Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective,randomized, split-face study

Background

Studies have reported promising results of mesenchymal stem cell therapies for skin aging. However, in the use of mesenchymal stem cells, some drawbacks including rarely possible tumorigenicity and low engraftment rates have limited their widespread clinical use. Adipose tissue stem cell-derived exosomes (ASCEs) are emerging as effective cell-free therapeutic agents.

Aims

It was evaluated the clinical efficacy of combining the application of human ASCE-containing solution (HACS) with microneedling to treat facial skin aging.

Methods

A 12-week, prospective, randomized, split-face, comparative study was conducted. Twenty-eight individuals underwent three treatment sessions separated by 3-week intervals and were followed up for 6 weeks after the last session. At each treatment session, HACS and microneedling were administered to one side of the face, and normal saline solution and microneedling were administered to the other side as a control.

Results

The Global Aesthetic Improvement Scale score was significantly higher on the HACS-treated side than on the control side at the final follow-up visit (p = 0.005). Objective measurements obtained by different devices including PRIMOS Premium, Cutometer MPA 580, Corneometer CM 825, and Mark-Vu confirmed greater clinical improvements in skin wrinkles, elasticity, hydration, and pigmentation on the HACS-treated side than on the control side. The results of the histopathological evaluation were consistent with the clinical findings. No serious adverse events were observed.

Conclusions

These findings demonstrate that combined treatment using HACS and microneedling is effective and safe for treating facial skin aging.     

Impact of liver failure on the circulating extracellular vesicle miRNA repertoire

Background & aims

Cell-derived small extracellular vesicles (sEVs) participate in cell–cell communication via the transfer of molecular cargo including selectively enriched microRNAs (miRNAs). Utilizing advances in sEV isolation and characterization, this study investigates the impact of liver injury and dysfunction on the circulating EV-miRNA profile.

Methods

High-throughput screening of 799 sEV-miRNAs isolated from plasma was performed in patients across a spectrum of liver disorders including compensated and decompensated chronic liver disease, acute-on-chronic liver failure (ACLF), and acute liver failure, in addition to healthy controls and those with severe sepsis. miRNA levels were compared with clinical and biochemical parameters, composite scores of liver disease, and patient outcomes.

Results

miRNA screening revealed the degree of hepatic dysfunction to be the main determinant of changes in circulating sEV-miRNA profile, with liver-specific miRNA-122 being among the most highly dysregulated in severe injury. Principal components analyses of the 215 differentially expressed miRNAs showed differing profiles, particularly among those with acute liver injury and ACLF. A distinct profile of dysregulated miRNA, but not circulating cytokines, was shown to characterize ACLF, with four consensus miRNAs identified—miR-320e, miR-374-5p, miR-202-3p, and miR-1910-5p. High miR-320e was associated with poorer 90-day survival (p = 0.014) and regulated the functional gene targets IK, RPS5, MANBAL, and PEBP1.

Conclusions

This first comprehensive analysis to the best of our knowledge of patients with varying degrees and stages of liver failure demonstrates miRNA profiles specifically within the sEV compartment to be significantly altered in progressive liver disease and highlights the diagnostic and prognostic potential of sEV-miRNA in ACLF while also establishing downstream gene targets.     

miR-494-3p在胃癌患者血清外泌体中的表达及价值

摘要:目的探究微小 RNA-494-3p(miR-494-3p)在胃癌患者血清外泌体中的表达水平及临床意义。方法采用 TaqMan探针 法RT-qPCR检测44例胃癌患者和44例健康人对照组血清外泌体中miR-494-3p的表达水平,采用ROC曲线分析并评估其对 胃癌的鉴别诊断价值。同时,在14例胃癌组织和16例胃良性疾病对照患者胃组织中进行进一步验证。结果与健康人对照 组( 1.00+0.36)相比,胃癌组血清外泌体中miR-494-3p的相对表达水平(0.21+0.03)显著降低,差异有统计学意义(Z=3.64,P< 0.01);胃癌组织中miR-494-3p的相对表达水平(0.22+0.07)亦显著低于胃良性疾病对照组( 1.00+0.39),差异有统计学意义 (Z= 2.66, P<0.01)。血清外泌体miR-494-3p筛查胃癌和健康人的ROC曲线下面积( AUCROC )为0.725( 95% CI :0.622 ~0.829 , P<0.01),当ecut-off 值为0.370时,其敏感性为50.0%，特异性为86.4%,阳性预测值为63.3%,阴性预测值为78.6%,准确性为 68.2%。结论miR-494-3p 在胃癌患者血清外泌体中呈低表达，有望成为胃癌筛查和辅助鉴别诊断的潜在生物学标志物。     

