scholarly journals Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuyo Maeda ◽  
Takashi Otsuka ◽  
Masaaki Takeda ◽  
Takahito Okazaki ◽  
Kiyoharu Shimizu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Cranial Bone ◽  
Transcranial Electrical Stimulation ◽  
Spinal Cord Tissue ◽  
Cell Based Therapy ◽  
Cord Injury

AbstractCell-based therapy using mesenchymal stem cells (MSCs) is a novel treatment strategy for spinal cord injury (SCI). MSCs can be isolated from various tissues, and their characteristics vary based on the source. However, reports demonstrating the effect of transplanted rat cranial bone-derived MSCs (rcMSCs) on rat SCI models are lacking. In this study, we determined the effect of transplanting rcMSCs in rat SCI models. MSCs were established from collected bone marrow and cranial bones. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 24 h post SCI. The recovery of motor function and hindlimb electrophysiology was evaluated 4 weeks post transplantation. Electrophysiological recovery was evaluated by recording the transcranial electrical stimulation motor-evoked potentials. Tissue repair after SCI was assessed by calculating the cavity ratio. The expression of genes involved in the inflammatory response and cell death in the spinal cord tissue was assessed by real-time polymerase chain reaction. The transplantation of rcMSCs improved motor function and electrophysiology recovery, and reduced cavity ratio. The expression of proinflammatory cytokines was suppressed in the spinal cord tissues of the rats that received rcMSCs. These results demonstrate the efficacy of rcMSCs as cell-based therapy for 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.

scholarly journals The Effect of Autologous Adipose Tissue–Derived Mesenchymal Stem Cells’ Therapy in the Treatment of Chronic Posttraumatic Spinal Cord Injury in a Domestic Ferret Patient

2020 ◽  
Vol 29 ◽  
pp. 096368972092898
Author(s):  
Agata Przekora ◽  
Lukasz Juszkiewicz
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Clinical Intervention ◽  
Experimental Treatment ◽  
Cell Based Therapy ◽  
Cord Injury ◽  
Stem Cells Therapy

Spinal cord injury (SCI) is considered as one of the most problematic neurological conditions requiring specialized clinical intervention. Taking into account that SCI is characterized by extensive loss of nerve cells, stem cell–based therapy seems to be a reasonable modern strategy to the treatment of SCI. The presented case report describes for the first time experimental treatment with the use of autologous adipose tissue–derived mesenchymal stem cells (ADSCs) of the chronic posttraumatic SCI in a domestic ferret patient with paresis of back legs. It should be noted that most reports in the available literature concern ADSC-based therapies for acute or subacute SCI treatment in other species. Application of ADSC-based therapy did not cause any adverse reactions and resulted in significant improvement of neurological and motor functions. Based on these outcomes, it may be concluded that this form of therapy is promising and may be potentially translated into clinical veterinary practice.

scholarly journals Curcumin improves human umbilical cord derived mesenchymal stem cells survival and promotes motor outcome via ERK Signaling after spinal cord injury

2020 ◽  
Author(s):  
Wu Wanjiang ◽  
Chen Xin ◽  
Chen Yaxing ◽  
Wang Jie ◽  
Zhang Hongyan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Replacement Therapy ◽  
Umbilical Cord ◽  
Motor Function ◽  
Human Umbilical Cord ◽  
Tnf Α ◽  
Cord Injury

