PDF(Pubmed)
Abstract：
UNASSIGNED: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice.
UNASSIGNED: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated.
UNASSIGNED: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization.
UNASSIGNED: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.
UNASSIGNED: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated.
UNASSIGNED: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization.
UNASSIGNED: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.
摘要：
■神经炎症是神经退行性疾病的特征。间充质干细胞来源的外泌体（MSC-exo）通过免疫调节显示出神经保护作用，但治疗效果仍不令人满意。本研究旨在通过IL-23引发来增强MSC-exo治疗小鼠视网膜变性的神经保护能力。
■在体外对MSC进行IL-23刺激，随后,分离并表征外泌体(MSC-exo和IL-23-MSC-exo)。两种视网膜变性疾病模型(NaIO3诱导的小鼠和rd10小鼠)接受这些外泌体的玻璃体内注射。通过检查视网膜结构和功能恢复来评估外泌体的功效。此外，外泌体微小RNA（miRNA）测序，并评估了外泌体对M1和M2小胶质细胞表型转变的影响。
■IL-23引发的MSC衍生的外泌体（IL-23-MSC-exo）在保护感光细胞和视网膜色素上皮（RPE）细胞免受退行性损害和促进与MSC-exo相比，NaIO3诱导的视网膜变性小鼠和rd10小鼠的视网膜神经功能恢复方面表现出增强的能力。IL-23引发的MSC中通过Drosha敲低的外泌体miRNA抑制将消除IL-23-MSC-exo的神经保护作用，突出了miRNA依赖性机制。生物信息学分析,随着进一步的体内生物学研究，显示IL-23引发在MSC-exo中诱导了一组抗炎miRNA，提示M1向M2的小胶质细胞极化转变。
■IL-23引发是增强MSC-exo治疗视网膜变性的免疫调节和神经保护作用的潜在途径。
■在体外对MSC进行IL-23刺激，随后,分离并表征外泌体(MSC-exo和IL-23-MSC-exo)。两种视网膜变性疾病模型(NaIO3诱导的小鼠和rd10小鼠)接受这些外泌体的玻璃体内注射。通过检查视网膜结构和功能恢复来评估外泌体的功效。此外，外泌体微小RNA（miRNA）测序，并评估了外泌体对M1和M2小胶质细胞表型转变的影响。
■IL-23引发的MSC衍生的外泌体（IL-23-MSC-exo）在保护感光细胞和视网膜色素上皮（RPE）细胞免受退行性损害和促进与MSC-exo相比，NaIO3诱导的视网膜变性小鼠和rd10小鼠的视网膜神经功能恢复方面表现出增强的能力。IL-23引发的MSC中通过Drosha敲低的外泌体miRNA抑制将消除IL-23-MSC-exo的神经保护作用，突出了miRNA依赖性机制。生物信息学分析,随着进一步的体内生物学研究，显示IL-23引发在MSC-exo中诱导了一组抗炎miRNA，提示M1向M2的小胶质细胞极化转变。
■IL-23引发是增强MSC-exo治疗视网膜变性的免疫调节和神经保护作用的潜在途径。