Extracellular vesicles: From bone development to regenerative orthopedics

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Clinical impact of bile-derived exosomal microRNAs as novel diagnostic and prognostic biomarkers for biliary tract cancers

Sampling of bile juice during endoscopic retrograde cholangiopancreatography (ERCP) has potential benefit of being amenable to the identification of novel biomarkers in liquid biopsy. This study reports the results of a global investigation of exosomal microRNAs (miRNAs) in bile to identify potential biomarkers for biliary tract cancers (BTCs). Eighty-eight bile samples collected during ERCP (45 BTC and 43 noncancer control samples) were enrolled in this study. Eleven BTC samples and nine control samples were assigned as the discovery set. Exosomes in bile and serum samples were collected using a glass membrane column with size-controlled macroporous glass (MPG), and exosomal miRNA expression profiles were evaluated using comprehensive miRNA microarray analysis (3D-Gene). For validation, exosomal miRNA in the bile samples of 34 BTCs and 34 controls were comprehensively evaluated using 3D-Gene. In the discovery set, eight exosomal miRNAs in bile were identified as significant aberrant expression markers, while no miRNA with aberrant expression in serum was identified. In a comparison of the discovery and validation sets, miR-451a and miR-3619-3p were identified as reproducible upregulated markers, and the combination of the two bile miRNAs showed an excellent area under the curve (0.819) value for diagnosing BTCs. In addition, high miR-3619-3p expression in bile reflects poorer prognosis of BTCs (hazard ratio = 2.89). The MPG-extracted exosomal miRNAs in bile aspirated during ERCP provide a convenient new approach for diagnosing biliary diseases. Bile-derived miRNA analysis with miR-451a and miR-3619-3p represents a potentially valuable diagnostic strategy for identifying BTCs as well as a predictive indicator of BTC prognosis.     

外泌体携载微小RNA治疗骨关节炎的研究

骨关节炎(osteoarthritis，OA)因其致残率高、社会危害严重，已成为困扰全球的卫生健康问题之一。既往的常规治疗常因效果不理想，引发临床及科研层面寻求新的治疗方式。外泌体（exosome）因来源广、稳定性高等特点，逐渐成为骨科退行性疾病等的潜在应用靶点。研究发现，骨髓间充质干细胞、软骨细胞、滑膜细胞、胚胎间充质干细胞等多种细胞来源的外泌体通过携载微小RNA(microRNA , miRNA)，靶向作用于某些信号通路，进而在治疗骨关节炎等疾病中发挥重要作用。此外，制备富含特定成分的工程化外泌体，还可以提高外泌体作用的靶向性及作用浓度等。本文综述了近几年外泌体及miRNA在骨关节炎诊疗中的研究及应用，为骨关节炎诊疗方面的新策略提供参考，进而推动骨关节炎的诊疗进程。     

外泌体基于铁死亡治疗疾病的研究进展

铁死亡是一种铁依赖性非细胞凋亡的程序性细胞死亡方式。迄今为止，铁死亡已被证明参与了许多疾病的病理生理机制，如神经退行性疾病、缺血再灌注损伤、肾脏退化和癌症。外泌体作为细胞间信息传递途径，已被报道能够调节铁死亡。此外，外泌体作为一种免疫原性低、生物相容性好、效率高的药物传递载体在疾病中的应用愈发广泛。现总结外泌体基于铁死亡治疗疾病的相关案例，为进一步的研究和治疗提供新思路。