Abstract Background Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation are assumed as a promising strategy in spinal cord injury (SCI). However, the complex pathological microenvironment after SCI induces the apoptosis of hUC-MSCs, which limits the clinical application for the cell replacement therapy. Methods In this study, in order to investigate whether combined with curcumin could strengthen the therapeutic effects of hUC-MSCs transplantation for SCI, we mediated the apoptosis of hUC-MSCs with TNF-α and transplanted hUC-MSCs into SCI rats, followed by assessed the anti- apoptosis effect and mechanism of curcumin. Results LDH release test and flow cytometry demonstrated that TNF-α led to the hUC-MSCs apoptosis and curcumin increased survival rate of hUC-MSCs with dose-dependent. In addition, we showed that the phosphorylation levels of ERK, JNK and P38 were up-regulated in the hUC-MSCs apoptosis, while curcumin strengthened the phosphorylation of ERK, but not activated the JNK and P38, which was reversed by p42/44 antagonist U0126. Furthermore, we exhibited that the motor function scores and surviving HNA-positive cells were significantly increased after curcumin combined with hUC-MSCs transplantation therapy 8 weeks post SCI, while U0126 markedly attenuated these phenomenons. Conclusions The aforementioned data confirmed that curcumin suppressed the apoptosis of hUC-MSCs through ERK signal pathway and combined curcumin with hUC-MSCs treatment improved motor function after SCI in rats. The current research provides a strong basis for hUC-MSCs replacement therapy in conjunction with curcumin in the treatment and management of SCI in human.

scholarly journals Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiao Xiao ◽  
Weiwei Li ◽  
Dingchao Rong ◽  
Zhenchao Xu ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Motor Function ◽  
Extracellular Vesicles ◽  
Human Umbilical Cord ◽  
Permanent Disability ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is a salient traumatic disease that often leads to permanent disability, and motor and sensory impairments. Human umbilical cord mesenchymal stem cells (HucMSCs) have a wide application prospect in the treatment of SCI. This study explored the repair effect of HucMSCs-derived extracellular vesicles (HucMSCs-EVs) on SCI. HucMSCs and HucMSCs-EVs were cultured and identified. The rat model of SCI was established, and SCI rats were treated with HucMSCs-EVs. The motor function of SCI rats and morphology of spinal cord tissues were evaluated. Levels of NeuN, GFAP, and NF200 in spinal cord tissues were detected and cell apoptosis was measured. SCI rats were treated with EVs extracted from miR-29b-3p inhibitor-transfected HucMSCs. The downstream gene and pathway of miR-29b-3p were examined. HucMSCs-EVs-treated rats showed obvious motor function recovery and reduced necrosis, nuclear pyknosis, and cavity. HucMSCs-EVs alleviated spinal cord neuronal injury. miR-29b-3p was poorly expressed in SCI tissues, but highly expressed in EVs and SCI rats treated with EVs. miR-29b-3p targeted PTEN. Inhibition of miR-29b-3p or overexpression of PTEN reversed the repair effect of EVs on SCI. EVs activated the AKT/mTOR pathway via the miR-29b-3p/PTEN. In conclusion, HucMSCs-EVs reduced pathological changes, improved motor function, and promoted nerve function repair in SCI rats via the miR-29b-3p/PTEN/Akt/mTOR axis.

scholarly journals Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

2018 ◽  
Vol 8 (1) ◽  
pp. 23 ◽  
Author(s):  
May-Jywan Tsai ◽  
Dann-Ying Liou ◽  
Yan-Ru Lin ◽  
Ching-Feng Weng ◽  
Ming-Chao Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Cell Based Therapy ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Related Proteins

Spinal cord injury (SCI) is a devastating neurological condition and might even result in death. However, current treatments are not sufficient to repair such damage. Bone marrow mesenchymal stem cells (BM-MSC) are ideal transplantable cells which have been shown to modulate the injury cascade of SCI mostly through paracrine effects. The present study investigates whether systemic administration of conditioned medium from MSCs (MSCcm) has the potential to be efficacious as an alternative to cell-based therapy for SCI. In neuron-glial cultures, MSC coculture effectively promoted neuronal connection and reduced oxygen glucose deprivation-induced cell damage. The protection was elicited even if neuron-glial culture was used to expose MSCcm, suggesting the effects possibly from released fractions of MSC. In vivo, intravenous administration of MSCcm to SCI rats significantly improved behavioral recovery from spinal cord injury, and there were increased densities of axons in the lesion site of MSCcm-treated rats compared to SCI rats. At early days postinjury, MSCcm treatment upregulated the protein levels of Olig 2 and HSP70 and also increased autophage-related proteins in the injured spinal cords. Together, these findings suggest that MSCcm treatment promotes spinal cord repair and functional recovery, possibly via activation of autophagy and enhancement of survival-related proteins.

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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