Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, 250012, Shandong, China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China.
Mol Med. 2024 Oct 26;30(1):186. doi: 10.1186/s10020-024-00945-1.
Apical papilla stem cells (SCAPs) exhibit significant potential for tissue repair, characterized by their anti-inflammatory and pro-angiogenic properties. Exosomes derived from stem cells have emerged as safer alternatives that retain comparable physiological functions. This study explores the therapeutic potential of exosomes sourced from SCAPs in the treatment of non-alcoholic steatohepatitis (NASH).
A NASH mouse model was established through the administration of a high-fat diet (HFD), and SCAPs were subsequently isolated for experimental purposes. A cell model of NASH was established in vitro by treating hepatocellular carcinoma cells with oleic acid (OA) and palmitic acid (PA). Exosomes were isolated via differential centrifugation. The mice were treated with exosomes injected into the tail vein, and the hepatocytes were incubated with exosomes in vitro. After the experiment, physiological and biochemical markers were analyzed to assess the effects of exosomes derived from SCAPs on the progression of NASH in both NASH mouse models and NASH cell models.
After exosomes treatment, the weight gain and liver damage induced by HFD were significantly reduced. Additionally, hepatic fat accumulation was markedly alleviated. Mechanistically, exosomes treatment promoted the expression of genes involved in hepatic fatty acid oxidation and transport, while simultaneously suppressing genes associated with fatty acid synthesis. Furthermore, the levels of serum inflammatory cytokines and the mRNA expression of inflammatory markers in liver tissue were significantly decreased. In vitro cell experiments produced similar results.
根尖乳头干细胞（SCAPs）具有显著的组织修复潜力，其抗炎和促血管生成特性是其特征之一。干细胞衍生的外泌体作为更安全的替代品出现，保留了相当的生理功能。本研究探讨了来源于 SCAP 的外泌体在治疗非酒精性脂肪性肝炎（NASH）中的治疗潜力。
通过给予高脂肪饮食（HFD）建立 NASH 小鼠模型，随后分离 SCAP 进行实验。通过用油酸（OA）和棕榈酸（PA）处理肝癌细胞在体外建立 NASH 细胞模型。通过差速离心分离外泌体。通过尾静脉注射将外泌体注入小鼠体内进行治疗，将外泌体孵育于体外培养的肝细胞中。实验结束后，分析生理生化标志物，以评估来源于 SCAP 的外泌体对 NASH 小鼠模型和 NASH 细胞模型中 NASH 进展的影响。
外泌体处理后，HFD 诱导的体重增加和肝损伤明显减轻。此外，肝脂肪堆积明显缓解。机制上，外泌体处理促进了与肝脂肪酸氧化和转运相关基因的表达，同时抑制了与脂肪酸合成相关的基因。此外，血清炎症细胞因子水平和肝组织中炎症标志物的 mRNA 表达显著降低。体外细胞实验产生了类似的结果。
