Bogusław Machaliński
Publications
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2.53Impact points
Activation of phospholipase A(2) by low levels of fluoride in THP1 macrophages via altered Ca(2+) and cAMP concentration.
Prostaglandins, leukotrienes, and essential fatty acids. 02/2012; 86(3):99-105.
Phospholipases (PLA's) participate in the regulation of physiological and pathological processes in the cell, including the release of pro-inflammatory mediators and stimulation of inflammatory processes. It is also well known that fluoride can increase the inflammatory reactions. Therefore we d... [more] Phospholipases (PLA's) participate in the regulation of physiological and pathological processes in the cell, including the release of pro-inflammatory mediators and stimulation of inflammatory processes. It is also well known that fluoride can increase the inflammatory reactions. Therefore we decided to examine the effect of fluorides in concentrations determined in human serum on cPLA(2) and sPLA(2) activity. The incubation of macrophages in fluoride solutions significantly increased the amount of synthesized cellular cAMP, intracellular calcium and sPLA(2) activity in a dose-dependent pattern. The cPLA(2) activity, estimated by the amount of released arachidonic acid, increased significantly when 10μM NaF was used. The results of our study suggest that fluoride may change the activity of phospholipases in macrophage cells. Probably, increased cAMP concentration activates protein kinase C (PKC) and thus stimulates PLA(2). cAMP also regulates the passage of Ca(2+) through ion channels, which additionally influence PLA(2) throughout Ca(2+)-calmodulin dependent protein kinase.
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3.50Impact points
Bone marrow of multiorgan donors underutilized: implications for improvement of accessibility of hematopoietic cells for transplantations.
Transplantation. 12/2011; 93(2):165-71.
The demand for human hematopoietic stem and progenitor cells (HSPCs) for transplantation is increasing. Thus, effective alternative sources of HSPCs are required. Consequently, we sought to expand the accessibility of hematopoietic cells for clinical purposes by the investigation of hematopoietic re... [more] The demand for human hematopoietic stem and progenitor cells (HSPCs) for transplantation is increasing. Thus, effective alternative sources of HSPCs are required. Consequently, we sought to expand the accessibility of hematopoietic cells for clinical purposes by the investigation of hematopoietic reconstitution after transplantation of human HSPCs harvested from the bone marrow (BM) of heparinized deceased organ donors (HDODs). For multipart research comparison, human BM HDODs-, healthy donor-derived, umbilical cord blood nuclear cells, or CD34(+) cells were transplanted into sublethally irradiated NOD/SCID mice. Twenty-eight days after transplantation nuclear cells were isolated from the murine BM, spleen, and peripheral blood and were used to quantitatively detect human CD45 antigen by quantitative real-time reverse transcriptase-polymerase chain reaction and flow cytometry. The clonogenic growth of human colony-forming units was also investigated. We found that umbilical cord blood-derived HSPCs showed the greatest transplantation potential in our in vivo model. Interestingly, the transplantation potential of HSPCs collected from the BM of HDODs was of the same quality as cells obtained from healthy BM donors. Based on these results, we conclude that HDODs are a strongly underappreciated source of HSPCs that are ready to use for clinical purposes.
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2.44Impact points
Complement system activation and endothelial dysfunction in patients with age-related macular degeneration (AMD): possible relationship between AMD and atherosclerosis.
Acta ophthalmologica. 11/2011;
Age-related macular degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). First, an association between AS and AMD is apparent from the analyses of the histological and biochemical structure of atherosclerotic plaques in the vascular wall... [more] Age-related macular degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). First, an association between AS and AMD is apparent from the analyses of the histological and biochemical structure of atherosclerotic plaques in the vascular walls and retinal drusen, the hallmark of AMD. Second, there is considerable evidence implicating endothelial dysfunction in the pathogenesis of both disorders, and cellular oxidative stress appears to be a common denominator underlying this process. Moreover, there are observations that the complement system (CS) triggering inflammatory response contributes to the onset and advancement of both diseases. The CS plays a role in the generation of drusen and neovascularization in AMD as well as in vascular endothelium activation, cell damage and ultimately atherosclerotic plaque formation in the course of systemic arteriosclerosis. It is widely recognized that both AMD and AS are not only related to local stimulation of the CS, but also result in its systemic activation. In addition, a specific Y402H polymorphism of the complement inhibitor factor H has been found to be associated with the incidence of both AMD and AS. Here, we propose a linking hypothesis between CS activation, endothelial dysfunction and the pathogenesis of two common and age-related pathological processes, AS and AMD. We also discuss the potential therapeutic value of pharmacological modulation of CS activation in these disorders.
