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At least 1,513 records · Page 84Linked to original sources
PubMed2005

[The medicinal serum of yi-shen ruan-jian san antagonized the effect of aristolochic acid on human proximal tubular epithelial cells in vitro].

OBJECTIVE: To evaluate whether the medicinal serum of Yi-shen Ruan-jian san can antagonize the fibrogenic effect of human proximal tubular epithelial cell line (HKC) activated by aristolochic acid (AA) in vitro. METHOD: The HKC was incubated in the media containing 40 mg x L(-1) aristolochic acid sodium salt (AA-Na) with or without 10% concentration of Yi-shen Ruan-jian san medicinal serum. Then the cell proliferation and cytotoxicity of HKC were determined by MTF and lactate dehydrogenase (LDH) release assay respectively, the antigen expression of cytokeratin and alpha-smooth muscle actin on HKC was detected by immunocytochemistry, the mRNA expression of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type I Collagen (Col I) of HKC was measured by RT-PCR, and their protein expression was measured by ELISA or Western blot. RESULT: No cytotoxic effect was found in HKC after stimulation of AA-Na with or without the medicinal serum of Yi-shen Ruan-jian san (P > 0.05). No epithelial-myofibroblast transdifferentiation was found in HKC after AA-Na stimulation. The mRNA and protein expression of TGF-beta1, CTGF, PAI-1 and TIMP-1 of HKC was significantly upregulated by AA-Na (P < 0.05). The above-mentioned enhanced mRNA and protein expression, except for PAI-1, was significantly downregulated by the medicinal serum of Yi-shen Ruan-jian san, compared with the control (normal rat serum in the same concentration) (P < 0.05). CONCLUSION: The fibrogenic effects of HKC activated by AA are antagonized by Yi-shen Ruan-jian san, through downregulating the expression of promoting excellular matrix (ECM) synthesis factors (TGF-beta1, CTGF) and inhibiting ECM degradation factor (TIMP-1).

Animals↗
PubMed2005

Yolk sac carcinoma derived from the rat epiblast as a renal isograft.

We report the novel observation that a biphasic, parieto-visceral (PYS/VYS) yolk sac carcinoma can develop from the isolated epiblast of the pre-primitive streak rat embryo in a prolonged cultivation in vivo as a renal isograft. Late 7-day rat egg cylinders were dissected free of the ectoplacental cone and the Reichert's membrane. The middle segment of the cylinder, in which the embryonic and the extraembryonic cell layers partly overlap, were also removed. From the rest of the cylinder the 4 cell layers were isolated and transplanted separately under the kidney capsule of isogenic adult males. After 4 weeks the hypoblast was resorbed, the extraembryonic ectoderm gave rise to hemorrhagic cysts and trophoblastic giant cells, the extraembryonic (visceral yolk sac) endoderm formed benign cystic PYS/VYS tumors, and the epiblast developed into a benign teratoma. After prolonged (7-30 weeks) development of these teratomas as isografts, a malignant yolk sac carcinoma (YSC) developed in 45% of them. It destroyed the teratoma and the recipient's kidney, metastasized to peritoneum and other sites, and caused abundant ascites containing clustered tumor cells. The primary tumor was retransplantable subcutaneously as well as intraperitoneally, and displayed the characteristics of the mixed or biphasic PVYS carcinoma, with a progressive loss of the VYS component with time. Several data are apparently in favor of its origin by transdifferentiation rather than from undifferentiated cells.

Animals↗
PubMed2005

[Adult stem cells: who are they, what do they do?].

Fascinating and provocative findings have shaken the stem cell research field in recent years. One unexpected discovery is the identification of stem/progenitor-like cells in many tissues with slow cellular turnover, such as heart, kidney, muscle and brain. Cells with high proliferative capacity and multilineage differentiation potential have also been described in bone marrow, although their existence needs to be confirmed. Both cell types may prove to have therapeutic potential, but research on their use for tissue repair has been rather disappointing. In addition, serious doubts have been raised concerning the transdifferentiation potential of hematopoietic stem cells, underlining the need for care when interpreting findings that question long-established concepts.

Adult↗
PubMed2005

[Role of stem cells in cardiac repair].

