间充质干细胞来源外泌体在骨关节炎治疗中的作用

骨关节炎(OA)是最常见的慢性退行性骨关节疾病,目前对骨关节炎的治疗还没有特效疗法。间充质干细胞(MSC)对软骨修复有较好的疗效,间充质干细胞来源外泌体可能在这一治疗过程中发挥重要作用。外泌体是细胞间的通讯载体,能在细胞间传递生物活性脂质、核酸以及蛋白质等生物活性分子对骨关节炎产生一定影响。本文就探讨间充质干细胞来源的外泌体治疗骨关节炎过程中的作用机制与可行性做出综述。     

间充质干细胞来源外泌体在膝骨关节炎微环境中的作用

骨关节炎是一种涉及所有关节成分（包括关节软骨、软骨下骨、滑膜、韧带、关节囊和关节周围肌肉）的关节退行性疾病,会导致严重的残疾,其中最常见的是膝骨关节炎（knee osteoarthritis,KOA）。外泌体是一种由不同细胞分泌的直径为40~100 nm的胞外囊泡,可以传递DNA、微小RNA、mRNA、蛋白质等多种物质,并通过多种方式进行细胞间的信息传递和功能调节。间充质干细胞（mesenchymal stem cells,MSCs）可以从骨髓、脂肪、滑膜及外周血等组织分离,是一类具有多向分化潜能的祖细胞,以干细胞为基础的疗法可以修复软骨损伤,对抗KOA的发展,间充质干细胞能够分泌多种营养因子来调节受损的微环境,其中间充质干细胞来源的外泌体被认为在KOA炎症反应及软骨细胞代谢中发挥着重要的作用,其能够调节膝骨关节微环境中B细胞、T细胞、滑膜细胞、软骨细胞代谢及其细胞外基质的分解与合成平衡,维持软骨稳态。近期有多项研究表明,不同组织来源的间充质干细胞外泌体对骨关节炎均有明确的治疗作用,本文就MSCs来源的外泌体治疗KOA的具体机制进行综述,以期对干细胞治疗KOA提供理论依据。     

外泌体源性环状RNA在肺癌病理进程及诊疗中的研究进展

外泌体是具有细胞间信号传递生物学功能的一种脂质双分子层囊泡,其内包含RNA、DNA、蛋白质等生物分子,近年来其在疾病发生发展、早期诊断和治疗等方面的作用被广泛研究。环状RNA (circular RNA, circRNA)是一类可以存在于外泌体中的单链闭合环状RNA。越来越多的研究表明外泌体源性circRNA与肺癌的发生发展密切相关,为了更好地了解外泌体源性circRNA在肺癌病理进程中的作用,本文重点讲述了外泌体源性circRNA在肺癌增殖、侵袭与转移、免疫逃逸和耐药中的作用,以及其在肺癌诊断、预后评估及治疗方面的研究进展。     

间充质干细胞来源外泌体促心肌梗死血管新生及其机制研究进展

血管新生(angiogenesis)是机体内一个复杂的生理学和病理学过程,是治疗缺血性疾病的重要措施。大量实验研究已表明间充质干细胞(mesenchymal stem cells, MSCs)等干细胞移植可促进心肌梗死后血管新生,近期研究证实这一作用可能主要通过分泌外泌体形式介导。外泌体(exosome)通过传递与血管新生相关微RNA(microRNA, mi RNA)或蛋白质等生物活性物质,调控靶器官中与血管新生相关通路的基因表达,提高内皮细胞在缺血缺氧环境下的存活、迁移、成管能力,促进心肌梗死区域血管新生。通过基因修饰手段增强外泌体介导的心脏修复作用,以及将外泌体与生物活性肽结合形成工程外泌体来靶向缺血心肌治疗,是目前外泌体在心血管领域的热点研究方向。本文结合近年外泌体研究的相关文献,就MSCs来源外泌体促进心肌梗死血管新生的具体机制及现状研究作一综述。     

间充质干细胞来源的外泌体治疗心肌梗死的研究进展

外泌体是一种小的单层膜结构的细胞外小囊泡,可在细胞间传递蛋白质、脂质、mRNA和miRNA等物质。间充质干细胞来源的外泌体可以作为无细胞系统减少心肌梗死后梗死面积、促进心肌再生并改善心功能,其作用机制可能与激活抗炎和促存活通路、调控细胞自噬和促进血管新生等有关。通过表面修饰或改造来源细胞以提高外泌体的靶向性或改变其内含物质值得深入研究。     