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2.44Impact points
Different strategies of mixed chimerism induction may determine stem/progenitor cell populations in recipient mice.
Transplant immunology. 09/2011; 26(1):34-41.
Mixed chimerism has been suggested to induce tolerance to transplanted alloantigens. As the precise influence of mixed chimerism induction on the host organism has still not been fully elucidated, the aim of the present study was to explore this phenomenon in relation to the stem cell compartment. T... [more] Mixed chimerism has been suggested to induce tolerance to transplanted alloantigens. As the precise influence of mixed chimerism induction on the host organism has still not been fully elucidated, the aim of the present study was to explore this phenomenon in relation to the stem cell compartment. The experiment was performed on B6.SJL-Ptprc(a)Pep3(b) mice. Mixed chimerism induction protocols involved 3 Gy TBI (Day -1 of the experiment), injection of 20-30 × 10(6) Balb C bone marrow cells (Day 0), and administration of blocking antibodies against CD40L (Day 0 and Day 4), anti-CD8 (Day -2) with/without anti-NK1.1 (Day -3). Selected groups of mice were also treated with cyclophosphamid (175 mg/kg) on Day 2. The presence of mixed chimerism was assessed in peripheral blood, bone marrow, and spleen, as well as in various subpopulations of leukocytes (CD4(+), CD8(+), CD45/B220(+), Gr-1(+), lin(-)/Sca-1(+)/c-kit(-), lin(-)/Sca-1(+)/c-kit(+), lin(-)/Sca-1(-)/c-kit(+)). Furthermore, the percentage of stem/progenitor cells (lin(-)/Sca-1(+)/c-kit(-), lin(-)/Sca-1(+)/c-kit(+), lin(-)/Sca-1(-)/c-kit(+), VSEL, HSC) was analysed for the first time in bone marrow and peripheral blood of chimeric mice. The range of mixed chimerism differed significantly among various cell populations: it was lowest in CD8-positive cells and lin(-)/Sca-1(+)/c-kit(-) cells, and highest in granulocytes. The induction of mixed chimerism revealed a significant impact on the stem/progenitor cell frequency in recipient mice, providing potential therapeutic insights into the long-term immunologic tolerance observed in chimeric mice. Collectively, these findings contribute to further optimization of mixed chimerism induction protocols and might help in the introduction of this phenomenon into clinical practice.
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2.10Impact points
Neural stem/progenitor cells circulating in peripheral blood of patients with neovascular form of AMD: a novel view on pathophysiology.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie. 08/2011; 249(12):1785-94.
The neovascular form of age-related macular degeneration (AMD) manifested with choroidal neovascularization (CNV) is one of the leading causes of rapid and irreversible visual loss. Recent reports suggest that bone marrow-derived stem/progenitor cells (SPCs) play a crucial role in the development an... [more] The neovascular form of age-related macular degeneration (AMD) manifested with choroidal neovascularization (CNV) is one of the leading causes of rapid and irreversible visual loss. Recent reports suggest that bone marrow-derived stem/progenitor cells (SPCs) play a crucial role in the development and progression of the disease. The purpose of this study was to investigate whether or not undifferentiated non-haematopoietic stem cells, including those capable of differentiating into neural phenotypes, play a role in the pathological state of CNV formation. Peripheral blood samples were collected from 46 patients diagnosed with CNV and from 46 controls. The CXCR4(+)Lin(-)CD45(-) stem cells were counted and analysed by flow cytometry. Using qRT-PCR and immunocytofluorescence, the expression of early neural and glial cell markers (β-III-tubulin, nestin, and glial fibrillary acidic protein) in the sorted cells was analysed, and correlated with plasma concentrations of stromal cell-derived factor 1 (SDF-1) (enzyme-linked immunosorbent assay), which is a pivotal chemokine that regulates the trafficking of SPCs. We found that the number of circulating CXCR4(+)Lin(-)CD45(-) cells did not differ in patients with active CNV as compared to the controls. However, we noticed significant intracellular overexpression of β-III-tubulin in the cells derived from AMD patients. Moreover, we observed significantly lower SDF-1 plasma levels in neovascular AMD patients compared to healthy individuals. Our findings suggest that neural progenitor cells, together with low SDF-1 concentrations, may play a considerable role in the process of AMD progression. Further investigations aimed at the precise elucidation of these issues may help with the future development of effective prevention against, and the treatment of, this disease.
