间充质干细胞对Th17/Treg平衡的影响及与IBD的关系

辅助性T细胞17（Th17）/调节性T细胞（Treg）失衡是炎症性肠病（IBD）发病的重要因素,纠正Th17/Treg细胞失衡可以减缓或抑制IBD的发生发展,成为治疗IBD的靶点。间充质干细胞具有抗炎及免疫调节功能,通过可溶性因子、细胞接触及外泌体的方式调节适应性和先天性免疫,纠正Th17/Treg失衡缓解IBD,这给IBD的治疗提供新的方向。目前,MSCs和IBD的关系研究较少,本文综述了MSCs调节Th17/Treg平衡及与IBD的关系。     

间充质干细胞来源的外泌体在炎症性肠病治疗中的作用机制及应用前景

炎症性肠病(IBD)是一种原因不明的非特异性肠道疾病,其发病率逐年提高,目前治疗药物疗效有限。间充质干细胞(MSCs)具有免疫调节、抗炎等功能,有望成为IBD的新兴治疗手段。然而MSCs因归巢能力有限,目前认为其可能通过旁分泌发挥治疗作用。MSCs分泌的外泌体(MSCs-Exo)具有MSCs的大部分功能,无恶性分化且在体内稳定存在,在干细胞治疗领域具有重要研究价值,但其在IBD中的作用机制尚不明确。本文将就MSCs-Exo对IBD的作用机制以及在IBD中的应用前景进行综述。     

间充质干细胞治疗新型冠状病毒肺炎的研究进展与应用前景

当前新型冠状病毒肺炎疾病已在全球大规模蔓延,严重危害人类的健康。新病毒感染性强并且感染后重症患者病死率较高,目前尚无有效的特异性治疗药物,因此亟待寻找安全有效的治疗方法。间充质干细胞(Mesenchymal stem cells,MSCs)具有强大的免疫调节和组织损伤修复与再生的生物学功能,因此作为一种干细胞疗法有潜力降低新冠肺炎重症患者的组织损伤和死亡率。目前,我国和国外多家研究机构已启动多项MSCs治疗新型冠状病毒肺炎的相关临床研究项目,已初步证实该疗法的安全性和有效性,因此具有非常良好的临床治疗前景。     

过表达白细胞介素10的间充质干细胞对炎症性肠病的治疗作用

炎症性肠病(inflammatory bowel disease,IBD)是一种以T细胞浸润至结肠为特征的难治性炎性自身免疫疾病。间充质干细胞 (mesenchymal stem cells,MSCs) 具有免疫抑制能力,在IBD的治疗中具有一定的潜力。但是由于MSCs在体内的免疫调节能力不稳定,所以其治疗效果会受到影响。本研究构建了过表达白细胞介素10(interleukin 10,IL-10)的工程化MSCs,并对其在IBD小鼠模型中的治疗潜力进行评估。MSCs经编码IL-10的慢病毒(lentivirus,LV)转染后,其表型和细胞增殖率均不发生变化。免疫细胞和 MSCs体外共培养的结果表明,与未修饰的MSCs相比,同过表达IL-10的MSCs共培养的免疫细胞中辅助T细胞1(T helper 1 cells,Th1)和辅助T细胞17(T helper 17 cells,Th17)数量显著性降低(P<0.05),同过表达IL-10的MSCs共培养的巨噬细胞细胞培养上清液,TNF-α含量显著性降低(P<0.0001)。右旋糖酐硫酸钠(dextran sodium sulfate,DSS)诱导IBD小鼠模型中,尾静脉注射过表达IL-10的MSCs与注射未修饰MSCs相比,过表达IL-10的MSCs具有更好的治疗效果,结肠长度、疾病活动指数(disease activity index,DAI)和结肠炎性细胞因子表达共同证明这一差异。实验结果均具有统计学差异(P<0.05)。总体而言,经LV转染过表达IL-10的MSCs可能是IBD的一种有希望的替代治疗选择。     

间充质干细胞治疗糖尿病皮肤损伤的研究进展

糖尿病患者的皮肤组织易受内源性及外源性的各种损伤,且创面具有愈合慢、易感染等特点,这种特点在下肢皮肤创伤中表现尤为突出,常伴有高截肢风险,故糖尿病皮肤损伤可严重影响患者的生活质量。间充质干细胞（MSCs）是一类多能干细胞,其具有易分离、易培养、多向分化和免疫源性低等特征,目前已被广泛应用于创伤修复、组织再生等研究。对于糖尿病皮肤损伤,MSCs的临床移植治疗已成为继药物、手术之后的又一种治疗新技术。本文结合MSCs的生物学特性,对其应用在糖尿病皮肤损伤方面的研究进展做一综述。     

