scholarly journals STAT3 Regulates the Pathogenesis and Bone Mesenchymal Stem Cells Transplantation of Spina Bifida Aperta Through Caspase-8

2020 ◽  
Author(s):  
mingyu Jiang ◽  
Ji-cheng Dai ◽  
Ming-ying Yin ◽  
Ming-yong Ren ◽  
Nan Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Retinoic Acid ◽  
Spina Bifida ◽  
Survival Rates ◽  
Cell Number ◽  
Caspase 8 ◽  
Rat Fetuses ◽  
Spina Bifida Aperta

Abstract Objective: To investigate the influence of signal transducer and activator of transcription-3 (STAT3) on spinal cord tissue grafts of rat fetuses with spina bifida aperta. In particular, we wished to determine if STAT3 would be related to the pathogenesis of spina bifida aperta (SBA) and permit increased survival of spinal cord transplants to improve therapeutic efficiency of cellular transplantation from 20-day pregnant (E20) rats. Method: Spina bifida aperta were induced with a single intragastric retinoic acid (140 mg/kg body weight) administration on E10. STAT3 and caspase-8 expression, caspase-8 positive cells by immunofluorescence on 14, 15, 16 and 17 day in spinal cord of rat fetuses with control group and spina bifida aperta group are analysed. The pregnant rats received fetal surgery and microinjection of Mesenchymal Stem Cells (MSCs) after STAT3 transfection on 16-day pregnant (E16), 17-day pregnant (E17) and 18-day pregnant (E18), P0, P1-6 and to P7-12 of cell passages as well as different injected cell number, then sacrificed on 20-day pregnant (E20) for spine sample collection. The Number of each group was not less than seven. The spinal cord samples were collected directly to detect survival rates of MSCs and caspase-8 expression. Results: The developmental change in caspase-8 expression of spina bifida aperta was notably increased to the top on E15 compared with no SBA fetuses with Retinoic Acid. STAT3 expression in SBA rat fetuses gradually decreased with embryonic development between E14 and E15, E15 dropped down to bottom. Specifically, the number of caspase-8 positive cells on E15 in spinal cord with SBA rat fetuses was the most; and from E16, the positive cells began to decrease. Compared with STAT3 non-transfection group, MSCs combined with STAT3 transfection on E18, P7-12 and medium injection cell number can statistically improve the success rate of transplantation. In addition, caspase-8 mRNA and protein levels were significantly decreased in STAT3 transfection transplantation contrast for SBA of cellular culture medium and STAT3 non-transfection transplantation. Conclusions: STAT3 may be associated with the pathogenesis of spina bifida aperta. Furthermore, MSCs transplantation after STAT3 transfection can increase survival rates and reduce apoptosis in the spinal column through caspase-8.

scholarly journals Nanoparticles guided precise transplantation of varying numbers of mesenchymal stem cells into post–traumatic syrinx in spinal cord injury rat

2018 ◽  
pp. 49-56
Author(s):  
Chao Zhang ◽  
A.Y. Morozova ◽  
V.P. Baklaushev ◽  
I.L. Gubsky ◽  
P.A. Melnikov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Magnetic Nanoparticles ◽  
Diffusion Tensor ◽  
Cell Number ◽  
Functional Improvement ◽  
Cord Injury ◽  
Post Traumatic

Spinal cord injury (SCI) is a traumatic injury to the spinal cord which is not a consequence of the disease. Mesenchymal stem cells (MSCs) have gradually become one of the most used stem cells in research and clinic trial. Based on the previous reports employed the cells ranged from 4 • 105 to 1 • 106, the present study was performed to figure out the best number of MSCs for transplantation of the chronic SCI. Magnetic nanoparticles were used for proving the precise transplantation strategy. Using magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), diffusion tensor tractography (DTT), and behavior testing evaluations, we focused the effect of varying numbers of MSCs on reducing lesion cavity and post–traumatic syrinx formation, suppressing glial scar formation, enhancing neuronal fibers remodeling, promoting axonal regeneration and sprouting, improving vascularization, ameliorating the neuronal factors expressional level, and function improvement. Magnetic nanoparticles were precisely transplanted into the post–traumatic syrinx (PTS). MSCs can restore function after chronic SCI through stimulating the regeneration and sprouting of the axons, reducing the formation of PTS. The effect of MSCs on PTS management and functional improvement post chronic SCI was cell number–dependent, and within the range of 4 • 105 to 1 • 106, 1 • 106 cells were proved to be the best dose.

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.

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