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1.51Impact points
Stem Cells are mobilized from the bone marrow into the peripheral circulation in response to retinal pigment epithelium damage--a pathophysiological attempt to induce endogenous regeneration.
Current eye research. 07/2011; 36(7):663-72.
Stem cell regeneration of damaged tissue has recently been reported in many different organs. Here, we investigated the mobilization of different stem/progenitor cell (SPC) populations into the peripheral blood (PB), their subsequent homing to the injured retina (IR) and contribution to its regenera... [more] Stem cell regeneration of damaged tissue has recently been reported in many different organs. Here, we investigated the mobilization of different stem/progenitor cell (SPC) populations into the peripheral blood (PB), their subsequent homing to the injured retina (IR) and contribution to its regeneration in a retinal pigment epithelium (RPE) damage model induced by sodium iodate (NaIO(3)). Mobilization of SPCs was evaluated by flow cytometry. SPCs distribution in IR was assessed using bone marrow (BM)-derived GFP(+)Lin(-) cells transplanted intravenously into NaIO(3)-treated C57Bl/6 mice. The quantity of the chemokine SDF-1 in PB and IR was measured by ELISA and qRT-PCR, respectively. Apoptosis (TUNEL assay), cell proliferation (PCNA analysis) as well as functional retinal activity (electroretinogram) were examined at several time points after NaIO(3) administration. Mobilization of SPCs along with the highest cell proliferation and massive apoptosis within IR were observed on the third day after NaIO(3) administration. Similarly, donor GFP(+)Lin(-) cells were detected in the retina as soon as day 4 after NaIO(3) injection. Plasma levels of SDF-1 did not differ significantly in mice exposed to NaIO(3) compared to healthy controls, however mRNA for SDF-1 was overexpressed locally in IR. Functional retinal recovery was not achieved. Our study provides evidence that BM SPCs egress into PB and home to the injured retina, but are not capable of restoring its function. These results indicate that if the range of retinal destruction is profound, endogenous regeneration is ineffective and may ultimately require adjuvant therapeutic transplantation of specific SPCs subpopulations.
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5.08Impact points
Stem Cells, Including a Population of Very Small Embryonic-Like Stem Cells, are Mobilized Into Peripheral Blood in Patients After Skin Burn Injury.
Stem cell reviews. 05/2011; 8(1):184-94.
Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), as well as very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue and organ injury (e.g., heart infarct or stroke). We seek to determine whether these cells are a... [more] Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), as well as very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue and organ injury (e.g., heart infarct or stroke). We seek to determine whether these cells are also mobilized into PB in patients with skin burn injuries. Forty-four (44) patients (33-57 years of age) with total body surface burn area of 30-60%, as well as 23 healthy control subjects, were recruited and PB samples were harvested during the first 24 hours, day +2, and day +5 after burn injury and compared to normal controls. The circulating human CD34(+)CD133(+) cells enriched for HSPCs, as well as small CXCR4(+)CD34(+)CD133(+) subsets of Lin(-)CD45(-) cells that correspond to the population of VSELs, were counted by FACS and evaluated by direct immunofluorescence staining for pluripotency markers (Oct-4, Nanog, and SSEA-4). In parallel, we also measured by ELISA the serum concentration of factors that regulate stem cell trafficking, such as SDF-1, VEGF, and HGF. Our data indicate that skin burn injury mobilizes cells expressing stem cell-associated markers, such as CD133, CD34, and CXCR4, into PB. More importantly, we found an increase in the number of circulating primitive, small Oct-4(+)Nanog(+)SSEA-4(+)CXCR4(+)lin(-)CD45(-) VSELs. All these changes were accompanied by increased serum concentrations of SDF-1 and VEGF. Further studies are needed to fully assess the role of mobilized stem cells in the healing process to see if they can contribute to skin regeneration. Skin burn injury triggers the mobilization of HSPCs and CXCR4(+) VSELs, while the significance and precise role of mobilized VSELs in skin repair requires further study.
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2.47Impact points
Comparative effects of conjugated linoleic acid (CLA) and linoleic acid (LA) on the oxidoreduction status in THP-1 macrophages.
Journal of agricultural and food chemistry. 03/2011; 59(8):4095-103.