The use of stem cells for cardiac repair is based on their potential to become cardiomyocytes and thereby to restore the functional capacity of the failing heart. The concept of transdifferentiation, by which adult stem cells adopt the fate of the cells they are intended to replace, generated enormous enthusiasm, but it is increasingly recognized that the plasticity of these cells is rather limited. This is particularly the case of skeletal myoblasts, which remain committed to their myogenic lineage. Likewise, conversion of bone marrow-derived cells into cardiomyocytes is, at most, an exceptional and quantitatively limited event. These limitations do not preclude the possibility that adult stem cells could have protective effects on left ventricular function, possibly through a paracrine action. Tissue-resident cardiac stem cells were recently identified but significant hurdles will have to be overcome if they are to be used for therapeutic purposes. Consequently, much hope is currently being placed in embryonic stem cells which, provided they are appropriately precommitted during culture, can differentiate into cardiomyocytes. Their subsequent electromechanical integration into the recipient myocardium can contribute to the repair of the damaged heart.

Heart Diseases↗
PubMed2005

[Liver repopulation strategies].

Hepatocytes have the unique capacity to self-renew and repair the liver ad integrum when stimulated to proliferate by liver injury. However, transplantation of isolated hepatocytes is usually not sufficiently efficient for therapeutic purposes. We conferred a survival advantage on transplanted hepatocytes and showed that they were able to repopulate almost the entire mouse liver after repeated injury. In contrast, we found that bone marrow stem cell transdifferentiation was inadequate for therapeutic liver regeneration. Current data on liver stem cells will be discussed.

Animals↗
PubMed2005

[The differentiation potential of stem cells (the problem of plasticity)].

Numerous publications on the ability of adult stem cells to differentiate into the cells of various tissues, not always homodermic (stem cell flexibility), to contain serious methodic errors. The main flexibility phenomena, such as "transdifferentiation" of hemopoietic stem cells into hepatocytes, cardiomyocytes, beta-cells of islets of Langerhans, neurons etc., are caused not by a shift of the differentiation path, but by cell merging, resulting in appearance of hybrids with unusual markers of cells of non-hemopoietic origin. The second most frequent error is wrong identification of macrophages and lymphocytes, which are present in any tissue and have the donor's genotype in chimeras. Even when the cause of the error is unknown, the phenomenon of unusual cell formation is exclusively rare and never bears therapeutic potential. In general, it is at least too early to revise the main tenets of the stem cell doctrine. Embryonic stem cells are totipotent indeed; however, the time of their clinical use has not come yet. Attempts to induce their ordered differentiation keep on failing; they very often lead to formation of teratomas and, even if necessary cells such as hemopoietic stem cells are formed, they do not work after administration into an organism that has been exposed to radiation. Clinical use of embryonic stem cells do not seem possible in this decade.

Bone Marrow↗
PubMed2005

[The role of TGF-beta1/Smads in the development of peritoneal fibrosis induced by high glucose peritoneal dialysate and LPS].

OBJECTIVE: To investigate the expression and the potential role of TGF-beta/Smads in peritoneal fibrosis induced by high glucose dialysate and LPS in rats. METHODS: 24 male Sprague-Dawley rats were randomly allocated into four groups: control group, normal rats; LPS group: rats were treated with intraperitoneal injection of LPS (0.6 mg/kg body weight) on days 1, 3, 5, 7; dialysate Group: rats were treated with daily intraperitoneal injection of 4.25% peritoneal dialysate (100 ml/kg body weight) for 4 weeks; LPS + dialysate Group: daily intraperitoneal injection of 4.25% dialysate combined with four times injection of LPS (0.6 mg/kg body weight on days 1, 3, 5, 7) for 4 weeks. The parietal thickness was measured with masson stain. The expression of alpha-SMA, TGF-beta1, Smad 2/3, Smad 7 and ColI in peritoneal membrane was detected with confocal microscope by immuno-fluorescence, Western-blot and RT-PCR. RESULTS: Masson stain show the parietal thickness of the rats in all groups was significantly increased compared with control group and collagen deposition was evident in the thickened submesothelial compact zone. Parietal thickness of the rats in LPS + dialysate Group was most (vs LPS group: 41.5 +/- 3.3 microm vs 34.70 +/- 3.6 microm, P = 0.007, vs dialysate Group, 41.5 +/- 3.3 microm vs 20.2 +/- 3.6 microm, P = 0.000). The expression of alpha-SMA, Col I, TGF-beta1, Smad 3 was up-regulated in protein and mRNA level and the protein level of phosphorylated-Smad 2/3 was increased significantly. The most significant changes were found in LPS + dialysate Group. Compared with control group the mRNA and protein level of Smad7 was increased, but the protein ratio of phosphorylated Smad/Smad 7 in all groups was higher. Under electro-microscope, the mesothelial cells in LPS + dialysate Group had myofibroblast morphology with the presence of large bundles of actin microfilaments and dense bodies within the cytoplasm. CONCLUSIONS: High concentration glucose dialysate or LPS contributes to peritoneal fibrosis by stimulating TGF-beta/Smads signaling. 4.25% peritoneal dialysate can coordinate with LPS to activate TGF-beta/Smads signaling pathway and induce mesenchymal transdifferentiation and peritoneal fibrosis.

