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At least 1,063 records · Page 59Linked to original sources
PubMed2000

Vasopressin-induced hypertrophy in H9c2 heart-derived myocytes.

Protein synthesis in H9c2 heart-derived myocytes responds biphasically to arginine vasopressin (1 microM). An initial 50% inhibition attributable to Ca(2+) mobilization from the sarcoplasmic/endoplasmic reticulum is followed by a recovery that subsequently converts to a 1.5-fold stimulation. This study was undertaken to ascertain whether vasopressin programs H9c2 cells to undergo hypertrophy or to proliferate and whether early translational inhibition is required for programming. Translational suppression was observed only at vasopressin concentrations (>1 nM) causing extensive (>50%) depletion of Ca(2+) stores and was diminished at supraphysiologic extracellular Ca(2+) concentrations. Stimulation of protein synthesis, by contrast, was unaffected by changes in extracellular Ca(2+), depended on gene transcription, was suppressed by a protein kinase C pseudosubstrate sequence (peptide 19-27), and was observed at pM vasopressin concentrations. Activation of MAP kinases, phosphoinositide 3-kinase, calcineurin, S6 kinase, or eIF4 could not be implicated in the stimulation, which persisted for 24 h. Vasopressin-treated H9c2 cells underwent hypertrophy by standard criteria. Cellular protein accumulation occurred at pM hormone concentrations, was blocked by peptide 19-27, was observed regardless of retinoic acid pretreatment to prevent myogenic transdifferentiation, and preceded full repletion of Ca(2+) stores. It is proposed that H9c2 cells, which possess all basic features of V1-vasopressin receptor signaling, provide a convenient model for investigating vasopressin-induced myocyte hypertrophy. Early translational suppression is not needed for vasopressin-induced H9c2 myocyte hypertrophy whereas activation of protein kinase C appears essential.

Animals↗
PubMed2003

Stem cell research need not be carried out utilizing human embryos.

Stem cells still lack integral and exhaustive legislation in Italy and in the European Union. The use of pluripotent embryonic stem cells (ESC) for cell therapy seems to be encumbered with several disadvantages, such as the frequency of aneuploidy and the risk of tumour development (i.e. formation of teratomes). In addition, the capacity for indefinite growth of ESC, which first seems to confer them an advantage, may become potentially harmful if some ESC contaminate the transplantation of their derived differentiated cells. This is, in part, contrasted by the ease of obtaining and expanding adult or cord blood-derived stem cells in vitro, and by their transdifferentiation capacity (the so-called somatic stem cell 'plasticity'). Moreover, ethical considerations make us plead against the use of human embryos for stem cell research. First and foremost, there is the ethical position that it is never permissible to stop human life in order to prolong human life, except in self-defence. We must maintain that a human embryo certainly constitutes a new human life with the direct potential of one day becoming a human infant. Therefore, human embryo should not be considered just a 'cluster of cells' but a 'person'. Humanity is at a philosophical crossroads and we need to speak up in favour of the dignity of human life from its very inception.

Bioethics↗
PubMed2002

Cell therapy of heart failure.

Together with angiogenesis and gene therapy, cell transplantation is one of the newest treatments that have been proposed to improve the still grim outcome of patients with cardiac failure. The underlying rationale is that implantation of contractile cells into fibrous post-infarction scar can functionally 'regenerate' these areas. Primarily for practical reasons, autologous skeletal myoblasts have been the first to be tested in a clinical trial but other cell types can be considered, among which bone marrow stromal and hematopoietic stem cells are of particular interest because of their autologous origin and their purported transdifferentiation potential into cardiac and/or endothelial cells. However, several key issues still need to be addressed, including (i) the optimal type of donor cells, (ii) the mechanism by which cell engraftment improves cardiac function, actively (i.e., by increasing contractility) or passively (i.e. by limiting infarct expansion and remodelling), (iii) the optimisation of cell survival, and (iiii) the potential benefits of cell transplantation in non-ischaemic heart failure. Parallel to the numerous experimental studies designed to address these issues, initial clinical trials are underway or in preparation and, if properly designed and conducted, should allow to know whether the hopes raised by cellular therapy are met by clinically meaningful improvements in the outcomes of patients with heart failure.

Animals↗
PubMed2002

Medical perspectives of adults and embryonic stem cells.

