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| 1 | Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy显示文摘Mesenchymal stem cells(MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses. | Justin D Glenn Katharine A Whartenby | 2014 | World Journal of Stem Cells2014，6，5： | 55 |
| 2 | WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Umbilical cord-derived mesenchymal stem cells:Their advantages and potential clinical utility显示文摘Human umbilical cord(UC)is a promising source of mesenchymal stem cells(MSCs).Apart from their prominent advantages,such as a painless collection procedure and faster self-renewal,UC-MSCs have shown the ability to differentiate into three germ layers,to accumulate in damaged tissue or inflamed regions,to promote tissue repair,and to modulate immune response.There are diverse protocols and culture methods for the isolation of MSCs from the various compartments of UC,such as Wharton’s jelly,vein,arteries,UC lining and subamnion and perivascular regions.In this review,we give a brief introduction to various compartments of UC as a source of MSCs and emphasize the potential clinical utility of UC-MSCs for regenerative medicine and immunotherapy. | Tokiko Nagamura-Inoue Haiping He | 2014 | World Journal of Stem Cells2014，6，2： | 46 |
| 3 | Mesenchymal stem cells: Molecular characteristics and clinical applications显示文摘Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues. Their ease of isolation and ex vivo expansion combined with their immunoprivileged nature has made these cells popular candidates for stem cell therapies. These cells have the potential to alter disease pathophysiology through many modalities including cytokine secretion, capacity to differentiate along various lineages, immune modulation and direct cell-cell interaction with diseased tissue. Here we first review basic features of MSC biology including MSC characteristics in culture, homing mechanisms, differentiation capabilities and immune modulation. We then highlight some in vivo and clinical evidence supporting the therapeutic roles of MSCs and their uses in orthopedic, autoimmune, and ischemic disorders. | Farbod Rastegar Deana Shenaq Eric R Wagner Stephanie H Kim Russell R Reid Hue H Luu Rex C Haydon | 2010 | World Journal of Stem Cells2010，2，4： | 35 |
| 4 | Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?显示文摘Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms. | Ann De Becker Ivan Van Riet | 2016 | World Journal of Stem Cells2016，8，3： | 37 |
| 5 | Adipose-derived stromal cells: Their identity and uses in clinical trials, an update显示文摘In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc. ). Apart from a phase Ⅲ trial on the treatment of fistula,most of these are in phaseⅠand use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use. | Louis Casteilla Valérie Planat-Benard Patrick Laharrague Béatrice Cousin | 2011 | World Journal of Stem Cells2011，3，4： | 31 |
| 6 | Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts显示文摘Bone is a dynamic tissue that is constantly renewed by the coordinated action of two cell types, i.e., the bone-resorbing osteoclasts and the bone-forming osteoblasts. However, in some circumstances, bone regeneration exceeds bone self repair capacities. This is notably often the case after bone fractures, osteolytic bone tumor surgery, or osteonecrosis. In this regard,bone tissue engineering with autologous or allogenic mesenchymal stem cells(MSCs) is been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre-clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial to optimize MSC-bone therapy. In this review, we first present the important growth factors that stimulate osteoblastogenesis. Then we review the main transcription factors that modulate osteoblast differentiation, and the microRNAs(miRs)that inhibit their expression. Finally, we also discuss articles dealing with the use of these factors and miRs in the development of new bone MSC therapy strategies. We particularly focus on the studies using human MSCs, since significant differences exist between osteoblast differentiation mechanisms in humans and mice for instance. | Maya Fakhry René Buchet David Magne Eva Hamade Bassam Badran | 2013 | World Journal of Stem Cells2013，5，4： | 32 |
| 7 | WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Mesenchymal stem cells in the treatment of spinal cord injuries:A review显示文摘With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord,the cure for paralysis remains elusive.Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI.R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results.An array of mesenchymal stem cells(MSCs)from various sources with novel and promising strategies are being developed to improve function after SCI.In this review,we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI.We will discuss the progress of MSCs application in research,focusing on the neuroprotective properties of MSCs.Finally,we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI. | Venkata Ramesh Dasari Krishna Kumar Veeravalli Dzung H Dinh | 2014 | World Journal of Stem Cells2014，6，2： | 32 |
