PDF(Pubmed)
Abstract：
UNASSIGNED: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin-encoding gene that leads to muscle necrosis and degeneration with chronic inflammation during growth, resulting in progressive generalized weakness of the skeletal and cardiac muscles. We previously demonstrated the therapeutic effects of systemic administration of dental pulp mesenchymal stromal cells (DPSCs) in a DMD animal model. We showed preservation of long-term muscle function and slowing of disease progression. However, little is known regarding the effects of cell therapy on the metabolic abnormalities in DMD. Therefore, here, we aimed to investigate the mechanisms underlying the immunosuppressive effects of DPSCs and their influence on DMD metabolism.
UNASSIGNED: A comprehensive metabolomics-based approach was employed, and an ingenuity pathway analysis was performed to identify dystrophy-specific metabolomic impairments in the mdx mice to assess the therapeutic response to our established systemic DPSC-mediated cell therapy approach.
UNASSIGNED: We identified DMD-specific impairments in metabolites and their responses to systemic DPSC treatment. Our results demonstrate the feasibility of the metabolomics-based approach and provide insights into the therapeutic effects of DPSCs in DMD. Our findings could help to identify molecular marker targets for therapeutic intervention and predict long-term therapeutic efficacy.
UNASSIGNED: A comprehensive metabolomics-based approach was employed, and an ingenuity pathway analysis was performed to identify dystrophy-specific metabolomic impairments in the mdx mice to assess the therapeutic response to our established systemic DPSC-mediated cell therapy approach.
UNASSIGNED: We identified DMD-specific impairments in metabolites and their responses to systemic DPSC treatment. Our results demonstrate the feasibility of the metabolomics-based approach and provide insights into the therapeutic effects of DPSCs in DMD. Our findings could help to identify molecular marker targets for therapeutic intervention and predict long-term therapeutic efficacy.
摘要：
■杜兴氏肌营养不良症（DMD）是一种遗传性疾病，由编码肌营养不良蛋白的基因突变引起，在生长过程中导致肌肉坏死和变性并伴有慢性炎症，导致骨骼肌和心肌进行性全身无力。我们先前证明了在DMD动物模型中全身施用牙髓间充质基质细胞(DPSC)的治疗效果。我们显示了长期肌肉功能的保留和疾病进展的减缓。然而,关于细胞治疗对DMD代谢异常的影响知之甚少。因此,在这里，我们旨在研究DPSC免疫抑制作用的潜在机制及其对DMD代谢的影响。
■采用了基于代谢组学的综合方法，进行了通路分析,以确定mdx小鼠中的营养不良特异性代谢组学损伤,以评估我们建立的全身性DPSC介导的细胞治疗方法的治疗反应。
■我们确定了代谢物中的DMD特异性损伤及其对全身性DPSC治疗的反应。我们的结果证明了基于代谢组学的方法的可行性，并提供了DPSC在DMD中的治疗效果的见解。我们的发现有助于确定治疗干预的分子标记靶标并预测长期治疗效果。
■采用了基于代谢组学的综合方法，进行了通路分析,以确定mdx小鼠中的营养不良特异性代谢组学损伤,以评估我们建立的全身性DPSC介导的细胞治疗方法的治疗反应。
■我们确定了代谢物中的DMD特异性损伤及其对全身性DPSC治疗的反应。我们的结果证明了基于代谢组学的方法的可行性，并提供了DPSC在DMD中的治疗效果的见解。我们的发现有助于确定治疗干预的分子标记靶标并预测长期治疗效果。
