Concise Review: Reactive Astrocytes and Stem Cells in Spinal Cord Injury: Good Guys or Bad Guys?

Stem Cells ◽  
2015 ◽  
Vol 33 (4) ◽  
pp. 1036-1041 ◽  
Author(s):  
Dunja Lukovic ◽  
Miodrag Stojkovic ◽  
Victoria Moreno-Manzano ◽  
Pavla Jendelova ◽  
Eva Sykova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Reactive Astrocytes ◽  
Concise Review ◽  
Cord Injury

scholarly journals UCHL1 inhibited by A1 astrocytes facilitates aggregates clearance to promote neural stem cells activation after spinal cord injury

2021 ◽  
Author(s):  
Lu Ding ◽  
Weiwei Chu ◽  
Yu Xia ◽  
Tian Li ◽  
Ming Shi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Protein Aggregates ◽  
Reactive Astrocytes ◽  
List Type ◽  
Cord Injury ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

AbstractSpinal cord injury (SCI) is a devastating central nervous system (CNS) disease with no satisfying therapies available. Mobilizing endogenous neural stem cells (NSCs) to trigger intrinsic regeneration exhibits promising potentials for SCI repair. However, neurogenesis from endogenous NSCs is extremely restricted in the non-neurogenic spinal cord after SCI. Accumulation of protein aggregates has been shown to impede quiescent NSCs activation and the subsequent neurogenesis. Here, we found that ubiquitin c-terminal hydrolase l-1 (UCHL1), a deubiquitinating enzyme, functioned to regulate NSCs activation and neurogenesis by reducing protein aggregations through ubiquitin-proteasome pathway (UPP) in vitro. Upregulation of UCHL1 in spinal cord NSCs of rats with complete transection SCI efficiently enhanced NSCs proliferation and neurogenesis, leading to significantly improved functional outcomes. Based on protein microarray analysis of cerebrospinal fluid (CSF), our results revealed that A1 reactive astrocytes acted to restrict NSCs neurogenesis by negatively regulating UCHL1-depentdent protein aggregates removal via the C3/Nrf2 signaling. Indeed, blockade of A1 astrocytes using neutralizing antibodies after SCI also led to NSCs activation, increased neurogenesis and remarkably enhanced motor function recovery. This study not only revealed a novel mechanism regulating NSCs-medicated neurogenesis in the spinal cord, but also provided new molecular targets for neural repair strategies after SCI.Graphical AbstractHighlightsUCHL1 facilitates NSCs activation by clearing intracellular protein aggregates through ubiquitin-proteasome approachA1 reactive astrocytes result in down-regulation of UCHL1 to inhibit spinal NSCs activation by C3 after SCIOverexpression of UCHL1 or blockade of A1 astrocytes lead to NSCs activation and neurons formation to promote SCI repair via UCHL1-proteasome pathway

scholarly journals Concise Review: Human Pluripotent Stem Cells in the Treatment of Spinal Cord Injury

Stem Cells ◽  
2012 ◽  
Vol 30 (9) ◽  
pp. 1787-1792 ◽  
Author(s):  
Dunja Lukovic ◽  
Victoria Moreno Manzano ◽  
Miodrag Stojkovic ◽  
Shom Shanker Bhattacharya ◽  
Slaven Erceg
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Concise Review ◽  
Cord Injury

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

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.

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.

Efficacy of dental pulp-derived stem cells conditioned medium loaded in collagen hydrogel in spinal cord injury in rats: Stereological evidence

2021 ◽  
Vol 116 ◽  
pp. 101978
Author(s):  
Reza Asadi-Golshan ◽  
Vahid Razban ◽  
Esmaeil Mirzaei ◽  
Abdolkarim Rahmanian ◽  
Sahar Khajeh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Conditioned Medium ◽  
Dental Pulp ◽  
Collagen Hydrogel ◽  
Cord Injury

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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