The aim of this study was to investigate the effect of conjugated linoleic acids (CLAs) on macrophage reactive oxygen species synthesis and the activity and expression of antioxidant enzymes, catalase (Cat), glutathione peroxidase (GPx), and superoxide dismutase (SOD). The macrophages were obtained ... [more] The aim of this study was to investigate the effect of conjugated linoleic acids (CLAs) on macrophage reactive oxygen species synthesis and the activity and expression of antioxidant enzymes, catalase (Cat), glutathione peroxidase (GPx), and superoxide dismutase (SOD). The macrophages were obtained from the THP-1 monocytic cell line. Cells were incubated with the addition of cis-9,trans-11 CLA or trans-10,cis-12 CLA or linoleic acid. Reactive oxygen species (ROS) formation was estimated by flow cytometry. Enzymes activity was measured spectrophotometrically. The antioxidant enzyme mRNA expression was estimated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was based on nonparametric statistical tests [Friedman analysis of variation (ANOVA) and Wilcoxon signed-rank test]. cis-9,trans-11 CLA significantly increased the activity of Cat, while trans-10,cis-12 CLA notably influenced GPx activity. Both isomers significantly decreased mRNA expression for Cat. Only trans-10,cis-12 significantly influenced mRNA for SOD-2 expression. The CLAs activate processes of the ROS formation in macrophages. Adverse metabolic effects of each isomer action were observed.
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[The role of circulating endothelial progenitor cells in the progression of retinopathy of prematurity--a prospective study].
Klinika oczna. 01/2011; 113(7-9):223-7.
Retinopathy of prematurity (ROP) is the primary cause of visual impairment in preterm infants. There are available data confirming that circulating endothelial progenitor cells (EPCs) are involved in forming the growing network of blood vessels in the developing retina. In this study we sought to ex... [more] Retinopathy of prematurity (ROP) is the primary cause of visual impairment in preterm infants. There are available data confirming that circulating endothelial progenitor cells (EPCs) are involved in forming the growing network of blood vessels in the developing retina. In this study we sought to explore potential relationship between concentration of circulating bone marrow-derived EPCs and development of ROP in prospective study. The study groups consisted of 90 preterm (23-36 weeks of gestational age), and 52 full-term control infants. EPCs were analyzed in cord blood (CB) and subsequently in peripheral blood (PB) in second and sixth week since delivery. The incidence and stage of ROP was prospectively documented in the preterm infants. EPC concentration in CB was considerably higher in the preterm infants developing ROP. In the preterm infants a noticeable decrease in PB EPC concentration within six weeks of the follow up was found, whereas in full-term infants EPC concentration was maintained at invariable level. Of note, in the sixth week since delivery, EPC concentration in preterm infants with ROP was lower compared to preterm infants without ROP. Increase in CB EPC concentration in preterm infants, including those developing ROP, indicates that the circulating EPC cells contribute to the process of blood vessel formation, and their number in CB reflects the degree of prematurity. Impaired blood vessel formation within retina in the course of ROP may result from decrease in circulating EPC number observed at the sixth week since delivery.
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0.57Impact points
[Stem cells in cardiological clinical trials].
Kardiologia polska. 01/2011; 69(6):601-9.
Stem cell-based therapy is a novel therapeutic strategy introduced into cardiology, although there are not any established standards within the stem/progenitor cell type employed, their preparation, rout of administration as well as methods controlling the pathophysiological and clinical parameters ... [more] Stem cell-based therapy is a novel therapeutic strategy introduced into cardiology, although there are not any established standards within the stem/progenitor cell type employed, their preparation, rout of administration as well as methods controlling the pathophysiological and clinical parameters after the cell application. The aim of the present work was a complex meta-analysis of the clinical trials carried out in this field. Over 1000 patients with myocardial infarction as well as circulatory failure have been treated with stem cell-based therapy so far, but the obtained results are not concordant. Progress within cell biology and biotechnology give hopes for development of more effective therapeutic approaches. Identification and isolation of cardiac- -specific stem/progenitor cells may deliver new perspectives for such therapy in the nearest future.
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[Functional improvement of injured retina following the adjuvant stem cell-based therapy. Preliminary report].
Klinika oczna. 01/2011; 113(4-6):117-21.
