Urszula SKALSKA, Ewa KONTNY

Rregenerative and Immunomodulatory Properties of Adipose-Derived Mesenchymal Stem Cells

Summary: Many studies on medical application of adipose-derived mesenchymal stem cells are currently performed. Regenerative and immunomodulatory properties of these cells are very promising. In this paper we review the literature concerning differentiation potential of adipose-derived stem cells and their effects on immune response. We demonstrate the clinical application of these cells and, shortly, their phenotype and isolation methods. 

Key words:
  adipose-derived mesenchymal stem cells, regeneration, differentiation, immunomodulation, adipose tissue, medical application
[Postępy Biologii Komórki 2011; 38: 363–378]

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Katarzyna ROSZEK, Joanna CZARNECKA, Michał KOMOSZYŃSKI

Ependyma and Subependyma of Adult Mammalian Brain as a Source of Neural Stem Cells

Summary:  The brain of adult animals, including humans, sustained the ability to create new glial cells and neurons. This process is called postnatal neurogenesis. It is possible owing to the presence of neuronal stem cells in the neurogenic zones. The subependymal layer, a part of periventricular zone, demonstrates the highest intensity of neurogenesis. Ependymal cells, forming the external lining of the lateral ventricles, can also effectively differentiate into cells of the nervous system. Ependymal cells (ependymocytes) originate from radial glia and are created during embrional and early postnatal development. Ependymocytes of adult mammalian brain form migrating cells differentiating into astrocytes and neurones. Ependymal cells express neuroprogenitor markers like Sox2 or nestin and adult stem cells marker – CD133. Subependyma is layered below the uniform ependyma lining. It is formed of a few diverse types of cells. There are numerous data indicating that subependymal, GFAP-positive astrocytes proliferate intensively and they have the characteristics of neural stem cells. The subependymal zone is a niche for neural stem cells, neuronal and glial precursor (progenitor) cells, neuroblasts and glioblasts that are immature neurons and glia, respectively. Ependymal and subependymal zone emerges to be a rich source of neural stem cells. Neural stem cells (NSCs) are primary cells with the ability of self-renewal or differentiation into one of three types of nervous system cells: neurons, oligodendrocytes or astrocytes. NSCs isolated from neurogenic zones of adult mammalian brain can be cultured in vitro in two systems: as monolayer system or as culture of neurospheres. Neurospheres cultured in vitro are spherical or elipsoidal structures formed of hundreds of cells surrounded by an envelope rich in extracellular matrix components. The cells forming neurosphere differ in their size, presence of cytosolic granules, number of mitochondria, the phase of cell cycle. Neurospheres appear as complex biological structures in which events such as phagocytosis, mitosis, apoptosis and even necrosis occur at the same time. The amount of NSCs in neurospheres is estimated as about 0.16%. In physiological conditions proliferation and differentiation of neural stem cells are precisely regulated through different interactions and signalization systems within the niche. The attempt to recognize these complex interactions and to fully characterize all the factors and signaling systems is still a challenge for the researchers. In this article we describe only these molecules and pathways of signalization that are quite well characterized. Our understanding of the mechanisms regulating proliferation and differentiation of NSCs will allow to precisely control these processes in in vitro cultures. These findings will help to applicate NSCs in the therapy of neurodegenerative diseases like Alzheimer or Parkinson disease, brain injury and stroke.

Key words:  ependyma, subependyma, neural stem cells, neurospheres, differentiation control

[Postępy Biologii Komórki 2011; 38: 3791–393]

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Maciej KWIATEK, Anna KWAŚNIEWSKA

Role of Regulatory T Cells in Pregnancy

Summary: During gestation, CD4+/CD25+ regulatory T  cells (TREG) play crucial role in mechanisms by which maternal immunological system tolerates semiallogeneic fetus. Paternal antigens as well as maternal hormons contribute to the pregnancy- associated increase of  TREG population. TREG regulate immunological response by cell-cell contact and indirectly by cytokines. TREG population expands during human pregnancy, that may be detected both in peripheral blood and in decidua. At the fetal-maternal interface TREG create tolerant microenviroment by interaction with other immune cells and by inducing the expression of immune regulatory molecules such as TGF-b, LIF or HO-1. The importance of TREG for a normal pregnancy was proven  by many studies. Diminished numbers of  CD4+/CD25+ regulatory T cells or their improper function is associated with implantation failure, fetal rejection, miscarriage and pre-eclampsia.