模拟干细胞生长微环境以促进间充质干细胞的扩增

间充质干细胞（mesenchyrmalstemcells,MSCs）是当前在多种组织再生和细胞治疗研究中被最广泛采用的一类干细胞。但如何诱导MSCs的体外高效扩增并维持其干性特征（stemness）,从而为临床应用提供充足、优质的细胞源,是当前基础研究和临床治疗中遇到的瓶颈问题。日益增多的研究表明,机体内干细胞的自我更新与分化受其所处体内微环境的紧密调控。因此,精确模拟干细胞在体内生长的微环境已成为提高干细胞体外扩增效率的重要策略。该文就近期研究中如何模拟干细胞生长微环境诱导MSCs体外扩增并维持干细胞特性的研究做一综述,为今后MSCs的高效扩增和推进临床运用与转化提供思路。     

间充质干细胞治疗糖尿病心脏病研究进展及其机制

糖尿病心脏病(diabetic cardiomyopathy,DCM)患者心脏病变弥漫、病变程度严重,患病率与死亡率逐年上升,缺乏有效的治疗手段,找到其他的治疗途径已成为一项重要内容。有研究发现,间充质干细胞(mesenchymal stem cells,MSCs)作为一种具有多分化潜能的细胞,能够通过多种机制作用于DCM的病理改变,提高心脏射血分数、改善心室重塑,是一种富有前景的治疗手段,本文着重就DCM的发病机制、MSCs对DCM的治疗机制及效果做一综述,为MSCs在DCM治疗中的应用提供重要的临床前实验依据。     

间充质干细胞对新型冠状病毒肺炎免疫损伤潜在修复作用的研究进展

针对新型冠状病毒肆虐以及暂无特效药物治疗的情况,多地已开展间充质干细胞(MSCs)在新型冠状病毒感染重症救治方面的临床研究,在规范应用的前提下,经过严格的临床检验后,对若干重型患者进行治疗并取得了一定效果。MSCs能抑制免疫系统过度激活,通过改善微环境促进内源性修复、抑制肺部炎症的进展达到缓解呼吸窘迫症状的目的。本文就新型冠状病毒免疫损伤的发生机制、治疗现状以及MSCs在治疗新型冠状病毒感染的潜在治疗机制作一介绍。     

53例重症甲型H1N1流感临床分析

目的了解重症甲型H1N1流感的临床特点,探索其治疗方法。方法回顾性分析53例重症甲型H1N1流感患者的临床资料,总结其临床规律及特点。结果重症甲型H1N1流感好发于20～40岁,20例（37.74%）伴有各种基础疾病。51例（96.23%）有发热,且48例（90.57%）为首发症状,多伴随有畏寒、咳嗽、咳痰、乏力、胸闷和气急等症状。发病早期血常规检查白细胞及中性粒细胞多正常或下降;胸部影像学检查提示33例（62.26%）患者继发不同程度的支气管炎或肺炎。患者经奥司他韦或帕拉米韦抗病毒治疗及相应的抗感染、针对基础疾病治疗等,除2例患者自动出院外,余均痊愈出院。结论重症甲型H1N1流感起病急,早诊断、早期积极合理治疗,能改善预后。     

CD4^＋CD25^＋调节性T细胞与炎症性肠病

CD4＋CD25＋调节性T细胞（Treg）是一种有免疫抑制功能的T淋巴细胞,其在炎症性肠病（IBD）中的功能机制已成为近年免疫学和临床研究的热点。目前,Treg细胞新的表型和作用机制逐渐被大量的实验和研究证实。本文就Treg在IBD发病过程中的作用机理及益生菌对Treg功能的影响做一综述。     

Strategies to improve the effect of mesenchymal stem cell therapy on inflammatory bowel disease

Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis and is an idiopathic, chronic inflammatory disease of the colonic mucosa. The occurrence of IBD, causes irreversible damage to the colon and increases the risk of carcinoma. The routine clinical treatment of IBD includes drug treatment, endoscopic treatment and surgery. The vast majority of patients are treated with drugs and biological agents, but the complete cure of IBD is difficult. Mesenchymal stem cells (MSCs) have become a new type of cell therapy for the treatment of IBD due to their immunomodulatory and nutritional functions, which have been confirmed in many clinical trials. This review discusses some potential mechanisms of MSCs in the treatment of IBD, summarizes the experimental results, and provides new insights to enhance the therapeutic effects of MSCs in future applications.     

