scholarly journals Neuroinflammation as Part of a Possible Neuro-regeneration in a Patient with ASIA-A Scale Using Combinatorial Biologics: Bioquantine® and Allogeneic Mesenchymal Stem Cells

2019 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Sensory Loss ◽  
Spinal Shock ◽  
Cord Injury ◽  
Spastic Paresis ◽  
Complete Spinal Cord Injury ◽  
Spinal Cord Function

A complete spinal cord injury (SCI) is the complete sensory and motor loss below the site of spinal cord injury following acute or chronic destruction, compression, or ischemia of the spinal cord. Initially, this may present as spinal shock, which is an acute physiological loss or depression of spinal cord function. It presents as a flaccid are flexic paralysis below the level of the injury with autonomic features (e.g., hypotension and bradycardia). After some days to weeks the spinal shock wears off and a complete spinal cord injury may remain. It presents with spastic paresis, hyperreflexia, and continued sensory loss.

scholarly journals Clinical Study of NeuroRegen Scaffold Combined with Human Mesenchymal Stem Cells for the Repair of Chronic Complete Spinal Cord Injury

2017 ◽  
Vol 26 (5) ◽  
pp. 891-900 ◽  
Author(s):  
Yannan Zhao ◽  
Fengwu Tang ◽  
Zhifeng Xiao ◽  
Guang Han ◽  
Nuo Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Perioperative Complications ◽  
Motor Evoked Potential ◽  
Neurophysiological Monitoring ◽  
Human Umbilical Cord ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Regeneration of damaged neurons and recovery of sensation and motor function after complete spinal cord injury (SCI) are challenging. We previously developed a collagen scaffold, NeuroRegen, to promote axonal growth along collagen fibers and inhibit glial scar formation after SCI. When functionalized with multiple biomolecules, this scaffold promoted neurological regeneration and functional recovery in animals with SCI. In this study, eight patients with chronic complete SCI were enrolled to examine the safety and efficacy of implanting NeuroRegen scaffold with human umbilical cord mesenchymal stem cells (hUCB-MSCs). Using intraoperative neurophysiological monitoring, we identified and surgically resected scar tissues to eliminate the inhibitory effect of glial scarring on nerve regeneration. We then implanted NeuroRegen scaffold loaded with hUCB-MSCs into the resection sites. No adverse events (infection, fever, headache, allergic reaction, shock, perioperative complications, aggravation of neurological status, or cancer) were observed during 1 year of follow-up. Primary efficacy outcomes, including expansion of sensation level and motor-evoked potential (MEP)-responsive area, increased finger activity, enhanced trunk stability, defecation sensation, and autonomic neural function recovery, were observed in some patients. Our findings suggest that combined application of NeuroRegen scaffold and hUCB-MSCs is safe and feasible for clinical therapy in patients with chronic SCI. Our study suggests that construction of a regenerative microenvironment using a scaffold-based strategy may be a possible future approach to SCI repair.

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway

2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Inflammatory Factors ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Apoptosis And Inflammation

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.

scholarly journals CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

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.

scholarly journals Developmental Regulation of TAC1 in Peptidergic-Induced Human Mesenchymal Stem Cells: Implication for Spinal Cord Injury in Zebrafish

2012 ◽  
Vol 21 (2) ◽  
pp. 308-320 ◽  
Author(s):  
Nitixa Patel ◽  
Tilman E. Klassert ◽  
Steven J. Greco ◽  
Shyam A. Patel ◽  
Jessian L. Munoz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Developmental Regulation ◽  
Human Mesenchymal Stem Cells ◽  
Cord Injury
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