In the last 30 years, allogeneic bone marrow transplantation has become the treatment of choice for many hematologic malignancies or inherited disorders and a number of changes have been registered in terms of long-term survival rate of transplanted patients as well as of available sources of hematopoietic stem cell (HSC). In parallel to the publication of better results in HSC transplantation, several recent discoveries have opened a scientific and ethical debate on the therapeutical potential of stem cells isolated from adult or embryonic tissues. One of the major discoveries in this field is the capacity of bone marrow-derived stem cells to treat a genetic liver disease in a mouse model, thus justifying the concept of transdifferentiation of adult stem cell and raising hopes on its possible therapeutical applications. We have tried here to summarise the advances in this field and to discuss the limits of these biological data.

Adult↗
PubMed2006

Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest.

Metazoans are composed of a finite number of recognisable cell types. Similar to the relationship between species and ecosystems, knowledge of cell type diversity contributes to studies of complexity and evolution. However, as with other units of evolution, the cell type often resists definition. This review proposes guidelines for characterising cell types and discusses cell homology and the various developmental pathways by which cell types arise, including germ layers, blastemata (secondary development/neurulation), stem cells, and transdifferentiation. An updated list of cell types is presented for a familiar, albeit overlooked model taxon, adult Homo sapiens, with 411 cell types, including 145 types of neurons, recognised. Two methods for organising these cell types are explored. One is the artificial classification technique, clustering cells using commonly accepted criteria of similarity. The second approach, an empirical method modeled after cladistics, resolves the classification in terms of shared features rather than overall similarity. While the results of each scheme differ, both methods address important questions. The artificial classification provides compelling (and independent) support for the neural crest as the fourth germ layer, while the cladistic approach permits the evaluation of cell type evolution. Using the cladistic approach we observe a correlation between the developmental and evolutionary origin of a cell, suggesting that this method is useful for predicting which cell types share common (multipotential) progenitors. Whereas the current effort is restricted by the availability of phenotypic details for most cell types, the present study demonstrates that a comprehensive cladistic classification is practical, attainable, and warranted. The use of cell types and cell type comparative classification schemes has the potential to offer new and alternative models for therapeutic evaluation.

Evolution, Molecular↗
PubMed1999

The expression of the fibrillar collagen genes during fracture healing: heterogeneity of the matrices and differentiation of the osteoprogenitor cells.

The cells that express the genes for the fibrillar collagens, types I, II, III and V, during callus development in rabbit tibial fractures healing under stable and unstable mechanical conditions were localized. The fibroblast-like cells in the initial fibrous matrix express types I, III and V collagen mRNAs. Osteoblasts, and osteocytes in the newly formed membranous bone under the periosteum, express the mRNAs for types I, III and V collagens, but osteocytes in the mature trabeculae express none of these mRNAs. Cartilage formation starts at 7 days in calluses forming under unstable mechanical conditions. The differentiating chondrocytes express both types I and II collagen mRNAs, but later they cease expression of type I collagen mRNA. Both types I and II collagens were located in the cartilaginous areas. The hypertrophic chondrocytes express neither type I, nor type II, collagen mRNA. Osteocalcin protein was located in the bone and in some cartilaginous regions. At 21 days, irrespective of the mechanical conditions, the callus consists of a layer of bone; only a few osteoblasts lining the cavities now express type I collagen mRNA. We suggest that osteoprogenitor cells in the periosteal tissue can differentiate into either osteoblasts or chondrocytes and that some cells may exhibit an intermediate phenotype between osteoblasts and chondrocytes for a short period. The finding that hypertrophic chondrocytes do not express type I collagen mRNA suggests that they do not transdifferentiate into osteoblasts during endochondral ossification in fracture callus.

Animals↗
PubMed2000

Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse.

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Acute Disease↗
PubMed2002

Possible participation of endotoxin of gram-negative bacteria in pathogenesis of liver damage during viral hepatitis.

Possible role of gram-negative bacteria in the genesis of hepatic damage during chronic viral hepatitis B and C was studied. Histological activity, hepatocyte proliferative activity, and expression of alpha-smooth muscle actin were compared with the severity of endotoxemia in patients with chronic hepatitis B and C. The study revealed a correlation between the degree of intralobular necroses, hepatocyte proliferation, and myofibroblast transdifferentiation of Ito cells with endotoxin concentration in the blood.

Biopsy, Needle↗
PubMed2003

Angiogenesis is not mediated by prostate cancer neuropeptides.