Key words: 
CD4+/CD25+ regulatory T cells, pregnancy
[Postępy Biologii Komórki 2011; 38: 395–406]

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Agnieszka CHYRA, Katarzyna GAWEŁ, Joanna CICHY

Chemerin – a New Regulator of Metabolic and Immune Processes

Summary: Chemerin is recently discovered ligand for a chemokine receptor like-1 (CMKLR1) expressed primarily by plasmacytoid dendritic cells, macrophages and NK cells. Chemerin is mainly synthesized by the liver and circulates in the blood in an inactive precursor form – prochemerin. At the site of inflammation prochemerin undergoes proteolytic activation that unleashes its chemotactic activity for CMKLR1+ cells. As a chemotactic factor for a specific subsets of  leukocytes, chemerin contributes to the pathogenesis of chronic inflammatory diseases such as psoriasis, lupus erythematosus and lichen planus. Recent data have demonstrated that chemerin is not only a chemotactic protein for immune cells but also plays a role in regulating differentiation, insulin-induced glucose uptake and lipolysis in adipocytes probably via an autocrine manner. Being a chemoattractant and an adipokine (signaling molecule secreted by adipose tissue), chemerin is a potential factor involved in the pathogenesis of  metabolic disorders characterized by a chronic, low-grade inflammation and macrophage infiltration. This is supported by circulating chemerin levels that differ significantly  between obese and diabetic patients compared with healthy individuals. Serum chemerin levels are also correlated with metabolic syndrom-related parameters including BMI, triglycerides and hypertension. In this review we summarize current knowledge about chemerin with focus on  the role of this protein in regulating immune responses and metabolic processes.

Key words: chemerin, CMKLR1, chemoattractant, adipokine
[Postępy Biologii Komórki 2011; 38: 407–421]

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Ewelina ROGALA, Aldona NOWICKA, Iwona WERTEL, Grzegorz POLAK, Rafał TARKOWSKI, Józef KOTARSKI, Jan KOTARSKI

Th17 Lymphocytes a New Ally in the Fight Against Ovarian Cancer?

Summary: Th17 are a newly discovered population of T helper lymphocytes characterized by the production of IL-17 (IL-17A). Interleukin 17 activates production of cytokines which are responsible for migration of neutrophils and development of inflammatory reaction. Among the other cytokines secreted by Th17 cells are TNF-a, IL-1b, IL-6 and IL-22. Development of Th17 lymphocytes gave rise numerous researches on mechanisms leading to differentiation of CD4+ cells towards new subpopulation and enabled to define factors conditioning the line. Murine Th17 lymphocytes differentiate in a specific cytokine environment which include TGF-b, IL-6 and  IL-21, whereas human Th17 cell development requires TGF-b, IL-1b, IL-2 in combination with IL-6, IL-21, or IL-23. Th17 lymphocytes are currently the subject of intensive examinations concerning their role in the pathogenesis of many autoimmune, inflammatory and allergic diseases. More and more attention is directed into their role in anti-tumor immunity. Although the presence of Th17 lymphocytes in the ovarian cancer microenvironment has been proven, their influence on the proliferation of cancer cells is still not defined. Controversies around the role of Th17 in the pathogenesis of different kinds of tumor indicate that IL-17 functions either anti-tumor or, on the contrary, conduce the development of the tumor. Proinflammatory and angiogenesis are important  mechanisms conditioning the proliferation of the tumor, in which the lymphocytes play the crucial role. Simultaneously, a lot of data indicate that increased expression of IL-17 can be in favour of anti-tumor function of Th17 lymphocytes. Profound cognition of  the biology of Th17 lymphocytes, their differentiation and supression mechanisms require further reasearches, results of which enable to elaborate on new methods of anti-tumor therapy.

