-acute transplantation into injured spinal cord. Stereological quantification of OBNSCs showed approximately a 2.38-fold increase in the initial cell population transplanted. 40.91% of OBNSCs showed differentiation along the neuronal lineages, which was the predominant fate of these cells. 36.36% of the cells differentiated into mature astrocytes; meanwhile 22.73% of the cells differentiated into oligodendrocytes. Improvement in motor functions was also detected after cell transplantation.


2018 ◽  
Vol 35 (15) ◽  
pp. 1765-1780 ◽  
Author(s):  
Jean-Claude Stamegna ◽  
Kevin Sadelli ◽  
Guy Escoffier ◽  
Stéphane D. Girard ◽  
Antoine D. Veron ◽  
...  

2021 ◽  
Vol 405 ◽  
pp. 113205
Author(s):  
Hatef Ghasemi Hamidabadi ◽  
Sara Simorgh ◽  
Seyed Kamran Kamrava ◽  
Zeinab Namjoo ◽  
Zohreh Bagher ◽  
...  

2018 ◽  
Vol 27 (6) ◽  
pp. 907-915 ◽  
Author(s):  
Zhifeng Xiao ◽  
Fengwu Tang ◽  
Yannan Zhao ◽  
Guang Han ◽  
Na Yin ◽  
...  

Stem cells and biomaterials transplantation hold a promising treatment for functional recovery in spinal cord injury (SCI) animal models. However, the functional recovery of complete SCI patients was still a huge challenge in clinic. Additionally, there is no clinical standard procedure available to diagnose precisely an acute patient as complete SCI. Here, two acute SCI patients, with injury at thoracic 11 (T11) and cervical 4 (C4) level respectively, were judged as complete injury by a stricter method combined with American Spinal Injury Association (ASIA) Impairment Scale, magnetic resonance imaging (MRI) and nerve electrophysiology. Collagen scaffolds, named NeuroRegen scaffolds, with human umbilical cord mesenchymal stem cells (MSCs) were transplanted into the injury site. During 1 year follow up, no obvious adverse symptoms related to the functional scaffolds implantation were found after treatment. The recovery of the sensory and motor functions was observed in the two patients. The sensory level expanded below the injury level, and the patients regained the sense function in bowel and bladder. The thoracic SCI patient could walk voluntary with the hip under the help of brace. The cervical SCI patient could raise his lower legs against the gravity in the wheelchair and shake his toes under control. The injury status of the two patients was improved from ASIA A complete injury to ASIA C incomplete injury. Furthermore, the improvement of sensory and motor functions was accompanied with the recovery of the interrupted neural conduction. These results showed that the supraspinal control of movements below the injury was regained by functional scaffolds implantation in the two patients who were judged as the complete injury with combined criteria, it suggested that functional scaffolds transplantation could serve as an effective treatment for acute complete SCI patients.


2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.


2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.


2021 ◽  
Vol 116 ◽  
pp. 101978
Author(s):  
Reza Asadi-Golshan ◽  
Vahid Razban ◽  
Esmaeil Mirzaei ◽  
Abdolkarim Rahmanian ◽  
Sahar Khajeh ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  

Abstract Background Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. Methods We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA. Results CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased. Conclusion The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.


Author(s):  
Akbar Hojjati Najafabadi ◽  
Saeid Amini ◽  
Farzam Farahmand

Physical problems caused by fractures, aging, stroke, and accidents can reduce foot power; these, in the long term, can dwindle the muscles of the waist, thighs, and legs. These conditions provide the basis for the invalidism of the harmed people. In this study, a saddle-walker was designed and evaluated to help people suffering from spinal cord injury and patients with lower limb weakness. This S-AD works based on body weight support against the previously report designs. This saddle-walker consisted of a non-powered four-wheel walker helping to walk and a powered mechanism for the sit-to-stand (STS) transfer. A set of experiments were done on the STS in the use of the standard walker and the saddle-assistive device(S-AD). A comparison of the results showed that this device could reduce the vertical ground reaction force (GRF) of the legs up to 70%. Using this device could help a wide range of patients with lower limb weakness and SCI patients in changing from sitting to standing.


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