Animals↗
PubMed2005

Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes.

Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC). These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI) with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD). There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens), as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear cells. The maximum number of stem cells was found early in ST-segment elevation myocardial infarction (<12 hours) with subsequent decrease through the 7-day follow-up and with concomitant changes in the levels of cytokines involved in the inflammatory response and stem cell recruitment. Moreover, peak expression of cardiac muscle and endothelial markers occurred at the same time as the most significant increase in CD34/CXCR4+ stem cell number. The SDF-1/CXCR-4 axis seems particularly important in stem/muscle progenitor cell homing, chemotaxis, engraftment and retention in ischaemic myocardium. The significance of autologous stem cells mobilization in terms of cardiac salvage and regeneration needs to be proved in humans but it seems to be a reparative mechanism triggered early in the course of acute coronary syndromes.

Acute Disease↗
PubMed2005

Clinical trials using autologous bone marrow and peripheral blood-derived progenitor cells in patients with acute myocardial infarction.

This paper discusses the current data concerning the results of major clinical trials using bone marrow-derived and peripheral blood-derived stem/progenitor cells in treatment of patients with acute myocardial infarction (AMI) and depressed left ventricular ejection fraction. In all major trials (TOPCARE-AMI, BOOST), the primary outcome measure was increase in left ventricular systolic function (LVEF) and left ventricle remodeling. The most consistent finding is the significant increase in LVEF. Some trials suggest also reduction of left ventricular remodeling. Although the absolute LVEF increase is small (6-9%), it may substantially contribute to the improvement of global LV contractility. None of the studies in AMI patients treated with intracoronary infusion of progenitor cells revealed excess risk of arrythmia, restenosis or other adverse effects attributable to the therapy. The exact mechanism of improved myocardial contractile function remains unknown, however, there are several possible explanations: therapeutic angiogenesis improving the blood supply to the infarct border zone, paracrine modulation of myocardial fibrosis and remodeling (e.g. inhibition of myocyte apoptosis) and transdifferentiation of stem/progenitor cells into functional cardiomyocytes. No study showed the superiority of the particular subpopulation of autologous progenitor cells in terms of left ventricular function improvement in AMI. In fact, most of the clinical trials used the whole population of mononuclear bone marrow-derived progenitor cells, peripheral blood derived progenitor cells (endothelial progenitors).

Acute Disease↗
PubMed2005

[Present view on the stem cell plasticity and cell therapy].

The most controversial problem in the present biology and medicine is the existence of stem cell plasticity. Experimental biology and medicine have been working with stem cells and stem cell therapy more than twenty years. The term plasticity, as it is understood, is the potential of stem cell phenotypes that is much broader that phenotypes of differentiated cells of their original tissues. Many laboratories have documented the existence of stem cell plasticity; however, many objections to the reported results still exist. Here, we present some of these objections questioning the data on stem cell plasticity. We wish to point out some problems associated with plasticity of stem cells, transdifferentiation and cell fusion. Recent experimental results indicate that stem cells may have a key role in stem cell therapy. This review is an introductory discussion on the stem cell plasticity and stem cell therapy.

Animals↗
PubMed2006

Pyloric gland adenoma-- how to diagnose?

The term "pyloric gland adenoma" reflects its etiogenesis from deep mucoid glands in the stomach. The diagnosis can be confirmed by immunohistochemistry. Typically, pyloric gland adenomas are strongly positive for Mucin 6 (deep mucoid gastric glands). These lesions express Mucin 6 over the whole lesion up to the surface often only with a small layer of columnar epithelium expressing Apomucin 5AC. The amount of mucin 5AC which is expressed on normal within the apical foveolar epithelium might vary from case to case. Combination or transdifferentiation with ordinary tubular (intestinal differentiation) adenoma can be observed. The gastric corpus mucosa of elderly female patients with autoimmune gastritis is highly affected. The frequency of pyloric gland adenoma is given in the literature being 2.7% of all gastric polyps. Therefore pyloric gland adenomas are not that rare that one might assume. Only a few publications are available which makes one think that these lesions are frequently misinterpreted. Pyloric gland adenomas can arise in gastric heterotopia and gastric metaplasia in the whole gastrointestinal tract. The clinical significance is given by a 30% rate of malignant transformation. These cases represent for the most well differentiated early adenocarcinomas which are known to have an excellent prognosis after complete polypectomy and limitation to the mucosal layer.