Mesenchymal stem cells targeting the GVHD

Acute graft-versus-host disease(GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues.About 35%—50% of hematopoietic stem cell transplant(HSCT) recipients will develop acute GVHD.It is associated with considerable morbidity and mortality,particularly in patients who do not respond to primary therapy,which usually consists of glucocorticoids(steroids).Most of the available second-line and third-line treatments for steroid-refractory acut...     

Could co‐transplantation of iPS cells derived hepatocytes and MSCs cure end‐stage liver disease?

Orthotopic liver transplantation is, to date, the only proven effective treatment for end-stage liver disease. However, it suffers from lack of donors and immunorejection. Here, we speculate that co-transplantation of induced pluripotent stem (iPS) cells derived hepatocytes and mesenchymal stem cells (MSCs) may offer an alternative way to treat patients with end-stage liver disease. Recently, progress on iPS cells, homogeneous differentiation of hepatocyte-like cells from embryonic stem cells (ESCs), and paracrine effects by MSCs highlight the possibility. Safe, efficient and rapid generation of iPS cells has been reliably produced by several experimental laboratories. Methods for highly efficient and homogeneous differentiation of ESCs into functional hepatocytes have been established as well. Moreover, paracrine effects by MSCs have been proven to play an important role in liver regeneration and repair, and the effects can be used as an enhancer for engraftment. All of these remarkable developments lead to this hypothesis which may offer a novel therapeutic strategy for treatment of patients with end-stage liver disease, though some issues about safety and efficacy need to be further guaranteed.     

Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: Role of secretome and exosomes

Over the last decades, mesenchymal stem cells (MSCs) have been extensively studied with regard to their potential applications in regenerative medicine. In rheumatic diseases, MSC-based therapy is the subject of great expectations for patients who are refractory to proposed treatments such as rheumatoid arthritis (RA), or display degenerative injuries without possible curative treatment, such as osteoarthritis (OA). The therapeutic potential of MSCs has been demonstrated in several pre-clinical models of OA or RA and both the safety and efficacy of MSC-based therapy is being evaluated in humans. The predominant mechanism by which MSCs participate to tissue repair is through a paracrine activity. Via the production of a multitude of trophic factors with various properties, MSCs can reduce tissue injury, protect tissue from further degradation and/or enhance tissue repair. However, a thorough in vivo examination of MSC-derived secretome and strategies to modulate it are still lacking. The present review discusses the current understanding of the MSC secretome as a therapeutic for treatment of inflammatory or degenerative pathologies focusing on rheumatic diseases. We provide insights on and perspectives for future development of the MSC secretome with respect to the release of extracellular vesicles that would have certain advantages over injection of living MSCs or administration of a single therapeutic factor or a combination of factors.     

Current understanding of mesenchymal stem cells in liver diseases

Liver diseases caused by various factors have become a significant threat to public health worldwide. Liver transplantation has been considered as the only effective treatment for end-stage liver diseases; however, it is limited by the shortage of donor organs, postoperative complications, long-term immunosuppression, and high cost of treatment. Thus, it is not available for all patients. Recently, mesenchymal stem cells (MSCs) transplantation has been extensively explored for repairing hepatic injury in various liver diseases. MSCs are multipotent adult progenitor cells originated from the embryonic mesoderm, and can be found in mesenchymal tissues including the bone marrow, umbilical cord blood, adipose tissue, liver, lung, and others. Although the precise mechanisms of MSC transplantation remain mysterious, MSCs have been demonstrated to be able to prevent the progression of liver injury and improve liver function. MSCs can self-renew by dividing, migrating to injury sites and differentiating into multiple cell types including hepatocytes. Additionally, MSCs have immune-modulatory properties and release paracrine soluble factors. Indeed, the safety and effectiveness of MSC therapy for liver diseases have been demonstrated in animals. However, pre-clinical and clinical trials are largely required to confirm its safety and efficacy before large scale clinical application. In this review, we will explore the molecular mechanisms underlying therapeutic effects of MSCs on liver diseases. We also summarize clinical advances in MSC-based therapies.     

Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy

Inflammatory bowel disease(IBD), consisting primarily of ulcerative colitis and Crohn's disease, is a group of debilitating auto-immune disorders, which also increases the risk of colitis-associated cancer. However, due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs(e.g., approximately 30% non-responders to anti-TNFα agents), and related serious side effects, about half of all IBD patients(in millions) turn to alternative treatment options. In this regard, mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis. However, despite the increasing clinical realization of the significance of the concept of mucosal healing, its regulation and means of therapeutic targeting remain largely unclear. Here, stemcell therapy, which uses hematopoietic stem cells or mesenchymal stem cells, remains a promising option. Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells. The overreaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process. Moreover, by differentiating into the mature intestinal epithelial cells, the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction, the root cause of the IBD. In this article, we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient's quality of life.     

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.