Key words: Th17 lymphocytes, interleukin 17, ovarian cancer, anti-tumor response

[Postępy Biologii Komórki 2011; 38: 423–433]

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Barbara ŻYŻYŃSKA-GRANICA

Interleukin 15 – What Do We Know? THE Structure, Receptors And Inhibitors

Summary: Interleukin 15 (IL-15) is a pleiotropic cytokine with a wide spectrum of activity. The significant role of  IL-15 in the pathogenesis of inflammatory and autoimmune processes, infectious diseases and cancer suggests a possibility of a therapeutic intervention by blocking the biological activity of this cytokine. The methods of blocking IL-15, which have been already developed, are based either on the administration  of anti-IL-15 and anti-IL-15 receptor antibodies or on the modifications leading to a soluble receptor molecule or a mutated IL-15, exhibiting properties of competitive antagonists. There are also other compounds used, which do not interact directly with elements of the complex of IL-15 and its receptor. Nevertheless, none of these strategies have been introduced into a wide clinical use. New perspectives for the research on the selective and efficient inhibition of IL-15 has been created by a recent definition  of  IL-15 and its receptor complex structure. The article discusses the structure of IL-15 and its receptor, their interactions and reviews the major advances in the research on the inhibition of IL-15.

Key words:
 cytokine; interleukin 15; interleukin 15 receptor ??subunit; antagonist; antibody.
[Postępy Biologii Komórki 2011; 38: 435452]

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Patrycja WIZIŃSKA, Piotr DZIĘGIEL

Laser Microdissection – High-Tech Technique Applied in Molecular Biology

Summary: Molecular analysis are mostly carried out in heterogeneous biological material, and results obtained in this way illustrate the status quo that existed in different cell types, also in cells that are not the object of our interest. This article aims to familiarize the reader with a technique for precisely obtaining material for molecular studies, which is laser microdissection. This method allows the separation of even a single cell from a heterogeneous material almost unchanged, both morphologically and biochemically. This publication is a summary of knowledge about the types of laser microdissection, the general principles of their operation and examples of their applications.

Keywords:   laser microdissection, molecular biology

[Postępy Biologii Komórki 2011; 38: 453–465]

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Ewa KACPRZYŃSKA, Izabela MACIEJEWSKA

Dental Pulp Stem Cells. Possibilities of Application in Contemporary Dentistry And Future Directions – Review

Summary: Introduction: multipotential stem cells are already applied for guided tissue regeneration, therefore the challenge of contemporary dentistry is to apply dental pulp stem cells for guided dentin regeneration. The in vitro and in vivo studies as well as a molecular analysis showed such a possibility. So far, bone marrow stem cells (BMSC) have been successfully utilized for treatment of the autoimmuno-logical syndromes and cancers. BMSC have been well recognized, however the way of their isolation may be hazardous for a patient. Thus researchers are taking efforts to recruit stem cells from the better accessible sources. Molecular studies discovered the presence of multipotential stem cells in dental pulp (DPSC). When culture under the scrutinized conditions the dental pulp stem cells differentiate into odontoblasts and subsequently in vivo produce a dentin and dentin - pulp complex. It is expected that tissue engineering with DPSC will allow for replacement of traditional dental materials to in vitro generated dentin. Aim of the study: a review of the newest data concerning specificity of DPSC, as well as their possibilities of application in dentistry has been made. Moreover comparison of DPSC and BMSC has been studied.