Adenoma↗
PubMedDate not supplied

Ex vivo analysis of dialysis effluent-derived mesothelial cells as an approach to unveiling the mechanism of peritoneal membrane failure.

During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids, which causes progressive fibrosis and angiogenesis and, ultimately, ultrafiltration failure. In addition, repeated episodes of peritonitis or hemoperitoneum may accelerate all these processes. Fibrosis has been classically considered the main cause of peritoneal membrane functional decline. However, in parallel with fibrosis, the peritoneum also displays increases in capillary number (angiogenesis) and vasculopathy in response to PD. Nowadays, there is emerging evidence pointing to peritoneal microvasculature as the main factor responsible for increased solute transport and ultrafiltration failure. However, the pathophysiologic mechanism(s) involved in starting and maintaining peritoneal fibrosis and angiogenesis remain(s) elusive. Peritoneal stromal fibroblasts have been considered (for many years) the cell type mainly involved in structural and functional alterations of the peritoneum; whereas mesothelial cells have been considered mere victims of peritoneal injury caused by PD. Recently, ex vivo cultures of effluent-derived mesothelial cells, in conjunction with immunohistochemical analysis of peritoneal biopsies from PD patients, have identified mesothelial cells as culprits, at least in part, in peritoneal membrane deterioration. This review discusses recent findings that suggest new peritoneal myofibroblastic cells may arise from local conversion of mesothelial cells by epithelial-to-mesenchymal transition during the repair responses that take place in PD. The transdifferentiated mesothelial cells may retain a permanent mesenchymal state, as long as initiating stimuli persist, and contribute to PD-induced fibrosis and angiogenesis, and hence to membrane failure. Future therapeutic interventions could be designated in order to prevent or reverse epithelial-to-mesenchymal transition of mesothelial cells, or its pernicious effects.

Biological Transport↗
PubMed2006

Interleukin-4 differentially regulates osteoprotegerin expression and induces calcification in vascular smooth muscle cells.

Vascular calcification is characterized by cellular transdifferentiation and expression of bone-related matrix proteins that result in the presence of bone-like structures in the vascular wall. Interleukin (IL)-4, a pleiotropic cytokine, and osteoprotegerin (OPG), an essential regulator of osteoclast biology, have both been linked to vascular disease. Here, we assessed the role of IL-4 and OPG in vascular calcification in vitro. IL-4 induced OPG mRNA levels and protein secretion by 5-fold in a dose- and time-dependent fashion in human coronary artery smooth muscle cells (CASMC). Activation of the transcription factor STAT6 preceded IL-4-induced OPG expression, and blockade of IL-4-induced STAT6 activation by the phospholipase C inhibitor D609 decreased OPG expression. Long-term exposure of IL-4 for 4 weeks resulted in transformation of CASMC towards an osteoblastic phenotype, based on the expression of the transcription factor Cbfa1 and increased mineral deposition. Notably, calcification of CASMC was inhibited by gene silencing of Cbfa1. During osteogenic transformation, IL-4 down-regulated OPG production in CASMC. IL-4 has differential effects in CASMC: While short-term exposure enhances OPG production through a STAT6-dependent mechanism, long-term exposure causes Cbfa1-dependent osteogenic transformation and a decreased production of OPG, an inhibitor of bone resorption.

Bone Resorption↗
PubMed2005

Expression of cytoskeletal proteins in hepatic stellate cells isolated from normal and cirrhotic rat liver.

Hepatic stellate cells (HSC) are located in Disse spaces of normal rat liver. In their quiescent state they serve as a storage site for vitamin A. In fibrotic liver they become activated, proliferate and they undergo transdifferentiation into myofibroblast-like cells. Changes in the cell phenotype are accompanied by changes in the cellular cytoskeleton. We have studied the expression of alpha-smooth muscle actin and intermediate filament proteins vimentin, desmin and glial fibrillary acidic protein (GFAP) by immunocytochemistry in HSC cultured for 2 or 7 days after isolation. Normal or cirrhotic rat liver was perfused with solutions of pronase and collagenase and HSC were isolated by density gradient centrifugation of the resulting cell suspension. Liver cirrhosis was produced in rats by repeated carbon tetrachloride administration. Vimentin was detected in all cells from normal and cirrhotic liver. The concentration of desmin in the cells from cirrhotic liver was slightly higher than that in normal cells and it increased with time in culture. GFAP could be detected only in normal cells 2 days after their isolation. In contrast, alpha smooth muscle actin (alpha-SMA) was absent from normal cells at this time but its expression was pronouced later. In most cells from cirrhotic liver this antigen was already present on the second day of culture and its expression further increased.