The purpose of this study was to appraise the functional response of damaged retina to the stem cell-based therapy in mice. The majority of disorders leading to the irreversible vision loss in the developed world is caused by retinal degeneration. Since, recent reports emphasized regenerative potent... [more] The purpose of this study was to appraise the functional response of damaged retina to the stem cell-based therapy in mice. The majority of disorders leading to the irreversible vision loss in the developed world is caused by retinal degeneration. Since, recent reports emphasized regenerative potential of bone marrow stem marrow stem/progenitor cells (SPCs), we investigated here the beneficial effect of intravenously administrated SPCs on regeneration of acutely injured retina. Selective chemical injury of murine retinas was induced by intravenous administration of sodium iodate (NalO3) in its toxic dose. Flash electroretinogram (ERG), was performed in different time points after infusion of bone marrow-derived and negative for linage antigens population of SPCs. Stem cell-based therapy resulted in gradual increase of b-wave amplitude in ERG recordings starting from the 3rd day after NalO3 administration, what confirmed the improvement of retinal function in long-term observation. Our preliminary findings revealed that the selected stem cell-based therapy employed in the adjuvant mode has been shown to be effective in supporting the retinal function recovery after acute retinal damage.
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1.97Impact points
Blood arachidonic acid and HDL cholesterol influence the phagocytic abilities of human monocytes/macrophages.
Annals of nutrition & metabolism. 11/2010; 57(2):143-9.
Many immunomodulators may intensify the process of phagocytosis in monocytes. Among them are the fatty acids contained in cellular membrane phospholipids. But in the available literature there are no reports on how blood fatty acids and lipoproteins can modulate the phagocytic abilities of cells. Th... [more] Many immunomodulators may intensify the process of phagocytosis in monocytes. Among them are the fatty acids contained in cellular membrane phospholipids. But in the available literature there are no reports on how blood fatty acids and lipoproteins can modulate the phagocytic abilities of cells. Therefore, the aim of this study was the evaluation of the phagocytic activity of monocytes isolated from the blood of healthy human subjects with defined fatty acids and lipoprotein content. Cells obtained from 24 donors were used for measuring phagocytic activity and for the quantification of serum fatty acids, total cholesterol, TG, HDL, and LDL, respectively. Phagocytosis was determined using a PHAGOTEST kit, fatty acids using a GC chromatograph, and lipids using test kits. The analysis shows an influence of serum HDL concentrations on the process of phagocytosis in the isolated cells and suggests that the concentration of arachidonic acid in blood is a factor that determines the phagocytic ability of monocytes. Moreover, the concentration of conjugated linoleic acid trans-10 cis-12 has considerable influence on phagocytosis.
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2.72Impact points
Sodium iodate selectively injuries the posterior pole of the retina in a dose-dependent manner: morphological and electrophysiological study.
Neurochemical research. 11/2010; 35(11):1819-27.
Sequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO(3)) were analyzed. Retinal morphology, apoptosis (TUNEL assay), and function (electroretinography; ERG) were examined at several time points after NaIO(3) ad... [more] Sequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO(3)) were analyzed. Retinal morphology, apoptosis (TUNEL assay), and function (electroretinography; ERG) were examined at several time points after NaIO(3) administration. The higher dose of NaIO(3) caused progressive degeneration of the whole retinal area and total suppression of scotopic and photopic ERG. In contrast, the lower dose induced much less severe degeneration in peripheral part of retina along with a moderate decline of b- and a-wave amplitudes in ERG, corroborating the presence of regions within retina that retain their function. The peak of photoreceptor apoptosis was found on the 3rd day, but the lower dose induced more intense reaction within the central retina than in its peripheral region. In conclusion, these results indicate that peripheral area of the retina reveals better resistance to NaIO(3) injury than its central part.
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3.48Impact points
Fluoride as a pro-inflammatory factor and inhibitor of ATP bioavailability in differentiated human THP1 monocytic cells.
Toxicology letters. 07/2010; 196(2):74-9.
