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

Bone Marrow Mesenchymal Stem Cell-Derived Exosome-Educated Macrophages Promote Functional Healing After Spinal Cord Injury.
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骨髓间充质干细胞衍生的外泌体培养的巨噬细胞促进脊髓损伤后的功能性愈合

DOI:
10.3389/fncel.2021.725573
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发表时间:
2021
影响因子:
5.3
通讯作者:
Hu J
Hu J
中科院分区:
医学2区
文献类型:
--
作者:
Li C;Qin T;Zhao J;He R;Wen H;Duan C;Lu H;Cao Y;Hu J

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脊髓损伤是一种严重的中枢神经系统(CNS)创伤和疾病的部位,没有有效的治疗策略。神经血管损伤在脊髓损伤(SCI)后自发发生,导致运动和感觉功能的不可逆丧失。骨髓间充质干细胞(BMSC)来源的外泌体训练的巨噬细胞(EEM)作为SCI治疗的候选治疗药物具有很大的特点。EEM是否能促进SCI后的功能性愈合尚不清楚。EEM对脊髓损伤后神经血管再生的作用有待进一步研究。我们使用从BMSC分离的外泌体产生M2样巨噬细胞,其被称为EEM,并直接使用这些EEM进行SCI治疗。我们的目的是研究EEM的影响,使用脊髓挫伤损伤小鼠模型在体内结合体外细胞功能测定,并比较结果的正常脊髓没有任何生物干预,或PBS治疗或单独的巨噬细胞(MQ)。通过神经功能测定和组织化学试验,评价EEM对血管生成和轴突再生的影响。在目前的研究中,我们发现EEM治疗有效地促进了HUVECs的血管生成活性和皮层神经元轴突生长。此外,外源性给予EEM直接进入损伤的脊髓可以通过调节血管生成和轴突生长来促进神经功能愈合。EEM治疗可以提供一种新的策略,以促进SCI和各种其他神经血管损伤疾病后的愈合。
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.
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