Animals↗
PubMed2006

[Differentiation potential of stem cells from bone marrow].

Hematopoietic organs such as bone marrow contain various stem and progenitor cells with a differentiation capability exceeding hematopoiesis, a process also referred to as plasticity. Stem cells in bone marrow are hematopoietic stem cells, mesenchymal stem cells, and multipotent progenitor cells. Several examples for the development of stem cells of hematopoietic organs into nonhematopoietic tissue open novel ways in regenerative medicine. Animal experiments showed generation of neuronal tissue, cardiomyocytes and functional hepatocytes in injured tissue from bone marrow stem cells. Interpreting these results one has to keep in mind that besides transdifferentiation also cell fusion or heterogeneous stem cell populations might contribute to tissue regeneration. First clinical studies on therapy with bone marrow stem cells in myocardial infarction or liver embolization showed promising results.

Antigens, CD34↗
PubMed2006

[Mobilization of stem cells in cardiovascular disease. Improvement of vascularization, cardiac function and arrhythmias].

Besides re-injecting mostly autologous stem cells also the mobilization of stem cells from the bone marrow is increasingly evaluated. Mobilization of bone marrow cells can be induced by drugs, e.g., growth factors, or by physical exercise. Exercise leads to a number of physiological cardiopulmonary changes, and an improved vascularization of the heart and skeletal muscle, initiated by endothelial progenitor cells derived from the bone marrow. Particularly, duration exercise activates not only the release of CD34-positive cells, it also leads to increased pro- and anti-inflammatory cytokines, granulocyte colony-stimulating factor (G-CSF) being one of them. Originally, it was believed that therapeutic effects following bone marrow mobilization were based on the homing and transdifferentiation of bone marrow cells into cardiomyocytes, new data support the notion that the most important mechanism might be via paracrine and/or direct effects of G-CSF.

Antigens, CD34↗
PubMed2006

[Mesenchymal stem cells for cardiac regeneration].

Since physiological regeneration of cardiac muscle is limited, scar tissue replaces damaged myocardial tissue leading to impaired cardiac function. Whether stem cell therapy can prevent this process and regenerate cardiac tissue is the issue of many research projects at present. Some studies investigate mesenchymal stem cells (MSC) from bone marrow, which are known to have the potential to differentiate into various tissues. Under certain conditions the formation of cardiomyocytes was observed in vitro and in vivo, which, however, is a controversial issue. Nevertheless many investigators found an improvement of cardiac function after transplantation of MSC into damaged heart tissue. Since only few cells survive mid-term after transplantation, the impact of real cell replacement might be limited. Instead of or besides the replacement of lost cells by transdifferentiated MSC, the secretion of paracrine factors by MSC may be important for functional improvement. Thus, MSC show promising experimental results, and may be of therapeutic value for heart disease in the future. However, there are many unanswered questions and problems, which need to be resolved before.

Animals↗
PubMed2006

Journey from hepatocyte transplantation to hepatic stem cells: a novel treatment strategy for liver diseases.

Acute liver failure (ALF) carries high morbidity and mortality (>80%) even in the best centres. Orthotopic liver transplantation (OLTx) is the only viable approach to the treatment of ALF. This has significantly improved the survival in these patients. The major limitations of OLTx are non availability of the donor liver, requirement of a major surgical procedure, high cost and longterm immunosuppression. Isolated hepatocyte transplantation is emerging as an appealing method for the treatment of ALF because of its technical simplicity and easy availability of cells. Transplantation of allogenic/xenogenic hepatocytes transplantation in experimentally induced ALF has shown an increased survival rate. Clinical studies in acute, chronic liver failure and metabolic disorders have also been undertaken in a few centres and have shown encouraging results. To maintain the continuous supply of cells, xenogenic source of hepatocytes (porcine, rabbit, canine) have offered a hope. A major concern regarding the use of xenogenic donors is the risk of transmission of zoonosis and immunogenicity. Recently, Porcine endogenous retrovirus (PERV) has been shown to infect human tissue in vitro. The problem of immunogenicity of xenogenic hepatocytes can be overcome to some extent by immunoisolation, encapsulation technique, which may also provide protection to the hepatocytes during cryopreservation. The knowledge of adult hepatic stem from tissue offered a new hope for the treatment of various chronic and metabolic diseases. Further, the transdifferentiation potentiality of haematopoietic stem cells to hepatic lineage has strengthened cell therapy.

Animals↗