| 8 | Adipose-derived stromal cell in regenerative medicine:A review显示文摘The application of appropriate cell origin for utilizing inregenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells(ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage. | Reza Tabatabaei Qomi Mohsen Sheykhhasan | 2017 | World Journal of Stem Cells2017，9，8： | 33 |
| 9 | Role ofthe IncRNA-p53 regulatory network in cancer显示文摘 | Ali Zhang Min Xu Yin-Yuan Mo | 2014 | Journal of Molecular Cell Biology2014，8，3： | 29 |
| 10 | Immune regulatory properties of multipotent mesenchymal stromal cells:Where do we stand?显示文摘Multipotent mesenchymal stromal cells (MSC) can be isolated and efficiently expanded from almost every single body tissue and have the ability of self-renewal and differentiation into various mesodermal cell lineages. Moreover, these cells are considered immunologically privileged, related to a lack of surface expression of costimulatory molecules required for complete T cell activation. Recently, it has been observed that MSC are capable of suppressing the immune response by inhibiting the maturation of dendritic cells and suppressing the function of T lymphocytes, B lymphocytes and natural killer cells in autoimmune and inflammatory diseases as a new strategy for immunosuppression. The understanding of immune regulation mechanisms by MSC is necessary for their use as immunotherapy in clinical applications for several diseases. | ênio José Bassi Carlos Alberto Mayora Aita Niels Olsen Saraiva Camara | 2011 | World Journal of Stem Cells2011，3，1： | 27 |
| 11 | The p53/miR-34 axis in development and disease显示文摘肿瘤 suppressor p53 是在人的癌症的最经常变异的基因之一。MicroRNAs (miRNAs ) 是在 post-transcriptional 水平上调整基因表示的小 non-proteincoding RNA。最近, p53 调整几 miRNAs 的 theexpression,这被显示出,从而代表 p53 发信号的重要机制。几个独立人士作为最流行的导致 p53 的 miRNAs 学习 miR-34 家庭的 identifiedthe 成员。miR-34s 经常是在 tumorentities 的变化的 silenced,建议他们是重要肿瘤 suppressors。确实, miR-34s 的宫外的表示禁止增长,对各种各样的癌症房间实体的间充质的转变,移植,侵略,和转移上皮。而且, miR-34 的 deliveryor 重新表示在癌症老鼠模型导致肿瘤生长和转移的著名压抑,并且可以 thereforerepresent 为未来癌症治疗学的有效策略。除他们在癌症的关键函数以外, themiR-34 家庭的成员也在精子发生,干细胞区别, neuronal 开发,老化,和 cardiovascularfunctions 起重要作用。因而, miR-34 也在各种各样的非癌的疾病被含有,例如大脑混乱,骨质疏松症,和心血管的复杂并发症。 | Matjaz Rokavec Huihui Li Longchang Jiang and Heiko Hermeking | 2014 | Journal of Molecular Cell Biology2014，8，3： | 27 |
| 12 | Epithelial-mesenchymal transition- activating transcription factors- multifunctional regulators in cancer显示文摘The process of epithelial to mesenchymal transition(EMT), first noted during embryogenesis, has also been reported in tumor formation and leads to the development of metastatic growth. It is a naturally occurring process that drives the transformation of adhesive,non-mobile epithelial like cells into mobile cells with a mesenchymal phenotype that have ability to migrate to distant anatomical sites. Activating complex network of embryonic signaling pathways, including Wnt, Notch,hedgehog and transforming growth factor-β pathways,lead to the upregulation of EMT activating transcription factors, crucial for normal tissue development and maintenance. However, deregulation of tightly regulated pathways affecting the process of EMT has been recently investigated in various human cancers. Given the critical role of EMT in metastatic tumor formation,better understanding of the mechanistic regulation provides new opportunities for the development of potential therapeutic targets of clinical importance. | Minal Garg | 2013 | World Journal of Stem Cells2013，5，4： | 26 |
| 13 | p53 modifications:exquisite decorations ofthe powerful guardian显示文摘The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell fate decisions.Among the multiple layers of mechanisms controlling p53 function,posttranslational modifications (PTMs) represent an efficient and precise way.Major p53 PTMs include phosphorylation,ubiquitination,acetylation,and methylation.Meanwhile,other PTMs like sumoylation,neddylation,O-GlcNAcylation,adenosine diphosphate (ADP)-ribosylation,hydroxylation,and p-hydroxybutyrylation are also shown to play various roles in p53 regulation.By independent action or interaction,PTMs affect p53 stability,conformation,localization,and binding partners.Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases,especially in cancers.This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation. | Yanqing Liu Omid Tavana Wei Gu | 2019 | Journal of Molecular Cell Biology2019，11，7： | 24 |
| 14 | Endothelial progenitor cells in cardiovascular diseases显示文摘Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome. | Poay Sian Sabrina Lee Kian Keong Poh | 2014 | World Journal of Stem Cells2014，6，3： | 22 |