ATDC5来源外泌体包载小分子药物5Z-7-Oxozeaenol治疗骨关节炎

骨关节炎(osteoarthritis,OA)是一种常见的退行性关节疾病。研究表明,TAK1的抑制剂小分子药物5Z-7- Oxozeaenol(5Z-7),用于治疗OA时直接将药物进行频繁关节腔注射,药物的治疗效果有限。本研究选取小鼠胚胎瘤成软骨细胞系(ATDC5),是一种理想的成软骨细胞模型,其增殖速度和培养稳定性均优于间充质干细胞,用于提取外泌体作为药物的载体。本研究提取ATDC5来源的外泌体(ATDC5-Exos),包载药物5Z-7。在炎性细胞因子诱导大鼠软骨细胞模型中,载药外泌体可以促进合成代谢相关基因Col2a1、Sox9的表达,抑制分解代谢相关基因Adamts5、Mmp13的表达。本研究使用8周龄雄性小鼠,行前交叉韧带离断术(ACLT)诱导OA小鼠模型,关节腔注射外泌体或载药外泌体治疗,取膝关节石蜡切片进行组织学评估。结果显示,载药外泌体可缓解创伤后OA模型的病理表型。结合Micro-CT影像学结果显示,治疗能改善ACLT术后膝关节软骨下骨骨小梁的流失和骨赘减少,关节表面更为光滑。本研究证实,ATDC5-Exos包载药物5Z-7在体内和体外实验中均可缓解OA表型。外泌体包载递送5Z-7减少了药物的用量和给药频率,且药物和外泌体可以叠加治疗改善OA的效果。     

外泌体在病毒感染诊断和治疗中的作用研究

外泌体是多泡体与细胞质膜融合后释放的细胞外囊泡.它们携带有源自分泌细胞的功能性蛋白质、脂质和核酸,能够介导细胞间通信,并在生物体的致病过程中发挥重要作用.当前,对外泌体在病毒感染中的作用机制研究,以及外泌体作为病毒感染诊断和治疗的潜在标志物研究仍处于初级阶段.首先阐述了外泌体的组成和生物学发生机制;然后重点阐述了外泌体...     

间充质干细胞来源的外泌体治疗缺血性脑卒中的研究进展

外泌体是直径为30～150 nm的细胞外囊泡,内含细胞来源的核酸和蛋白质等生物活性分子,在细胞间通讯过程中发挥重要作用。间充质干细胞来源的外泌体可有效转运mRNA、microRNA及蛋白质等生物活性物质,具有促进血管生成、减轻炎症反应、调节自噬水平、抑制细胞凋亡和焦亡等重要生物学功能,其在改善神经系统疾病预后方面有着良好的临床应用前景。该文就间充质干细胞来源的外泌体对缺血性脑卒中的神经保护作用及机制进行了综述,并讨论了靶向修饰的外泌体在治疗缺血性脑卒中的应用,以期为后续研究提供参考。     

ATL-derived exosomes modulate mesenchymal stem cells: potential role in leukemia progression

Background

Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia. We hypothesized that the cargo of ATL-derived exosomes is transferred to MSCs and alter their functional behavior to support the establishment of the appropriate microenvironment for leukemia.

Results

We showed that both ATL cells (C81 and HuT-102) and patient-derived cells released Tax-containing exosomes. The cargo of HuT-102-derived exosomes consisted of miR-21, miR-155 and vascular endothelial growth factor. We demonstrated that HuT-102-derived exosomes not only deliver Tax to recipient MSCs, but also induce NF-κB activation leading to a change in cellular morphology, increase in proliferation and the induction of gene expression of migration and angiogenic markers.

Conclusions

This study demonstrates that ATL-derived exosomes deliver Tax and other leukemia-related genes to MSCs and alter their properties to presumably create a more conducive milieu for leukemia. These findings highlight the contribution of leukemia-derived exosomes in cellular transformation and their potential value as biomarkers and targets in therapeutic strategies.

