Immunoregulatory function of mesenchymal stem cells

Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non-mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA-incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno-mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell-to-cell interactions, but also by environmental factors shaping their phenotype and functions.     

Influences of the pia mater on the precursors of nerve cells

Summary In the developing cerebellum of 8-day old rats surgical lesions were made. During regeneration of the cerebellum the pia mater was found to penetrate inside the neural tissue. Partially differentiated Purkinje cells and granule cells, that were in close contact with the pial cells, were found atrophied. When the profilerative cells of external granular layer came into contact with the pial cells, they were reduced to a primitive type of epitheloid cells. In this instance epithelio-mesenchymal interaction was found deleterious to the precursors of neurons. However, when the epithelioid cells were freed from the contact with the pial cells by intervening basement membrane, they differentiated into ependymal cells. Such ependymal cells gave rise to small as well as large new ventriculer structures, and structures resembling chorioid plexus.This research was supported by NIH Research Grant NS08817-03. Acknowledgements are due to Sheila Anderson for histology and to Donna Whitehurst for photographic work.     

干细胞若干定义的相关探讨

背景：近10年来干细胞研究所取得的巨大进展,不仅影响和促进了生物学及其相关基础科学,而且还在医学、药物开发、农业等许多领域得到广泛的应用,目前已成为研究的热点问题。 目的：在干细胞的定义上还存在一些需要探讨的问题,明确定义将有利于干细胞研究的快速发展。 方法：回顾干细胞的发展和概念提出,特别是通过中英文权威定义的比较,提出作者的看法。 结果与结论：干细胞的定义上还存在一些问题值得探讨,特别是一些中英文表述不同影响了理解。例如,“多能干细胞”对应译成两个单词：Pluripotent Stem Cell和Multipotent Stem Cell,然而Pluripotent和Multipotent两个单词的英文意义不同。为了学术交流和沟通,作者提出将Pluripotent Stem Cell称为“万能干细胞”,而保留Multipotent Stem Cell为“多能干细胞”的定义。以上结论供广大同仁探讨,以利于抛砖引玉。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Genetic aspects of the immunomodulationg action of interferon

Laboratory of Antiviral Immunity, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. D. Solov'ev.) Translated from Byulleten' Éksperimentl'noioi Biologii i Meditsiny, Vol. 105, No. 4, pp. 459–461, April, 1988.     

Identification of a CD8α Dendritic Cell Subpopulation in Rat Spleen and Evaluation of Its OX-62 Expression

Rat spleen DC and bone marrow-derived DC were isolated and characterized by morphology and flow cytometry. We found a CD8α⁺ DC subpopulation representing 19–48% (27.4 ± 12.0) of total spleen DC. The OX-62 expression on total spleen DC was 41–59% (51.8 ± 7.5). Myeloid bone marrow-derived DC were negative for CD8α and OX-62. We demonstrated the coexpression of CD8α and OX-62 molecules, at least in a portion CD8α⁺ spleen DC. Both CD8α⁺ and CD8α⁻ spleen DC subpopulations separated by MACS were able to induce an in vivo primary immune response to OVA. The immune response induced by the CD8α⁻ DC subpopulation was higher (P < 0.05). We identified a CD8α⁺ DC subpopulation in rat spleen less effective in inducing an immune response than CD8α⁻ DC. Moreover, our results suggest the presence of DC subpopulations with different lineages in DC preparations based on OX-62 expression.     

Accessory phenotype and function of macrophages induced by cyclic adenosine monophosphate

Mature macrophages (Mph) differentiated in culture from normal human peripheral blood monocytes (Mo) exhibit low activity as accessory cells (antigen-presenting cells) in T lymphocyte stimulation. A test system was established based on mitogenicity to quantitate the accessory activity of Mph-derived cells and to follow its changes for several days. The system used accessory cells treated with the oxidative mitogen, sodium periodate. The cells were subsequently co-cultured with pooled human lymphocytes from a cryopreserved stock. DNA synthesis in these cells was used as an indicator of accessory activity. Mph could be converted within 5-6 days into highly active accessory cells if a continuous stimulus of exogenously added dibutyryl cyclic AMP (db-cAMP) was provided. Mph treated by db-cAMP retained a high degree of HLA-DR expression but typical Mph markers such as non-specific esterase, phagocytosis, and expression of Fc-receptors were down-regulated. Acid phosphatase and myeloperoxidase underwent only slight changes, while the monocyte marker 5'-nucleotidase remained undetectable. Morphologically, the cells rounded up and developed veils and dendritiform elongations. In contrast to dendritic cells, Mph-derived accessory cells retained the CD14 antigen characteristic of monocytes and Mph. It is concluded that Mph are able to respond to exogenous stimuli and to convert into a highly active accessory cell. This contrasts to the well-known state of the 'activated Mph' with respect to markers and function. Both states appear to be antagonistically controlled by intracellular second messengers, as the accessory cell phenotype is positively correlated with intracellular cyclic AMP increase, whereas Mph activation correlates with cyclic GMP increase.     

