Stem cells and blastema cells

Recently much effort has resulted in papers on how stem cells can be generated from adult tissues in mice, but the salamanders do this routinely. Salamanders can regenerate most of their body parts, such as limbs, eyes, jaw, brain (and spinal cord), heart, etc. Regeneration in salamanders starts by dedifferentiation of the terminally differentiated tissues at the site of injury. The dedifferentiated cells can then differentiate to reconstitute the lost tissues. This transdifferentiation in an adult animal is unprecedented among vertebrates and does not involve recruitment of stem cells. One of the ideas is that such reprogramming of terminally differentiated cells might involve mechanisms that are similar to the maintenance of embryonic stem cells. In the stem cell field much emphasis has been recently given to the reprogramming of adult cells (such as skin fibroblasts) to revert to ES or pluripotent stem cells. It is our conviction that generation of dedifferentiated cells in salamanders and stem cells, such as the ones seen in repair in mammals share molecular signatures. This mini review will discuss these issues and ideas that could unite the stem cell biology with the classical regeneration models.     

Purkyn? cells and Betz cells

J.E. Purkyn? was the first to discover, by achromatic microscopy of stained and fixed as well as of fresh material, that animal tissues in general, and those of the central nervous system in particular, are made up of cells, as are those of plants. His discoveries laid the foundations of modern research on the ultrastructure and biophysies of the cerebellar neurons which bear his name, as well as on other types of neurons, in vitro as well as in vivo.     

Communications between bone cells and hematopoietic stem cells

The skeletal system, while characterized by a hard tissue component, is in fact an extraordinarily dynamic system, with disparate functions ranging from structural support, movement and locomotion and soft-organ protection, to the maintenance of calcium homeostasis. Amongst these functions, it has long been known that mammalian bones house definitive hematopoiesis. In fact, several data demonstrate that the bone microenvironment provides essential regulatory cues to the hematopoietic system. In particular, interactions between the bone-forming cells, or osteoblasts, and the most primitive Hematopoietic Stem Cells (HSC) have recently been defined. This review will focus mainly on the role of osteoblasts as HSC regulatory cells, discussing the signaling mechanisms and molecules currently thought to be involved in their modulation of HSC behavior. We will then review additional cellular components of the HSC niche, including endothelial cells and osteoclasts. Finally, we will discuss the potential clinical implications of our emerging understanding of the complex HSC microenvironment.     

人羊膜上皮细胞和胚胎干细胞

人胚胎干细胞有着巨大的医学应用前景,但人胚胎干细胞要求的生长条件很高,体外很难模拟其生长的体内环境,因此控制人胚胎干细胞的生长常不理想,而使用鼠胚胎成纤维细胞(MEF)作为滋养层则存在动物源性污染的问题。该文阐述人羊膜上皮细胞(HAEC)的特点及其作为滋养层培养胚胎干细胞的现状,并探讨基因组DNA甲基化修饰在胚胎干细胞分化过程中的作用,为建立更优化的培养系统提供依据。     

Relationships between stem cells and cancer stem cells

Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. These rare transformed stem cells may drive the process of tumorigenesis due to their potential for self renewal. There are important ramifications for clinical cancer treatment if the growth of solid tumors is at least partially dependent on a cancer stem cell population. In the cancer stem cell model, tumor recurrence may be due to the non-targeted stem cell compartment repopulating the tumor. If cancer stem cells can be prospectively identified and isolated, it should be possible to identify therapies that will selectively target these cells.     

Dendritic cells and innate defense against tumor cells

Tumor growth results from a delicate balance between intrinsic dysregulation of oncogenes, tumor suppressor and stability genes counteracted by extrinsic defenses composed of immune cells shaping tumor immunogenicity. Although immune subversion might be the ultimate outcome of this process, a complex network of cellular interactions take place eventually leading to tumor specific cognate immune responses. The links between innate and cognate antitumor immunity eliciting protective T cell responses are instigated by cytokines, chemokines and damage associated molecular patterns. The intricate differentiation pathway whereby dendritic cells could undergo an efficient maturation program in the tumor microenvironment appears crucial. We will discuss the role of innate effectors and cancer therapies in the process of defense against tumor cells.     