Chronic exposure of humans to fluorine compounds in the air, water and food may be atherogenic via the activation of oxidative stress and increased ROS production. The most important factor that promotes the formation of ROS seems to be the oxidoreduction of electron carriers in the critical points ... [more] Chronic exposure of humans to fluorine compounds in the air, water and food may be atherogenic via the activation of oxidative stress and increased ROS production. The most important factor that promotes the formation of ROS seems to be the oxidoreduction of electron carriers in the critical points of the respiratory chain, which depends, among other things, on the cellular demand for ATP. This paper examines the effect of fluorides in concentrations determined in human serum on the intracellular synthesis of ROS, the activity of the respiratory chain enzymes and the synthesis of ATP via oxidative and substrate-level phosphorylation. The incubation of macrophages in fluoride solutions significantly decreased the amount of synthesized cellular ATP and increased formation of ROS and apoptosis in a dose-dependent pattern. The addition of respiratory chain inhibitors resulted in a significant decrease in the synthesized ROS. Sodium fluoride probably promotes oxidative stress in macrophages, which is manifested by a strong increase in ROS synthesis and a decrease in ATP. We suppose that fluoride may destabilize the action of respiratory chain. Our results indicate that the respiratory chain is the main site of ROS synthesis. One cannot exclude the stimulating role of fluorine compounds on the formation of ROS that is independent of the respiratory chain.
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1.26Impact points
Conjugated linoleic acids regulate triacylglycerol and cholesterol concentrations in macrophages/foam cells by the modulation of CD36 expression.
Acta biochimica Polonica. 01/2010; 57(3):379-84.
Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in ... [more] Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in food, e.g. linoleic acid and n-3 unsaturated fatty acids can modulate expression of CD36 on the macrophage surface. Conjugated linoleic acid isomers (CLA) that originate from the human diet, have demonstrated antiatherogenic properties in several experiments. Animal study evidenced that CLA could induce resolution of plaque by activation of peroxisome proliferator activated receptors and down-regulation of pro-inflammatory genes. Less unequivocal results were obtained in human studies (on the CLA effects on the inflammatory process). Therefore in this study we investigated the influence of CLA on CD36 expression and lipid accumulation in human macrophages. Macrophages were incubated with 30 μM cis-9,trans-11 CLA, trans-10,cis-12 CLA or linoleic acid for 48 h. After that, expression of CD36 as well as accumulation of lipids were measured by flow cytometry, microscopy and a spectroscopic method. We demonstrate that both cis-9,trans-11 C 18 : 2 CLA and linoleic acid slightly elevated expression of CD36, whereas second isomer — trans-10,cis-12 CLA — did not. Nevertheless, only trans-10,cis-12 CLA triggered delipidation of macrophages, that is decreased triacylglycerols concentration. Also in human adipocytes, trans-10,cis-12 CLA causes cell delipidation by reduction of PPAR receptor expression. We propose a similar mechanism for human macrophages/foam cells.
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[Physiological and pathological consequences of a presence of germ line stem cells in adult tissues].
Ginekologia polska. 12/2009; 80(12):935-41.
Various therapheutic strategies employing stem cells have been proposed as the alternative, effective methods for therapy of multitude diseases, difficult to treat using standard, well-established methods. Advancing regenerative medicine, which is becoming a novel branch of clinical medicine, has hi... [more] Various therapheutic strategies employing stem cells have been proposed as the alternative, effective methods for therapy of multitude diseases, difficult to treat using standard, well-established methods. Advancing regenerative medicine, which is becoming a novel branch of clinical medicine, has high hopes of stem cells which could be used in treatment of injuried organs such as myocardium after heart infarction, brain after stroke, spinal cord after mechanical injury as well as in treatment of diabetes and Parkinson disease. Application of embryonic stem cells, harvested from developing embryos, is highly controversial. Hence, the stem/primitive cells isolated from adult tissuses are considered to be an optimal source of cells for therapy. Recently our research team has isolated a population of very primitive stem cells from adult tissues (very small embryonic-like stem cells - VSELs) that show several embryonic-like features. These cells can become an alternative and more ethical source of the stem cells for therapy when compared to those isolated from the developing embryos.
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2.33Impact points
Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease.
Tissue antigens. 11/2009; 74(5):386-92.
Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrat... [more] Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.
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1.51Impact points
Potential application of adult stem cells in retinal repair--challenge for regenerative medicine.
Current eye research. 09/2009; 34(9):748-60.