Key words: stem cells, guided tissue regeneration, odontoblasts
[Postępy Biologii Komórki 2011; 38: 467–473]

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Krystyna FILIPIAK, Agnieszka MALIŃSKA, Michał NOWICKI, Dariusz KRUPA, Maciej ZABEL 

Innovative  Methods of Archiving, Presentation and Providing Access to Histological Sections at the Example of the Center of Morphologic Images Archivization and Digital Database of Microscopic Pictures Operating in Poznan University of Medical Sciences

Summary: The dynamic development of technical sciences and information technology allows now for acquisition of microscopic images of histological sections, not only using digital cameras, but also through specialized devices called scanners. The images obtained using scanners and stored in a computer storage device are called virtual slides and, together with special software, are known as virtual microscopy. The virtual slides can be analyzed on a computer monitor by panoramic viewing or using a detailed image examination at higher magnification. In many  research and education institutions in both the US and Europe, the virtual microscopy is used for teaching and training purposes. In the academic year of 2009/2010, Department of  Histology and Embryology, University of  Medical Sciences in Poznań, as one of the first in Poland, has created a virtual database for educational purposes. This database has resulted from archiving the traditional images of histological slides in the form of digital images. So far, more than 130 virtual slides have been acquired and catalogued in 24 thematic folders, available for medical students participating in histology, embryology and cell biology courses. Telepathology is the second branch which use virtual microscopy. Virtual microscope allows to discuss and resolve medical/diagnostic problems with the use of telecommunication systems and information technology. The existing internet platforms offer access to virtual microscopes and virtual slides. In June, 2011 the Center of Morphologic Images Archivization and Digital Database of Microscopic Pictures in the Department of Histology and Embryology, Poznan University of Medical Sciences launch an online platform (www.caom.pl), aimed at providing a central database of scanned histological sections with images of physiological tissues, and pathological, rare and unusual lesions, including tumors.

Key words:  virtual microscopy, virtual slide, telepathology
[Postępy Biologii Komórki 2011; 38: 475–489]

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Adam MOL, Magdalena STOLAREK  

Induced Damages of DNA by Mutagens and Mechanisms of Their Formation

Summary: The genomes of all living organisms are extremely stable. DNA in the cell is replicated during cell division and passes all the genetic information to the next generation. It is essential for all living organisms to ensure proper functioning and propagation of their genetic information. Due to constant exposure of the genome to various endogenous and exogenous agents, however, the DNA becomes damaged leading to a large variety of DNA lesions. The endogenously generated damage of DNA is known as spontaneous DNA damage, which is produced by reactive metabolites and defects in normal processes of DNA replication or recombination. The exogenous DNA-damaging agents include chemical mutagens, for example base analogs, alkylating agents and aromatic compounds, and physical mutagens: UV light, ionizing radiation and high temperature. The DNA lesions produced by these damaging agents could result in a base modification, such as alkylation and oxidation, base deletion, cyclobutane dimers, 6–4 photo-products, strand breaks, intra- and interstrand cross-links. Those damages of DNA have genotoxic or cytotoxic impact to the cell. Although most mutations are either neutral or harmful, some mutations have a positive effect on an organism. In this case, the mutation may enable the mutant organism to withstand particular environmental stresses better than wild-type organisms, or to reproduce more quickly. Mutagenesis is used to induce mutations at high frequency that include ionizing radiation and chemical mutagens for basic plant research and plant breeding.

Key words: DNA damage, chemical mutagens, physical mutagens, induced mutations, mutagenesis
[Postępy Biologii Komórki 2011; 38: 491–505]

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Łukasz RĄPAŁA, Rafał STARZYŃSKI, Piotr TRZECIAK, Anna Maria DUSZEWSKA

Structure and Function Oviduct-Specific Glycoprotein 1

Summary: Oviduct specific glycoprotein 1 (OVGP1) also known as pOSP, MUC-9, sOP92, EAP, EGP and OGP, is produced by non-ciliated oviductal epithelium in many mammalian species. After its secretion to the oviductal fluid OVGP1 participates in the final gamete maturation, sperm capacitation, fertilization and supports early embryonic development. Secretion and expression of OVGP1 is regulated by steroid hormones and depends on the oestrus cycle.  Molecular analysis of OVGP1 indicated that it is highly conserved at both amino acid and nucleotide levels. The main divergence has been observed in the carboxy terminal region containing deletions, insertions and tandem-repeat sequences containing O- and N- glycosylation sites. The carbohydrates protect OVGP1 protein and modulate its specificity and biological activity. Additionally,  other post-translational modifications (phosphorylation, sialic acid residues, sulphation) contribute to the diversity of actions of OVGP1 among different species.