Once metastatic, prostate cancer (CaP) treatment options are limited to androgen withdrawal. In this environment, the cells often develop an androgen independent state resulting in patient demise. It has been shown that during this transition, CaP cells transdifferentiate to neuroendocrine cells, which produce neuropeptides. These neuropeptides have a mitogenic effect on surrounding CaP cells. Previous observations suggest that endothelial cells may show a similar mitogenic response to neuropeptides, implicating angiogenesis in the progression of CaP. We stimulated human umbilical endothelial cells (HUVECs) with the neuropeptides bombesin and neurotensin and measured proliferation, migration, cell tube formation, and tyrosine kinase activation. In our studies, neurotensin and bombesin did not stimulate HUVEC proliferation, migration, nor tube formation. Although HUVECs express the non-receptor tyrosine kinases Fak, Src, and Etk which mediate neuropeptide signaling in CaP, they are not activated by neuropeptides in HUVECs.

Blotting, Western↗
PubMed2002

The involvement of galectin-1 in skeletal muscle determination, differentiation and regeneration.

The dogma that a cell is rigidly committed to one tissue type has been heavily challenged over the past few years with numerous reports of transdifferentiation of cells between different lineages. Cells capable of entering lineages other than that of their tissue of origin have been identified in several diverse tissues. Recently we have focussed on a non-committed myogenic cell within the dermis that is capable, under certain conditions, of expressing muscle specific markers and even fusing to the terminally differentiated stage of muscle cell development. We have identified galectin-1 as being a potent factor implicated in this process. In this review we discuss our findings and consider the involvement of galectin-1 in muscle determination, differentiation and regeneration.

Animals↗
PubMed2002

Mesenchymal cells in the liver--one cell type or two?

The wall of the liver sinusoid is made of highly specialized cells, the hepatic stellate cells (HSC) which together with the sinusoidal endothelial cells represent a loose barrier to the corpusculate part of the blood flowing through the liver. Quiescent stellate cells (quiescent HSC) store Vitamin A; "activated" stellate cells become involved in the reaction to acute or chronic noxae damaging the liver parenchyma. Activated HSC show increased protein synthesis capacity, increased DNA-synthesis and acquire a myofibroblast-like phenotype. Under similar conditions liver myofibroblasts (MF) of the portal field and of the pericentral area may also become "activated" by increasing protein synthesis, DNA synthesis and cell division. They express the fibulin-2 gene and produce large amounts of IL-6. In contrast to "activated" HSC they do not undergo spontaneous apoptosis in vitro and do not express the CD95-ligand gene. So far no definite prove has been found for a "transdifferentiation" of HSC to myofibroblasts. On the contrary an increasing amount of data support the conviction that HSC and MF represent two similar but not identical cell populations the latter being comparable to those of other organs.

Animals↗
PubMed2003

Post-transplant renal tubulitis: the recruitment, differentiation and persistence of intra-epithelial T cells.

Tubulitis is used by the Banff protocol as a major criterion to grade acute renal allograft rejection. This review integrates results from in vitro and in vivo studies to develop a chronological model to explain the development and functions of tubular inflammation during the rejection process. Proteoglycan-immobilized chemokines are the primary motivators for the vectorial recruitment of specific immune cell populations from the blood, through the endothelium and interstitial tissues to the renal tubules. After penetration of the basement membrane, T cells encounter TGF-beta that can induce expression of the alphaEbeta7 integrin on proliferating cells. This allows adhesion to E-cadherin on the baso-lateral surfaces of tubular epithelial cells and provides an explanation for the epithelial-specific cytotoxicity observed during acute rejection. Tubular epithelium is also a rich source of IL-15 that can stimulate IL-15 receptor-expressing intratubular CD8+ T cells. This anti-apoptotic microenvironment may explain the long-term persistence of cycling T cells within intact tubules after episodes of acute rejection. These memory-like T cells may have local immunoregulatory properties, including the production of additional TGF-beta, but could also modify normal tubular homeostasis resulting in epithelial to mesenchymal transdifferentiation, tubulointerstitial fibrosis and, ultimately, graft failure.

Graft Rejection↗
PubMed2000

Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.

