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诱导型多能干细胞技术是一种通过新的体细胞重编程，将组织细胞转化为可多向分化的细胞即干细胞的技术。目前已将4种转录因子导入人体皮肤纤维母细胞，并首次成功诱导出诱导型多能干细胞。此项技术不但可以建立神经系统疾病动物模型，用于发病机制和致病基因的研究，而且可以开展移植研究，验证疗效及筛选药物。

目的探讨诱导多能干细胞（iPSc）移植对急性心肌梗死小鼠心脏Q-T间期的影响,并对移植的安全性、有效性进行初步评估。方法建立小鼠心肌梗死模型并将其随机分为急性心肌梗死组（AMI）,急性心肌梗死＋生理盐水组（AMI＋NS）,急性心肌梗死＋iPSc组（AMI＋iPSc）,急性心肌梗死＋成纤维细胞组（AMI＋Fb）,每组15只,同时取20只小鼠设为正常对照组（NCG）。分别于移植iPSc后5min及1、2、3周,应用BL-420生物机能系统检测小鼠体表心电图肢体Ⅱ导联Q-T间期的变化。移植后2周采用免疫组化染色检测各组小鼠心肌缝隙连接蛋白43（Cx-43）的表达,应用Image-ProPlus软件进行半定量分析。结果与AMI组和AMI＋Fb组比较,移植2周后AMI＋iPSc组小鼠体表心电图Ⅱ导联Q-T间期明显缩短,梗死心肌Cx-43表达明显增加（P〈0.05）,而前两组间比较差异无统计学意义。移植后3周与2周时呈现相似的变化趋势。结论 iPSc移植可明显缩短心肌梗死小鼠延长的Q-T间期,并使小鼠梗死心肌Cx-43的表达增加,而成纤维细胞移植的小鼠中则未出现此现象。

Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells （CSCs） similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC hetero- geneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells （iPSCs）, and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice （GMP） facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

Osteoarthritis（OA）is a degenerative joint disorder commonly encountered in clinical practice,and is the leading cause of disability in elderly people.Due to the poor self-healing capacity of articular cartilage and lack of specific diagnostic biomarkers,OA is a challenging disease with limited treatment options.Traditional pharmacologic therapies such as acetaminophen,non-steroidal anti-inflammatory drugs,and opioids are effective in relieving pain but are incapable of reversing cartilage damage and are frequently associated with adverse events.Current research focuses on the development of new OA drugs（such as sprifermin/recombinant human fibroblast growth factor-18,tanezumab/monoclonal antibody againstβ-nerve growth factor）,which aims for more effectiveness and less incidence of adverse effects than the traditional ones.Furthermore,regenerative therapies（such as autologous chondrocyte implantation（ACI）,new generation of matrix-induced ACI,cell-free scaffolds,induced pluripotent stem cells（iPS cells or iPSCs）,and endogenous cell homing）are also emerging as promising alternatives as they have potential to enhance cartilage repair,and ultimately restore healthy tissue.However,despite currently available therapies and research advances,there remain unmet medical needs in the treatment of OA.This review highlights current research progress on pharmacologic and regenerative therapies for OA including key advances and potential limitations.

Metabolism is vital to every aspect of cell function, yet the metabolome of induced pluripotent stem cells （iPSCs） remains largely unexplored. Here we report, using an untargeted metabolomics approach, that human iPSCs share a pluripotent metabolomic signature with embryonic stem cells （ESCs） that is distinct from their parental cells, and that is characterized by changes in metabolites involved in cellular respiration. Examination of cellular bioenergetics corroborated with our metabolomic analysis, and demonstrated that somatic cells convert from an oxidative state to a glycolytic state in pluripotency. Interestingly, the bioenergetics of various somatic cells correlated with their repro- gramming efficiencies. We further identified metabolites that differ between iPSCs and ESCs, which revealed novel metabolic pathways that play a critical role in regulating somatic cell reprogramming. Our findings are the first to globally analyze the metabolome of iPSCs, and provide mechanistic insight into a new layer of regulation involved in inducing pluripotency, and in evaluating iPSC and ESC equivalence.

Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya Yamanaka and Sir John Gurdon, there is an increasing interest in the induced pluripotent stem （iPS） cells and reprograming technologies in medical science. While iPS cells are expected to open a new era providing enormous opportunities in biomedical sciences in terms of cell therapies and regenerative medicine, safety-related concerns for iPS cell-based cell therapy should be resolved prior to the clinical application of iPS cells. In this review, the pre-clinieal investigations of cell therapy for spinal cord injury （SCI） using neural stem/progenitor cells derived from iPS cells, and their safety issues in vivo, are outlined. We also wish to discuss the strategy for the first human trails of iPS cell-based cell therapy for SCI patients.

Pluripotent stem cells, like embryonic stem cells （ESCs）, have specialized epigenetic landscapes, which are important for pluripotency maintenance. Transcription factor-mediated generation of induced pluripotent stem cells （iPSCs） requires global change of somatic cell epigenetic status into an ESC-like state. Accumulating evidence indicates that epigenetic mechanisms not only play important roles in the iPSC generation process, but also affect the properties of reprogrammed iPSCs. Understanding the roles of various epigenetic factors in iPSC generation contributes to our knowledge of the reprogramming mechanisms.

Dear Editor, Neurological disorder is one of the greatest threats to public health according to the World Health Organi- zation. Because neurons have little or no regenerative capacity, conventional therapies for neurological disor- ders yielded poor outcomes. While the introduction of exogenous neural stem cells or neurons holds promise, many challenges still need to be tackled, including cell resource, delivery strategy, cell integration and cell maturation. Reprogramming of fibroblasts into induced pluripotent stem cells or directly into desirable neuronal cells by transcription factors （TFs） or small molecules can solve some problems, but other issues remain to be addressed, including safety, conversion efficiency and epigenetic memory .

Generation of induced pluripotent stem cells （iPSCs） has opened new avenues for the investigation of heart diseases, drug screening and potential autologous cardiac regeneration. However, their application is hampered by inefficient cardiac differentiation, high interline variability, and poor maturation of iPSC-derived cardiomyocytes （iPS-CMs）. To identify efficient inducers for cardiac differentiation and maturation of iPSCs and elucidate the mechanisms, we systematically screened sixteen cardiomyocyte inducers on various mnrine （m） iPSCs and found that only ascorbic acid （AA） consistently and robustly enhanced the cardiac differentiation of eleven lines including eight without spontaneous cardiogenic potential. We then optimized the treatment conditions and demonstrated that differentiation day 2-6, a period for the specification of cardiac progenitor cells （CPCs）, was a critical time for AA to take effect. This was further confirmed by the fact that AA increased the expression of cardiovascular but not mesodermal markers. Noteworthily, AA treatment led to approximately 7.3-fold （miPSCs） and 30.2-fold （human iPSCs） augment in the yield of iPS-CMs. Such effect was attributed to a specific increase in the proliferation of CPCs via the MEK-ERK1/2 pathway by promoting collagen synthesis. In addition, AA-induced cardiomyocytes showed better sarcomeric organization and enhanced responses of action potentials and calcium transients to p-adrenergic and muscarinic stimulations. These findings demonstrate that AA is a suitable cardiomyocyte inducer for iPSCs to improve cardiac differentiation and maturation simply, universally, and efficiently. These findings also highlight the importance of stimulating CPC proliferation by manipulating extracellular microenvironment in guiding cardiac differentiation of the pluripotent stem cells.