Human Osteogenic Sarcoma: Fine Structure of the Osteoblastic Type

The fine structure of representative regions of 13 osteoblastic osteogenic sarcomas was studied. These regions contained four morphologically distinguishable subtypes of osteoblastlike cells. In addition, fibroblastlike and chondroblastlike cells were present, along with multinucleated giant cells, leukocytes, macrophagelike cells, and small populations of histogenetically unclassifiable (but probably neoplastic) cells.

The morphologic evidence was compatible with the view that the variations in appearance among the subgroups of osteobl astlike cells reflected differences in maturation and differentiation of these cells. In at least one subgroup, the morphologic findings suggested that the ceils were capable of manufacturing a secretory product. The multinucleated giant cells occurring in genuine tumor areas appeared to be closely related to neoplastic osteoblasts.

The presence of chondroblastlike cells in the tissues illustrates that cells with a diverging differentiation can occur in an osteoblast-dominated cell population. This agrees with the view that the neoplastic cells originate from a mesenchymal stem cell with potential for multifaceted differentiation.     

Trypanosoma cruzi calreticulin: In vitro modulation of key immunogenic markers of both canine tumors and relevant immune competent cells

Recombinant calreticulin from Trypanosoma cruzi (rTcCalr), the parasite responsible for Chagas’ disease, binds to Canine Transmissible Venereal Tumor (CTVT) cells from primary cultures and to a canine mammary carcinoma cell line. A Complement-binding assay indicated that interaction of the first component C1q with these tumor cells operated independently of the rTcCalr-presence. This apparent independence could be explained by the important structural similarities that exist among rTcCarl, endogenous normal canine and/or mutated calreticulins present in several types of cancer. In phagocytosis assays, tumor cells treated with rTcCalr were readily engulfed by macrophages and, co-cultured with DCs, accelerated their maturation. In addition, DCs maturation, induced by tumor cells co-cultured with rTcCalr, activated T cells more efficiently than DCs, treated or not with LPS. In an apparent paradox, a decrease in MHC Class I expression was observed when these tumor cells were co-cultivated with rTcCalr. This decrease may be related to a down regulation signaling promoting the rescue of MHC I. Possibly, these in vitro assays may be valid correlates of in vivo sceneries. Based on these results, we propose that rTcCalr improves in vitro the immunogenicity of two widely different tumor cell lines, thus suggesting that the interesting properties of rTcCalr to boost immune responses warrant future studies.     

雪峰虫草对DC-CIK增殖及HepG-2细胞杀伤作用的实验研究

目的:研究雪峰虫草对DC-CIK细胞增殖及肝癌Hep G-2细胞杀伤作用。方法:常规分离健康人外周血单个核细胞并诱导生成DC细胞和CIK细胞,将DC细胞与CIK细胞按1∶5共培养7 d后给药组加入不同浓度的雪峰虫草水提取物,第10天观察形态并计数各组DC-CIK细胞;收集培养第10天的DC-CIK细胞作为效应细胞,对数生长期Hep G-2肝癌细胞作为靶细胞,使Hep G-2∶DC-CIK靶效比为1∶5,cck-8法检测DC-CIK对Hep G-2的杀伤率。结果:雪峰虫草水提物组对DC-CIK有显著的促增长作用,其作用的最佳浓度为0.1 mg/ml。雪峰虫草诱导的DC-CIK细胞对肝癌Hep G-2细胞的杀伤作用优于常规方法培养的DC-CIK细胞;常规方法培养的DC-CIK细胞加雪峰虫草与常规方法培养的DC-CIK细胞对肝癌Hep G-2细胞的杀伤作用无显著性差异,雪峰虫草体外直接杀伤肝癌Hep G-2细胞的作用不明显。结论:雪峰虫草通过促进DC-CIK细胞增殖而增强其杀伤肝癌Hep G-2细胞的作用。     

