scholarly journals Bone Marrow Mesenchymal Stem Cell-Derived Exosome-Educated Macrophages Promote Functional Healing After Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Chengjun Li ◽  
Tian Qin ◽  
Jinyun Zhao ◽  
Rundong He ◽  
Haicheng Wen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cortical Neurons ◽  
Axon Growth ◽  
Sensory Function ◽  
Functional Assay ◽  
Cord Injury

The spinal cord injury is a site of severe central nervous system (CNS) trauma and disease without an effective treatment strategy. Neurovascular injuries occur spontaneously following spinal cord injury (SCI), leading to irreversible loss of motor and sensory function. Bone marrow mesenchymal stem cell (BMSC)–derived exosome-educated macrophages (EEM) have great characteristics as therapeutic candidates for SCI treatment. It remains unknown whether EEM could promote functional healing after SCI. The effect of EEM on neurovascular regeneration after SCI needs to be further explored. We generated M2-like macrophages using exosomes isolated from BMSCs, which were known as EEM, and directly used these EEM for SCI treatment. We aimed to investigate the effects of EEM using a spinal cord contusive injury mouse model in vivo combined with an in vitro cell functional assay and compared the results to those of a normal spinal cord without any biological intervention, or PBS treatment or macrophage alone (MQ). Neurological function measurements and histochemical tests were performed to evaluate the effect of EEM on angiogenesis and axon regrowth. In the current study, we found that treatment with EEM effectively promoted the angiogenic activity of HUVECs and axonal growth in cortical neurons. Furthermore, exogenous administration of EEM directly into the injured spinal cord could promote neurological functional healing by modulating angiogenesis and axon growth. EEM treatment could provide a novel strategy to promote healing after SCI and various other neurovascular injury disorders.

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).

scholarly journals The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 230
Author(s):  
Louis D. V. Johnson ◽  
Mark R. Pickard ◽  
William E. B. Johnson
Keyword(s):  
Systematic Review ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Animal Models ◽  
Mesenchymal Stem Cell ◽  
Meta Analysis ◽  
Sensory Function ◽  
Cochrane Library ◽  
Cord Injury

Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.

scholarly journals Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate Blood-Spinal Cord Barrier Disruption via the TIMP2/MMP Pathway after Acute Spinal Cord Injury

2021 ◽  
Author(s):  
Wang Xin ◽  
Shi Qiang ◽  
Ding Jianing ◽  
Liang Jiaming ◽  
Lin Fangqi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Bone ◽  
Neurological Dysfunction ◽  
Human Bone Marrow ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier

Abstract After spinal cord injury (SCI), destruction of the blood spinal cord barrier (BSCB) results in infiltration of blood cells, such as neutrophils and macrophages, leading to permanent neurological dysfunction. Previous studies have shown that human bone marrow mesenchymal stem cell (BMSC)-derived exosomes have a beneficial neuroprotective effect in SCI models. However, whether BMSC-Exos contribute to the integrity of the BSCB has not been clarified. The purpose of this study was to investigate the mechanism of BMSC-Exo-induced changes in the permeability of the BSCB after SCI. Here, we showed that BMSC-Exos can inhibit BSCB permeability damage and improve spontaneous repair in a SCI model. Importantly, tissue inhibitors of matrix metalloproteinases 2 (TIMP2) were shown to play an important role in the functions of BMSCS-Exos by inhibiting the matrix metalloproteinase (MMP) pathway, thereby mitigating the reduction in cell junction proteins. Moreover, the ability of BMSC-Exos was significantly attenuated when TIMP2 was inhibited by siRNA. This proof-of-principle study demonstrates that BMSC-Exos can preserve the integrity of the BSCB and improve functional recovery after SCI through the TIMP2/MMP signaling pathway.

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