scholarly journals Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells

2021 ◽  
Vol 67 (9) ◽  
pp. 1342-1348
Author(s):  
Wu-Sheng Deng ◽  
Xiao-Yin Liu ◽  
Ke Ma ◽  
Bing Liang ◽  
Ying-Fu Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Motor Function ◽  
Human Umbilical Cord ◽  
Cord Injury ◽  
Complete Spinal Cord Injury ◽  
Recovery Of Motor Function

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.

Intracerebroventricular Delivery of Human Umbilical Cord Mesenchymal Stem Cells as a Promising Therapy for Repairing the Spinal Cord Injury Induced by Kainic Acid

2019 ◽  
Vol 16 (1) ◽  
pp. 167-180 ◽  
Author(s):  
Fabián Nishida ◽  
María F. Zappa Villar ◽  
Carolina N. Zanuzzi ◽  
María S. Sisti ◽  
Agustina E. Camiña ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Kainic Acid ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
Cord Injury

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.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells-Secreted TSG-6 Is Anti-Inflammatory and Promote Tissue Repair After Spinal Cord Injury

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110106
Author(s):  
Ziling Liao ◽  
Wei Wang ◽  
Weiyue Deng ◽  
Yuying Zhang ◽  
Aishi Song ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Tissue Repair ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Cord Injury ◽  
Tissue Recovery

Spinal cord injury (SCI) causes patients paralysis and hard to recover. The therapeutic effects of current clinical drugs are accompanied by side effects. In recent years, stem cell therapy has attracted the attention of researchers. Human umbilical cord mesenchymal stem cells (hucMSCs) have been widely used in various diseases due to their excellent paracrine function. TNF-stimulated gene 6 (TSG-6), a secretion factor of stem cells, may play an important role in hucMSCs in the treatment of SCI. So we conducted an experiment to explore its effect. We first observed that the expression of TSG-6 increased in SCI rats after injected with hucMSCs. Then, we used siRNA to knowdown the expression of TSG-6. We treated SCI rats with TSG-6-knockdown hucMSCs. Without TSG-6 expression, hucMSCs treatment made the tissue recovery worse and the number of Nissl bodies less. Meanwhile, neutrophils infiltrated more in the damaged parts. Our research also proved that TSG-6 may help demyelination recovering and alleviate astrocytes gathering in the injury sites. Our study revealed that hucMSCs secreted TSG-6 may decrease the degeneration of myelin sheath, reduce inflammation, decrease neuron loss and promote tissue repair. These results provided a new therapeutic factor for the treatment of SCI.

scholarly journals Extracellular vesicles derived from CD73 modified human umbilical cord mesenchymal stem cells ameliorate inflammation after spinal cord injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiao Zhai ◽  
Kai Chen ◽  
Huan Yang ◽  
Bo Li ◽  
Tianjunke Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Human Umbilical Cord ◽  
M1 Polarization ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI. Methods CD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications. Results CD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4. Conclusions CD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy. Graphical Abstract

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