Multipotent stem and progenitor cells of the olfactory epithelium

In recent decades, a wide spectrum of fetal and embryonic stem and progenitor cells were used for cell therapy of diseases of the central nervous system, but the olfactory glial ensheathing cells exhibited certain advantages due to their biological properties and capacity to stimulate regeneratory processes in spinal injury. The therapeutic effect of a heterogeneous complex of olfactory epithelial cells is more pronounced; apart from glial ensheathing cells, this complex includes fibroblasts, Schwann cells, stem and progenitor cells of this structure. The use of minimally invasive methods for isolation of human olfactory epithelial tissue is important for clinical practice, because they provide cells for autologous transplantation and rule out graft rejection immune reaction and the risk of transmission viral infection and transfer of genetic defects, which can be associated with allotransplantation. __________ Translated from Kletochnye Tekhnologii v Biologii i Medicine, No. 4, pp. 185–193, December, 2006     

A Cross‐Talk of Decidual Stromal Cells,Trophoblast, and Immune Cells: A Prerequisite for the Success of Pregnancy

Embryo implantation and formation of a functional placenta are complex processes that require a plethora of regulatory mechanisms involving both mother and embryo cells. Recently, an important role in this complicated cells and factors network was assigned to the decidual stromal cells (DSC) and trophoblast cells. Decidualization includes biochemical changes that trigger DSC to produce a number of factors required for the implantation and induction of immunotolerance in maternal immune system. Immunotolerance is achieved by a cascade of strictly controlled events starting with selective homing of immune cells to the feto‐maternal site, regulated proliferation, and predominant differentiation into a regulatory type of immune cells. Furthermore, cytotoxic effector functions are reduced owing to the influence of steroid hormones, factors, cytokines, and inhibitory receptors. Altogether the entire immune system of the mother is switched to tolerogenic functional state which is a prerequisite for the successful maintenance of pregnancy.     

胚胎干细胞诱导发育为树突状细胞的研究

目的：探讨胚胎干细胞（ESC）诱导分化为树突状细胞（DC）的实验方法，实现体外大规模扩增高纯度DC用于临床免疫治疗。方法：E14小鼠胚胎干细胞系在GM-CSF与IL-3联合作用下经胚胎体（EB）诱导分化为DC。不成熟DC （im-DC）流式细胞仪检测CD11c、CD80、CD86、MHC II-DR表达。用磷酸脂多糖（LPS）促进DC的成熟，收获细胞后观察细胞形态及摄片并做扫描电镜检查，分析细胞表型并与不成熟DC细胞表型做对比，异体淋巴细胞增殖实验行功能检测。结果：ES细胞来源DC呈典型DC形态学表现。im-DC CD11c、CD80、CD86、MHC-II表达低,m-DC CD11c、CD80、CD86、MHC-II的表达均较前明显升高。功能检测发现，ES细胞来源的DC具有强烈的激发同种异体淋巴细胞增殖的作用，证实ES细胞来源的DC具备正常的免疫学功能。结论：使用GM-CSF联合IL-3能成功诱导E14胚胎干细胞发育为DC。故ES细胞可作为DC来源的一条新途径，对于体外大规模制备DC用于免疫过继治疗提供了一个较好的方法。     

含噻唑烷-4-酮的糖类衍生小分子免疫调节剂对人淋巴细胞分化的影响

目的 研究含噻唑烷-4-酮的糖类衍生小分子免疫调节剂对人外周血淋巴细胞活化与分化的影响.方法 从健康成年人分离外周血单个核淋巴细胞,经ConA+免疫调节剂CH1a、CH2a、CH1b CH2b和匹多莫德(pidotimod)刺激48 h后,收集培养上清,ELISA法检测IL-2、IL-4和IFN-γ含量；72 h后MTT法检测细胞增殖率；经ConA+免疫调节剂CH1a、CH2a、CH1b CH2b和pidotimod刺激,孵育72 h后收获细胞,利用流式细胞技术检测细胞表面黏附分子.结果 所有样品均可促进T细胞增殖；免疫调节剂CH1a、CH2a和pidotimod上调CD3、CD4、CD19和CD16CD56的表达并促进IL-2和IFN-γ分泌.免疫调节剂CH1b、CH2b上调CD3、CD4、CD19和CD16CD56的表达并促进IL-2和IL-4分泌.结论 免疫调节剂CH1a、CH2a和pidotimod有可能诱导Th0向Th1分化并可提高B细胞和NK细胞增殖活化水平.而CH1b、CH2b则有可能诱导Th0向Th2分化并提高B细胞和NK细胞的增殖活化水平.     