Key words: OVGP1, OGP, MUC 9, oocyte, spermatozoa, embryo
[Postępy Biologii Komórki 2011; 38: 507–516]

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Katarzyna KABAŁA

Structure and Regulation of Plant Vacuolar H+-ATPase

Summary: lant vacuolar H+-transporting ATPases (V-ATPases) are ATP-driven proton pumps, located mainly in the vacuolar membrane, that generate proton motive force used to energize secondary active transports operating at the tonoplast. V-ATPases are the oldest and most complicated proton pumps found in plant cells. Enzyme subunits are divided into two major domains, the catalytic peripheral V1 domain responsible for ATP hydrolysis and the membrane-integral V0 domain responsible for H+ translocation. V1 sector consists of eight subunits named A-H whereas V0 complex is composed of a, c, c”, d, and e subunits. In Arabidopsis thaliana, the 13 V-ATPase subunits are encoded by a total of 28 VHA genes suggesting the presence of individual subunit isoforms and different V-ATPase complexes specific to plant organs, tissues or physiological and developmental stages. The activity of plant V-ATPases is subjected to regulation at both the transcriptional and posttranslational levels. Potential mechanisms of biochemical regulation include reversible phosphorylation, redox regulation and modification induced by changes in the lipid composition of membrane. It has been postulated that under environmental stress the V-ATPase functions as a stress response enzyme, undergoing moderate changes in expression of subunits and modulation of enzyme activity. Since it was involved in ecophysiological adaptations at the molecular level, the V-ATPase was denominated an „eco-enzyme”. Numerous studies have confirmed an essential role of the V-ATPase in plant tolerance to environmental stresses including salinity, heavy metals and low temperature.

Key words: stem cells, guided tissue regeneration, odontoblasts
[Postępy Biologii Komórki 2011; 38: 517–532]

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Ewa KACPRZYŃSKA, Izabela MACIEJEWSKA

Alanine Aminotransferase in Higher Plants

Summary: Alanine:2-oxoglutarate aminotransferase (EC 2.6.1.2), also called alanine aminotransferase (AlaAT), catalyses transamination reaction between L-alanine and 2-oxoglutarate and the reverse reaction between L-glutamate and pyruvate. It is one of the most important enzymes involved in the synthesis and degradation of L-alanine. There are multiple isoenzymes of this enzyme (2 to 6) present in plants. Subcellular location of these isoenzymes appears to be directly associated with their metabolic role: (i) in C4 plants (Paniculum miliaceum) alanine aminotransferase participates in the transfer of C3 units (pyruvate)  from  mesophyl  to  bundle  sheath cells,   (ii)  peroxysomal  alanine  aminotransferase   exhibiting   L-glutamate : glyoxylate aminotransferase activity is involved in regulation of photorespiration, (iii) alanine aminotransferase lacking  L-glutamate : glyoxylate aminotransferase activity participates in hypersensitivity response to virus attack and (iv) regulates the alternative oxidase activity in miotchondria. Activation of alanine aminotransferase and simultaneous L-alanine acumulation was observed in plants subjected to hypoxia. On this base it was proposed, that this enzyme is involved in the response mechanisms that allow plants to survive under various adverse conditions such as periodic flooding of fields or lingering of snow cover. Research on transgenic plants also indicated its crutial role in nitrogen metabolism. Moreover peroxysomal alanin aminotransferase capable of using glyoxylate as amino group acceptor appeared to be involved in regulation of serine, citruline and glycine contents in leaves.

Key words: alanine aminotransferase, isoenzymes, hypoxia, nitrogen deprivation, photorespiration
[Postępy Biologii Komórki 2011; 38: 533–544]

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