     

间充质干细胞外泌体对海马星形胶质细胞活化的抑制作用研究

目的 探讨间充质干细胞外泌体(MSC-Exo)对海马星形胶质细胞活化的抑制作用.方法 实验通过超速离心法提取脐带MSC-Exo,并使用PKH-26染料标记;MSC-Exo预处理原代海马星形胶质细胞后使用脂多糖(LPS)诱导细胞活化,并分为对照组、LPS组和LPS+MSC-Exo组,进而行免疫细胞化学检测胶质纤维酸性蛋白...     

间充质干细胞源性外泌体miRNAs参与损伤心血管细胞修复的研究进展

外泌体是由各种组织和细胞所释放的细胞外囊泡,在细胞之间充当各种分子(包括蛋白质,脂质和RNA)的载体,从而调节或干预特定的生理过程.MiRNAs是一类小的非编码RNA,能够靶向多个mRNA并诱导其降解或翻译抑制以调控相关基因表达.目前对外泌体内微小RNA(miR-NAs)的研究最为广泛.间充质干细胞(MSCs)是一种多...     

The potential role of exosomes in the diagnosis and therapy of ischemic diseases

In the past, exosomes have been thought of as cellular dust. Today, they are thought to be carriers of real biomarkers and intercellular biological information. The composition of exosomes differs according to their source, and the subsequent information they carry, such as protein, microRNA or mRNA, may also be different. Recent studies have demonstrated that exosomes in ischemic diseases can help to make an early diagnosis, and in cellular experiments and animal models, exosomes promote angiogenesis, restrain cell apoptosis and reduce inflammation, among other actions, to protect ischemic organs. There is evidence that these protective effects are related to microRNAs in exosomes. In this review, we discuss the use of exosomes for early diagnosis of ischemic diseases and recent advances in the therapeutic use of exosomes in cell and mammalian models of ischemic diseases.     

K562 cell-derived exosomes suppress the adhesive function of bone marrow mesenchymal stem cells via delivery of miR-711

A failure of bone marrow mesenchymal stem cells (BM-MSCs) to adhere to hematopoietic cells is an essential cause of the progression of chronic myelogenous leukemia and is also a cause of failure of bone marrow (BM) transplantation, but the exact mechanisms of this have not been fully elucidated. Recent studies have indicated that microRNAs (miRNAs) are contained in leukemia-derived exosomes and are involved in modulating the BM microenvironment. In this study, we found that K562 cell-derived exosomes transfer miR-711 to BM-MSCs and suppress the adhesive function of BM-MSCs. Using qRT-PCR, we also confirmed a significantly higher level of miR-711 in exosomes derived from K562 cells than in exosomes derived from parental cells. The BM-MSCs co-cultured with exosomes derived from K562 cells showed a lower adhesion rate than did controls. We further demonstrated that exosomal transfer of miR-711 induced decreased adhesive abilities by inhibiting expression of adhesion molecule CD44 in BM-MSCs. In conclusion, our study reveals that K562 cell-derived exosomal miR-711 can be transferred to BM-MSCs and weaken adhesive abilities by silencing the expression of the adhesion molecule CD44.     

The role of exosomes in stroke

Molecular Biology Reports - Stroke is induced by a partial disruption of cerebral blood flow to the brain and is related to high morbidity and mortality. In the central nervous system, exosomes...     

肿瘤干细胞研究进展

在过去的十年中,肿瘤干细胞（cancer stem cell／tumor—initiating cell,CSC／TIC）虽然受到广泛重视,但也是争论的焦点。如何正确认识CSCs假说,以及CSCs的生物学特点和CSCs的治疗应用这些问题都存在巨大的争议。该文对CSCS的起源、分离鉴定的方法,以及信号通路、微环境等对cSCS的调控关系,肿瘤的最佳治疗途径等问题进行综述。     

造血干细胞研究进展

造血干细胞（hematopoietic stem cell,HSC）是成体干细胞研究领域的范式。对造血干细胞自我更新和不对称分裂分子遗传学机制的诠释,将不仅帮助理解成体干细胞“干性”维持的发育遗传学机制,也将对白血病干细胞和其他类型肿瘤干细胞的发育起源及开发针对肿瘤干细胞的靶向治疗模式产生深远的影响。