Effect of hypophysectomy on endocrine cell types in rat gastrointestinal mucosa

The effect of hypophysectomy on the gastrointestinal tract was studied in the rat 8 wk after operation, particularly regarding the frequency and distribution of serotonin, somatostatin and gastrin-immunoreactive cells. Body weight, the length of the intestine and the thickness of the mucosa of the antrum and small intestine were all reduced in the hypophysectomised rats compared with sham-operated and untreated controls. In the hypophysectomised animals the serotonin-immunoreactive cells were fewer in the antrum and caecum, whereas they were more numerous in the proximal large intestine. There were fewer gastrin-immunoreactive cells in the antrum, while the somatostatin-immunoreactive cells were more numerous in the antrum and caecum. The significant influence of hypophysectomy on the gastrointestinal tract could be direct, but could also be associated with the marked effect of pituitary deficiency on endocrine cells, known to exert both trophic and antitrophic actions. However, it could also be an indirect effect on metabolism, resulting in lower food intake, other endocrine cell systems, and growth factors.     

Origin and differentiation of dendritic cells

Despite extensive, recent research on the development of dendritic cells (DCs), their origin is a controversial issue in immunology, with important implications regarding their use in cancer immunotherapy. Although, under defined experimental conditions, DCs can be generated from myeloid or lymphoid precursors, the differentiation pathways that generate DCs in vivo remain unknown largely. Indeed, experimental results suggest that the in vivo differentiation of a particular DC subpopulation could be unrelated to its possible experimental generation. Nevertheless, the analysis of DC differentiation by in vivo and in vitro experimental systems could provide important insights into the control of the physiological development of DCs and constitutes the basis of a model of common DC differentiation that we propose.     

Adhesion of Candida tropicalis to polystyrene and epithelial cell lines: Insights of correlation of the extent of adherent yeast cells among distinct surfaces

Candida tropicalis is an emerging fungal pathogen associated with high mortality. We aimed to compare adherence capability of C. tropicalis to polystyrene and epithelial cell lines (HeLa and Vero), and determine whether adherent blastoconidia is cell-type specific. Blastoconidia adhesion to epithelial cells and polystyrene were determined by crystal violet assay. The percentage of epithelial cells with adhered blastoconidia and the number of adhered blastoconidia per cell line were determined by light microscopy. The correlation between adhesion surfaces was assessed by Pearson's correlation coefficient. The adhesiveness of C. tropicalis to polystyrene was greater than that observed for ephitelial cells. High correlation values (r² 0.9999222, p 0.007941) were found for the adhesion capability between biotic and polystyrene surface for isolates 100.10 (obtained from blood) and 335.07 (obtained from tracheal secretion). The number of adherent blastoconidia per HeLa cell was greater in comparison to that observed for Vero cells (P < 0.05). Further, high correlation (r² 1, p 0.0001) was found for the adhesion ability between HeLa cells and Vero cells. The results suggest a correlation of C. tropicalis adhesion capability among different surfaces, and that the adhesion to epithelial cells is specific to the cell type.     

一种基于海马位置细胞选择机制的空间认知模型

生物学研究表明,位置细胞是大鼠知晓当前所处空间位置的主要依据。由于网格细胞是位置细胞的主要信息输入源,因此需要构建由网格细胞到位置细胞的映射模型。针对这一问题,本文提出一种网格细胞到位置细胞的逆传播误差神经网络映射模型,实现在给定区域内对位置的精确表达。又依据边界细胞对环境边界特异性放电这一生理特性,实现利用边界细胞对网格野位相的周期性重置,使该模型完成任意大小空间中的位置认知。本文设计了仿真实验对比理论位置细胞板的活动情况,又分别对比竞争型神经网络模型的耗时和RatSLAM位姿细胞板的定位误差。实验结果表明,本文模型能够得到单一的位置野,并在耗时实验中较竞争型神经网络模型算法效率提高85.94%;在定位实验中较RatSLAM位姿细胞板的平均定位误差下降41.35%。因此本文提出的位置认知模型不仅可以实现网格细胞到位置细胞之间信息的高效传递,而且能够在任意大小的空间区域内实现自身位置的精确定位。     

Fine-needle aspiration biopsy of pilomatrixoma: Still a diagnostic trap for the unwary

Of the 16 cases of fine-needle aspiration biopsy (FNAB) of pilomatrixomas reported since 1982, only 25% were correctly diagnosed prior to excision. The most common pitfall encountered was a false-positive or suspicious diagnosis of a carcinoma. All the reported cases had a polymorphous cellular and noncellular composition on low-power examination, including numerous basaloid cells, ghost cells, squamoid cells, foreign body giant cells, mixed inflammatory cells, keratin clumps, and granular debris which might be easily mistaken for a malignant necrotic background. Amongst these, ghost cells were the critical pathognomonic feature. This paper reported a further finding that had been under-emphasized in the literature: masses of refractile orangeophilic keratin clumps representing compact sheets and stacks of ghost cells. Their presence should alert the observer to search for the more diagnostic dispersed forms which otherwise might be inconspicuous and easily overlooked. © 1994 Wiley-Liss, Inc.