scholarly journals Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix Promotes Structural and Functional Recovery Following Spinal Cord Injury in Rats

2018 ◽  
Vol 9 ◽  
Author(s):  
Yana O. Mukhamedshina ◽  
Elvira R. Akhmetzyanova ◽  
Alexander A. Kostennikov ◽  
Elena Y. Zakirova ◽  
Luisa R. Galieva ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Functional Recovery ◽  
Fibrin Matrix ◽  
Cord Injury

scholarly journals Safety and Feasibility of Autologous Olfactory Ensheathing Cell and Bone Marrow Mesenchymal Stem Cell Co-transplantation in Chronic Human Spinal Cord Injury: A Clinical Trial

2021 ◽  
Author(s):  
Homa Zamani ◽  
Mina Soufizomorrod ◽  
Saeed Oraee-Yazdani ◽  
Dariush Naviafar ◽  
Mohammadhosein Akhlaghpasand ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Safety Issue ◽  
Functional Evaluation ◽  
Olfactory Ensheathing Cell ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Cell-based therapies are considered as promising strategies for spinal cord regeneration. However, a combinatorial cell therapeutic approach seems more beneficial as it can target various aspects of the injury. Here, we assessed the safety and feasibility of autologous mucosal Olfactory Ensheathing Cell (OEC) and bone marrow Mesenchymal Stem Cell (MSC) co-transplantation in patients with chronic, complete (American Spinal Injury Association (ASIA) classification A) Spinal Cord Injury (SCI). Three patients with the traumatic SCI of the thoracic level were enrolled. They received autologous OEC and MSC combination through the lumbar puncture. All adverse events and possible functional outcomes were documented performing pre- and post-operative general clinical examination, Magnetic Resonance Imaging (MRI), neurological assessment based on the International Standard of Neurological Classification for SCI (ISNCSCI), and functional evaluation using Spinal Cord Independence Measure version III (SCIM III). No serious safety issue was recorded during the two years of follow-up. MRI findings remained unchanged with no neoplastic tissue formation. ASIA impairment scale improved from A to B in one of the participants. SCIM III evaluation also showed some degrees of progress in this patient's quality of life. The two other patients had negligible or no improvement in their sensory scores without any changes in the ASIA impairment scale and SCIM III scores. No motor recovery was observed in any of the participants. Overall, this two-year trial was not associated with any adverse findings, which may suggest the safety of autologous OEC and bone marrow MSC combination for the treatment of human SCI.This study was registered at the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20160110025930N2/ registration date: 2018-09-29).

Adipose mesenchymal stem cell transplantation alleviates spinal cord injury-induced neuroinflammation partly by suppressing the Jagged1/Notch pathway

2019 ◽  
Author(s):  
Zhou Zhilai ◽  
Tian Xiaobo ◽  
Mo Biling ◽  
Xu Huali ◽  
Yao Shun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Therapeutic Effects ◽  
Mesenchymal Stem Cell Transplantation ◽  
Cord Injury

Abstract Background The therapeutic effects of adipose-derived mesenchymal stem cell (ADSC) transplantation have been demonstrated in several models of central nervous system (CNS) injury and are thought to involve the modulation of the inflammatory response. However, the exact underlying molecular mechanism is poorly understood. Activation of the Jagged1/Notch signaling pathway is thought to involve inflammatory and gliotic events in the CNS. Here, we elucidated the effect of ADSC transplantation on the inflammatory reaction after spinal cord injury (SCI) and the potential mechanism mediated by Jagged1/Notch signaling pathway suppression.Methods Using a mouse model of compression SCI, ADSCs and Jagged1 small interfering RNA (siRNA) were injected into the spinal cord. Locomotor function, spinal cord tissue morphology and the levels of various proteins and transcripts were compared between groups.Results ADSC treatment resulted in significant downregulation of proinflammatory mediator expression and reduced ionized calcium binding adapter molecule 1 (Iba1) and ED1 staining in the injured spinal cord, promoting the survival of neurons. These changes were accompanied by improved functional recovery. The augmentation of the Jagged1/Notch signaling pathway after SCI was suppressed by ADSC transplantation. The inhibition of the Jagged1/Notch signaling pathway by Jagged1 siRNA resulted in a decrease in SCI-induced proinflammatory cytokines as well as the activation of microglia. Furthermore, Jagged1 knockdown suppressed the phosphorylation of JAK/STAT3 following SCI.Conclusion The results of this study demonstrated that the therapeutic effects of ADSCs in SCI mice were partly due to Jagged1/notch signaling pathway inhibition and a subsequent reduction in JAK/STAT3 phosphorylation.

scholarly journals IL-1β-induces NF-κB and upregulates microRNA-372 to inhibit spinal cord injury recovery

2017 ◽  
Vol 117 (6) ◽  
pp. 2282-2291 ◽  
Author(s):  
Wei Zhou ◽  
Tongzhou Yuan ◽  
Youshui Gao ◽  
Peipei Yin ◽  
Wei Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Functional Recovery ◽  
Neuronal Damage ◽  
Critical Role ◽  
Myeloperoxidase Activity ◽  
Cell Transplant ◽  
Tissue Water ◽  
Cord Injury

Excessive inflammation including IL-1β-initiated signaling is among the earlies reactions that can cause neuronal damage following spinal cord injury (SCI). It has been suggested that microRNAs may participate in stem cell repair to facilitate functional recovery following SCI. In this study we have shown that in cultured human neural stem cells (hNSC), IL-1β reduced the expression of both KIF3B (kinesin family member 3B) and NOSIP (nitric oxide synthase-interacting protein), two key modulators for restricting inflammation and promoting neuronal regeneration. The induction of microRNA-372 (miR-372) by IL-1β is specifically responsible for the inhibition of KIF3B and NOSIP. The 3′-untranslated regions (UTRs) of both KIF3B and NOSIP contain targeting sequences to miR-372 that directly inhibit their expression. Moreover, we found that the expression of miR-372 was stimulated in hNSC by IL-1β through an NF-κB binding site at its promoter region. Finally, stable overexpression of miR-372 inhibitor in hNSC rescued the IL-1β-induced impairment as shown by significant improvements in tissue water content, myeloperoxidase activity, and behavioral assessments in SCI rats. These findings suggest a critical role of miR-372 in inflammatory signaling and pinpoint a novel target for the treatment of acute SCI. NEW & NOTEWORTHY Our data demonstrate that IL-1β can impair the functional recovery of neural stem cell transplant therapy for spinal cord injury (SCI) treatment in rats. This effect is dependent on microRNA-372 (miR-372)-dependent gene repression of KIF3B and NOSIP. Therefore, specific knockdown of miR-372 may provide benefits for SCI treatments.

Mesenchymal stem cell therapy improves erectile dysfunction in experimental spinal cord injury

2019 ◽  
Vol 32 (3) ◽  
pp. 308-316 ◽  
Author(s):  
Ömercan Albayrak ◽  
Tarık Emre Şener ◽  
Mehmet Erşahin ◽  
Suna Özbaş-Turan ◽  
Ceyda Ekentok ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Erectile Dysfunction ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Mesenchymal Stem Cell Therapy ◽  
Experimental Spinal Cord Injury ◽  
Cord Injury
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