Th17细胞和Treg细胞与动脉粥样硬化

动脉粥样硬化从脂质条纹的形成到更复杂的病变和斑块破裂的进程是由多种不同类型的细胞和细胞因子网络共同参与作用的,其中最主要的是Th17细胞和Treg细胞及它们分泌的细胞因子。大量研究显示,Th17细胞对动脉粥样硬化的作用仍存在争议,但大部分研究仍认为其具有促动脉粥样硬化的作用。Treg细胞具有抗动脉粥样硬化的作用,Th17／Treg平衡对动脉粥样硬化的发生和发展具有重要的调节作用。本文将对Th17细胞、Treg细胞的生物学特性以及Th17细胞、Treg细胞和Th17／Treg平衡对动脉粥样硬化影响的最新研究进展做一综述。     

Transfer cells and nematode induced giant cells inHelianthemum

Summary The morphology of wall ingrowths in xylem and phloem transfer cells inHelianthemum is different. It is possible to use nematode infection to induce the formation of giant cells which abut both xylem and phloem elements to test whether ingrowth morphology is controlled by the solutes presumed to be transported across the plasmalemma of the cells. This experiment has been done and it is found that although wall ingrowths develop against both xylem and phloem, the giant cells exhibit only the ingrowth structure characteristic of xylem transfer cells.     

pH regulation in spread cells and round cells

The aim of this work was to characterize the changes in pH regulation that lead to increased intracellular pH (pHi) in well-spread cells on tissue culture plastic relative to cells on a nonadhesive surface. Bicarbonate was not required for maintenance of a control steady state pHi or of the difference in pHi between round and spread cells. In the absence of bicarbonate, lowering the sodium content of the medium led to decreased pHi and elimination of the difference between round and spread cells. In the presence or absence of bicarbonate, adding ethylisopropyl amiloride lowered pHi and eliminated the difference between round and spread cells. Measurements of recovery from acute acidification in the absence of bicarbonate confirmed that Na+/H+ exchange was enhanced in spread cells. However, recovery from both acidification and alkalinization in the presence of bicarbonate showed that bicarbonate-dependent recovery in both directions, most likely due to sodium-dependent and -independent HCO3-/Cl- exchangers, was also stimulated in spread cells. We conclude that Na+/H+ exchange has a primary role in determining steady state pHi in 3T3 cells in serum and is responsible for the lower pHi in round cells. Bicarbonate-dependent pH regulatory mechanisms are also inhibited in round cells.     

MicroRNAs,stem cells and cancer stem cells

This review discusses the various regulatory charac-teristics of microRNAs that are capable of generating widespread changes in gene expression via post translational repression of many mRNA targets and control self-renewal, differentiation and division of cells. It controls the stem cell functions by controlling a wide range of pathological and physiological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis and metastasis. Through either mRNA cleavage or translational repression, miRNAs alter the expression of their cognate target genes; thereby modulating cellular pathways that affect the normal functions of stem cells, turning them into cancer stem cells, a likely cause of relapse in cancer patients. This present review further emphasizes the recent discoveries on the functional analysis of miRNAs in cancer metastasis and implications on miRNA based therapy using miRNA replacement or anti-miRNA technologies in specific cancer stem cells that are required to establish their efficacy in controlling tumorigenic potential and safe therapeutics.     

Phenotype and hybrids between lymphoid cells and rat hepatoma cells

Subtetraploid rat hepatoma cells were fused with diploid or tetraploid lymphoid cells of various origins. All hybrid cells, analysed 28 h to 26 days after fusion, expressed basal and steroid-induced activities of the liver-specific enzyme tyrosine aminotransferase within the range given by the parental hepatoma cell line. Only the rat enzyme was produced in the hybrids. This was true, irrespective of the gene dosage of the lymphoid partner cell and of the presence of human X chromosomes. In contrast, the lymphoid phenotype, as monitored by production of kappa light chains specified by the diploid and tetraploid lymphoid partner cells, was totally suppressed within 72 h after fusion. No difference in phenotypic expression was observed, whether the hybrid cells were grown as monolayer or as suspension cultures.     

Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells

Naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) suppress proliferation of CD4(+)CD25(-) effector T cells (Teffs) by mechanisms that are not well understood. We have previously demonstrated a novel mechanism of Treg suppression, i.e. interference with extracellular redox remodeling that occurs during activation of T cells by dendritic cells. In this study, we demonstrate that Treg-mediated redox perturbation is antigen-dependent but not antigen-specific, is CTLA-4-dependent, and requires cell-cell contact. Furthermore, we show that Tregs use multiple strategies for extracellular redox remodeling, including diminished GSH synthesis in dendritic cells via decreased expression of γ-glutamylcysteine synthetase, the limiting enzyme for GSH synthesis. Tregs also consume extracellular cysteine and partition it more proficiently to the oxidation product (sulfate), whereas Teffs divert more of the cysteine pool toward protein and GSH synthesis. Tregs appear to block GSH redistribution from the nucleus to the cytoplasm in Teffs, which is abrogated by the addition of exogenous cysteine. Together, these data provide novel insights into modulation of sulfur-based redox metabolism by Tregs, leading to suppression of T cell activation and proliferation.