Intrathecal administration of the extracellular vesicles derived from human Wharton’s jelly stem cells inhibit inflammation and attenuate the activity of inflammasome complexes after spinal cord injury in rats

2020 ◽  
Author(s):  
Leila Noori ◽  
Somayeh Arabzadeh ◽  
Yousef Mohamadi ◽  
Sina Mojaverrostami ◽  
Tahmineh Mokhtari ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Extracellular Vesicles ◽  
Intrathecal Administration ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
Cord Injury

Short-term improvement in somatosensory sensitivity in patients with spinal cord injury after treatment with wharton’s jelly mesenchymal stem cells

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S71
Author(s):  
V. Sánchez-Giraldo ◽  
S. Saldarriaga-Gómez ◽  
J. España-Peña ◽  
J. Polo-Valdez ◽  
A. Ramirez ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Short Term ◽  
Wharton's Jelly ◽  
Somatosensory Sensitivity ◽  
Cord Injury

Intrathecal transplantation of Wharton’s jelly mesenchymal stem cells suppresses the NLRP1 inflammasome in the rat model of spinal cord injury

2019 ◽  
Vol 97 ◽  
pp. 1-8 ◽  
Author(s):  
Yousef Mohamadi ◽  
Seyed Mohammad Hossein Noori Moghahi ◽  
Mahboubeh Mousavi ◽  
Maryam Borhani-Haghighi ◽  
Farid Abolhassani ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
Nlrp1 Inflammasome ◽  
Cord Injury ◽  
Intrathecal Transplantation

scholarly journals The Therapeutic Potential of Conditioned Medium from Human Breast Milk Stem Cells in Treating Spinal Cord Injury

2020 ◽  
Vol 14 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Maryam Borhani-Haghighi ◽  
Shadan Navid ◽  
Yousef Mohamadi
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Breast Milk ◽  
Conditioned Medium ◽  
Rat Model ◽  
Intrathecal Administration ◽  
Human Breast Milk ◽  
Human Breast ◽  
Cord Injury

Study Design: Experimental animal study.Purpose: This study investigated the therapeutic effects of human breast milk stem cell (BMSC)-conditioned medium (BMSC-CM) in a model of spinal cord injury (SCI) in male Sprague-Dawley rats.Overview of Literature: SCI is one of the leading causes of disability in addition to sensory and motor impairment. So far, there have been no successful treatments for SCI. Given the positive outcomes associated with using stem cells and their derivatives as a treatment for various diseases, there is a growing interest in using them as an SCI treatment. Recent research has demonstrated that CM from stem cells has therapeutic advantages.Methods: Human BMSCs were isolated and characterized, and CM was subsequently collected. Animals received an intrathecal administration of BMSC-CM after SCI. The activity of caspase-3 was measured to assess apoptosis, and levels of tumor necrosis factor-α and interleukin-1β were measured to assess inflammation. Also, sensory and locomotor performances were assessed after SCI and BMSC-CM administration.Results: Administration of CM from BMSC reduced apoptosis and inflammation at the site of injury in a rat model of SCI (p<0.05). Motor, sensory, locomotor, and sensorimotor performances were significantly improved in rats that received BMSC-CM after SCI.Conclusions: Intrathecal administration of BMSC-CM improved recovery in a rat model of SCI.

scholarly journals Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis

2021 ◽  
Vol 10 (5) ◽  
pp. 328-339
Author(s):  
Xufeng Jia ◽  
Guangping Huang ◽  
Shaohua Wang ◽  
Miao Long ◽  
Xiaojun Tang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Cord Injury ◽  
Neuron Apoptosis

Aims Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. Methods In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI. Results We confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis. Conclusion Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328–339.

scholarly journals Lavandula angustifoliaExtract Improves the Result of Human Umbilical Mesenchymal Wharton’s Jelly Stem Cell Transplantation after Contusive Spinal Cord Injury in Wistar Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Kayvan Yaghoobi ◽  
Gholamreza Kaka ◽  
Korosh Mansouri ◽  
Shaghayegh Davoodi ◽  
Seyed Homayoon Sadraie ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cellular Level ◽  
Wharton’S Jelly ◽  
Female Rats ◽  
Neuroprotective Effects ◽  
Wharton's Jelly ◽  
Cord Injury ◽  
Behavior Outcomes ◽  
Primary Trauma

Introduction.The primary trauma of spinal cord injury (SCI) results in severe damage to nervous functions. At the cellular level, SCI causes astrogliosis. Human umbilical mesenchymal stem cells (HUMSCs), isolated from Wharton’s jelly of the umbilical cord, can be easily obtained. Previously, we showed that the neuroprotective effects ofLavandula angustifoliacan lead to improvement in a contusive SCI model in rats.Objective.The aim of this study was to investigate the effect ofL. angustifolia(Lav) on HUMSC transplantation after acute SCI.Materials and Methods.Sixty adult female rats were randomly divided into eight groups. Every week after SCI onset, all animals were evaluated for behavior outcomes. H&E staining was performed to examine the lesions after injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction.Results.Behavioral tests showed that the HUMSC group improved in comparison with the SCI group, but HUMSC + Lav 400 was very effective, resulting in a significant increase in locomotion activity. Sensory tests and histomorphological and immunohistochemistry analyses verified the potentiation effects of Lav extract on HUMSC treatment.Conclusion.Transplantation of HUMSCs is beneficial for SCI in rats, and Lav extract can potentiate the functional and cellular recovery with HUMSC treatment in rats after 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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