| 15 | Mutant p53 in colon cancer显示文摘The accumulation of genetic alterations in driver genes is responsible for the development and malignant progression of colorectal cancer. Comprehensive genome analyses have revealed the driver genes, including APC, KRAS, TGFBR2, and TP53, whose mutations are frequently found in human colorectal cancers. Among them, the p53 mutation is found in ~60% of colorectal cancers, and a majority of mutations are missense-type at ‘hot spots’, suggesting an oncogenic role of mutant p53 by ‘gain-of-function’ mechanisms. Mouse model studies have shown that one of these missense-type mutations, p53 R270H (corresponding to human R273H), causes submucosal invasion of intestinal tumors, while the loss of wild-type p53 has a limited effect on the invasion process. Furthermore, the same mutant p53 promotes metastasis when combined with Kras activation and TGF-β suppression. Importantly, either missense-type p53 mutation or loss of wild-type p53 induces NF-κB activation by a variety of mechanisms, such as increasing promoter accessibility by chromatin remodeling, which may contribute to progression to epithelial–mesenchymal transition. These results indicate that missense-type p53 mutations together with loss of wild-type p53 accelerate the late stage of colorectal cancer progression through the activation of both oncogenic and inflammatory pathways. Accordingly, the suppression of the mutant p53 function via the inhibition of nuclear accumulation is expected to be an effective strategy against malignant progression of colorectal cancer. | Mizuho Nakayama Masanobu Oshima | 2019 | Journal of Molecular Cell Biology2019，11，4： | 22 |
| 16 | GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity显示文摘Gasdermin B (GSDMB) has been reported to be associated with immune diseases in humans, but the detailed molecular mechanisms remain unsolved. The N-terminus of GSDMB by itself, unlike other gasdermin family proteins, does not induce cell death. Here, we show that GSDMB is highly expressed in the leukocytes of septic shock patients, which is associated with increased release of the gasdermin D (GSDMD) N-terminus. GSDMB expression and the accumulation of the N-terminal fragment of GSDMD are induced by the activation of the non-canonical pyroptosis pathway in a human monocyte cell line. The downregulation of GSDMB alleviates the cleavage of GSDMD and cell death. Consistently, the overexpression of GSDMB promotes GSDMD cleavage, accompanied by increased LDH release. We further found that GSDMB promotes caspase-4 activity, which is required for the cleavage of GSDMD in non-canonical pyroptosis, by directly binding to the CARD domain of caspase-4. Our study reveals a GSDMB-mediated novel regulatory mechanism for non-canonical pyroptosis and suggests a potential new strategy for the treatment of inflammatory diseases. | Qin Chen Peiliang Shi Yufang Wang Dayuan Zou Xiuwen Wu Dingyu Wang Qiongyuan Hu Yujie Zou Zan Huang Jianan Ren Zhaoyu Lin Xiang Gao | 2019 | Journal of Molecular Cell Biology2019，11，6： | 22 |
| 17 | Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation显示文摘Disrupted mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation are often associated with macrophage pyroptosis. It remains unclear how these forms of mitochondrial dysfunction relate to inflammasome activation and gasdermin-D (Gsdmd) cleavage, two central steps of the pyroptotic process. Here, we also found MMP collapse and ROS generation induced by Nlrp3 inflammasome activation as previous studies reported. The elimination of ROS alleviated the cleavage of Gsdmd, suggesting that Gsdmd cleavage occurs downstream of ROS release. Consistent with this result, hydrogen peroxide treatment augmented the cleavage of Gsdmd by caspase-1. Indeed, four amino acid residues of Gsdmd were oxidized under oxidative stress in macrophages. The efficiency of Gsdmd cleavage by inflammatory caspase-1 was dramatically reduced when oxidative modification was blocked by mutation of these amino acid residues. These results demonstrate that Gsdmd oxidation serves as a de novo mechanism by which mitochondrial ROS promote Nlrp3 inflammasome-dependent pyroptotic cell death. | Yufang Wang Peiliang Shi Qin Chen Zan Huang Dayuan Zou Jingzi Zhang Xiang Gao Zhaoyu Lin | 2019 | Journal of Molecular Cell Biology2019，11，12： | 23 |
| 18 | TRIM4 modulates type I interferon induction and cellular antiviral response by targeting RIG-I for K63-1inked ubiquitination显示文摘RIG-I 是认出病毒的 RNA 的不同种类的一个枢轴的细胞质的传感器。这识别导致抄写因素 NF-B 和 IRF3,它协作导致打的 activationof 我干扰素(IFN ) 和天生的抗病毒的 response.In 这研究,我们作为 RIG-I-mediated IFN 的一个积极管理者识别了整齐的家庭蛋白质 TRIM4 感应。Overexpressionof TRIM4 加强了 IRF3 和 NF-B 的被触发病毒的激活,以及 IFN- 正式就职,而 TRIM4had 相反的效果击倒。机械学地, TRIM4 与 RIG-I 联系并且为连接 K63 的 polyubiquitination 指向它。我们 TRIM4 是由调停的导致病毒的 IFN 正式就职小径的一个重要管理者的 findingsdemonstrate 为 K63-linkedubiquitination 的 RIG-I。 | Jie Yan Qi Li Ai-Ping Mao Hong-Bing Shu | 2014 | Journal of Molecular Cell Biology2014，8，2： | 21 |
| 19 | Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration显示文摘Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry. | Oleh Andrukhov Christian Behm Alice Blufstein Xiaohui Rausch-Fan | 2019 | World Journal of Stem Cells2019，11，9： | 21 |
| 20 | Use of bone morphogenetic proteins in mesenchymal stemcell stimulation of cartilage and bone repair显示文摘The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair. | Sonia Scarfì | 2016 | World Journal of Stem Cells2016，8，1： | 21 |
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