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

Abstract

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.

Identification of Cathepsin B as a Therapeutic Target for Ferroptosis of Macrophage after Spinal Cord Injury

“…The surgical procedure of spinal cord contusive injury in mice was conducted as described in our previous study [ 24 ]. Briefly, animals were anesthetized by intraperitoneally injecting them with sublethal doses of 8 mg/kg ketamine and 10 mg/kg xylazine to minimize suffering during the surgery.…”

The Role of Exosomes and Exosomal Noncoding RNAs From Different Cell Sources in Spinal Cord Injury

“…MSCs-Exos were separated and concentrated by ultracentrifugation and differential centrifugation in many studies (Huang et al, 2017 , 2020a ; Lankford et al, 2018 ; Wang et al, 2018 ; Guo et al, 2019 ; Ji et al, 2019 ; Kang et al, 2019 ; Li et al, 2019 ; Li C. et al, 2020 ; Li et al, 2021 ; Chen et al, 2021 ; Cheng et al, 2021 ; Han et al, 2021 ; Jia et al, 2021 ; Jiang and Zhang, 2021 ; Liu W. Z. et al, 2021 ; Liu et al, 2022 ; Nakazaki et al, 2021 ; Nie and Jiang, 2021 ; Noori et al, 2021 ; Sheng et al, 2021 ; Xiao et al, 2021 ; Xin et al, 2021 ; Zhang A. et al, 2021 ; Liang et al, 2022 ; Zhou et al, 2022 ) and by precipitation kits/polymer (PEG or others) in some studies (Li et al, 2018 ; Ren et al, 2019 ; Xu et al, 2019 ; Yu et al, 2019 ; Zhao et al, 2019 ; Fan et al, 2021 ; Jia et al, 2021a , b ; Kang and Guo, 2022 ). To achieve better specificity of MSCs-Exos separation, many researchers isolated MSCs-Exos using ultrafiltration-centrifugation combined with density-gradient ultracentrifugation (Liu et al, 2020 ; Shao et al, 2020 ; Chang et al, 2021 ; Luo et al, 2021 ; Huang et al, 2022 ).…”

Exosomes combined with biomaterials in the treatment of spinal cord injury

“…miR-151-3p is highly expressed in MG-Exos and plays a neuroprotective role during the repair of SCI. Meanwhile, MG-Exos can activate the p53/p21/CDK1 signaling cascade to regulate neuronal apoptosis and promote axonal growth ( Li et al, 2021b ). MG-Exos may act as an antioxidant through activation of the Keap1/Nrf2/HO-1 pathway to promote functional recovery after SCI ( Peng et al, 2021 ).…”