Stem cells (SCs) maintain the balance among somatic cell populations in various tissues and are responsible for organ regeneration. The remarkable progress of regenerative medicine in the last few years indicates promise for the use of SCs in ophthalmic disorder treatment. This review describes the ... [more] Stem cells (SCs) maintain the balance among somatic cell populations in various tissues and are responsible for organ regeneration. The remarkable progress of regenerative medicine in the last few years indicates promise for the use of SCs in ophthalmic disorder treatment. This review describes the current view on hierarchy in the SC compartment and presents the latest attempts to use adult SCs in the regeneration of the retina. Research performed primarily in animal models gives hope for using similar strategies in humans. However, the search for the optimal source of SCs for cell therapy continues. We briefly discuss various potential sources of adult SCs that could be employed in regenerative medicine, particularly focusing on recently identified, very small embryonic-like SCs (VSEL-SCs). These cells are even present in the bone marrow and adult tissues of older patients and could be harvested from cord blood. We believe that VSEL-SCs, after the establishment of ex vivo expansion and differentiation protocols, could be harnessed for retina regeneration.
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0.99Impact points
Induction of mixed chimerism in mice by employing different conditioning protocols and bone marrow cell transplantation.
Transplantation proceedings. 07/2009; 41(5):1894-9.
Mixed chimerism has been suggested to produce allograft tolerance. Since this phenomenon is not fully understood, the aim of our study was to evaluate various protocols for chimerism induction in a mouse model. B6.SJL-Ptprc(a)Pep3(b) mice were injected with 20 to 30 x 10(6) bone marrow cells from Ba... [more] Mixed chimerism has been suggested to produce allograft tolerance. Since this phenomenon is not fully understood, the aim of our study was to evaluate various protocols for chimerism induction in a mouse model. B6.SJL-Ptprc(a)Pep3(b) mice were injected with 20 to 30 x 10(6) bone marrow cells from Balb C mice. Conditioning consisted of total body gamma irradiation with 9.5, 5, and 3 Gy on "-1 day" of the experiment, with 200 mg/kg cyclophosphamide (CP) ("+2 day"). Additionally, one group of mice received blocking antibody against CD40L on days 0, 1, 4, and 7. The presence of mixed chimerism in peripheral blood was assessed at 1, 2, 3, 4, 6, and 8 weeks using flow cytometry to detect CD45.1 or CD45.2 antigen expression. Moreover, the chimerism was examined in CD4, CD8, CD45/B220, Mac-1alpha subpopulations in peripheral blood and bone marrow cells at 8 weeks. We also compared chimerism in peripheral blood, bone marrow, and spleen leukocyte populations. We observed that the most effective conditioning method with relatively low toxicity was based on concomitant use of 5 Gy total body irradiation and CP. The percentage of donor cells differed among peripheral blood subpopulations and bone marrow cells, but was similar in leukocyte populations derived from various sources. Our experiments sought to optimize the induction of stable mixed chimerism.
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1.29Impact points
Elevated Plasma Levels of C3a Complement Compound in the Exudative Form of Age-Related Macular Degeneration.
Ophthalmic research. 06/2009; 42(1):54-59.
Aim: Recent findings suggest that chronic inflammatory processes play a role in the progression of age-related macular degeneration (AMD). Here we asked whether the development of different forms of AMD is connected with the elevation of plasma C3a-desArg concentration. Methods: We recruited 30 subj... [more] Aim: Recent findings suggest that chronic inflammatory processes play a role in the progression of age-related macular degeneration (AMD). Here we asked whether the development of different forms of AMD is connected with the elevation of plasma C3a-desArg concentration. Methods: We recruited 30 subjects with a clinical diagnosis of exudative AMD with newly diagnosed choroidal neovascularization (CNV), 30 subjects with dry AMD and 30 age- and sex-matched volunteers without AMD. The concentration of C3a-desArg complement compound was measured in the subjects' peripheral blood. We evaluated the association between the level of C3a-desArg and age, sex, smoking, atherosclerosis, and hypertension. Results: We found that the levels of C3a-desArg were significantly elevated in patients with exudative AMD compared to the control group. The concentrations of C3a-desArg in patients with dry AMD were similar to those of controls. Additionally, patients and controls with documented atherosclerosis (AS) displayed significantly higher levels of C3a-desArg compared to subjects without AS. Conclusions: Our results suggest an association between systemic complement activation and the development of CNV. Moreover, we found an association of complement activation with atherosclerosis and confirmed the hypothesis that AMD can be a local manifestation of systemic disease.
Following (8)
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Jolanta Tarasiuk
University of Szczecin -
Aldona Siennicka
Pomeranian Medical University in Szczecin -
Tomasz Huzarski
Pomeranian Medical University in Szczecin -
Dariusz Chlubek
Pomeranian Medical University in Szczecin, Poland -
Irena Baranowska-Bosiacka
Pomeranian Medical University in Szczecin
75
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