The characterization of hepatic progenitor cells is of great scientific and clinical interest. Here we report that intravenous injection of adult bone marrow cells in the FAH(-/-) mouse, an animal model of tyrosinemia type I, rescued the mouse and restored the biochemical function of its liver. Moreover, within bone marrow, only rigorously purified hematopoietic stem cells gave rise to donor-derived hematopoietic and hepatic regeneration. This result seems to contradict the conventional assumptions of the germ layer origins of tissues such as the liver, and raises the question of whether the cells of the hematopoietic stem cell phenotype are pluripotent hematopoietic cells that retain the ability to transdifferentiate, or whether they are more primitive multipotent cells.

Animals↗
PubMed1989

The multipotential cells of the limbus.

Ample evidence exists that there is a centripetal movement of cells from the periphery of the cornea toward the centre. While conjunctival cells have the capacity to transdifferentiate into corneal epithelial cells, the limbal region appears to act as a barrier between the conjunctival and corneal epithelia, even after large epithelial defects are created. The existence of limbal stem cells is suggested by the apparent role of the limbus in acting as a source of peripheral corneal cells. While specific staining of limbal cells has been reported in the rabbit, there is no positive identification of such stem cells in the human. However, in the human there is negative staining for both a keratin cytoskeleton antigen and a cell surface antigen in the limbal epithelial zone. Efforts positively to identify human limbal stem cells continue, as do efforts to culture and transplant such cells.

Animals↗
PubMed1989

Concept and application of limbal stem cells.

Cumulative reported evidence indicates that some fraction of limbal basal epithelial cells are the stem cells for corneal epithelial cell proliferation and differentiation. Limbal epithelium is therefore crucial in maintaining the cell mass of corneal epithelium under normal conditions and plays an important role in corneal epithelial wound healing. Deficiency or absence of limbal stem cells explains well the pathogenesis of several ocular surface disorders characterised by defective conjunctival transdifferentiation or conjunctivalisation of cornea. This paper reviews and updates the basic concept of stem cells, the reported findings of limbal stem cells for corneal epithelium, and their therapeutic applications. Through this review, one hopes to gain a more complete understanding and increase proficiency in treating these diseases.

Animals↗
PubMed1999

Cell biology of posterior capsular opacification.

Posterior capsular opacification (PCO), a major complication of modern cataract surgery, necessitates further surgical intervention in 10-50% of patients. PCO results from the growth and transdifferentiation of lens epithelial cells left on the anterior capsule at the time of cataract surgery. These cells proliferate to form monolayers on the capsular surfaces, and such monolayers continue to line the anterior capsule leaflet many years after surgery. Some cells, however, differentiate or undergo a transition to another cell type, and these processes greatly contribute to PCO. Equatorial differentiation of cells to fibre-like structures leads to Soemmerring's ring formation and peripheral thickening of the capsular bag. Closer to the rhexis, cell swelling can result in globular Elschnig's pearls, which may occlude the visual axis. Cells at the rhexis edge and those in the space around the optic appear to undergo epithelial-mesenchymal transition. The resulting cells are fibroblastic in morphology, express the smooth muscle isoform of actin and secrete extracellular matrix containing proteins not normally present in the lens.

Animals↗
PubMed2004

Dominant-negative soluble PDGF-beta receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis.

Hepatic fibrogenesis is a consequence of hepatic stellate cells that become activated and transdifferentiate into a myofibroblastic phenotype with the ability to proliferate and synthesize large quantities of extracellular matrix components. In this process, platelet-derived growth factor (PDGF) is the most potent stimulus for hepatic stellate cell proliferation and migration, and is overexpressed during active hepatic fibrogenesis. This cytokine binds to the PDGF receptor type beta, activates Ras and sequentially propagates the stimulatory signal sequentially via phosphorylation of Raf-1, MEK and the extracellular-signal regulated kinases ERK1/ERK2. Hepatic injury is associated with both increased autocrine PDGF signaling and upregulation of PDGF receptor. In this study, we report that a dominant-negative soluble PDGF-beta receptor consisting of a chimeric IgG containing the extracellular portion of the PDGF receptor type beta blocks HSC activation and attenuates fibrogenesis induced by ligation of the common bile duct in rats. In culture-activated hepatic stellate cells, the soluble receptor blocks phosphorylation of endogenous PDGF receptor, phosphorylation of the ERK1/EKR2 signal and reduces proliferative activities of HSC. In vivo, both the delivery of the purified soluble PDGF antagonist and the administration of adenoviruses expressing the artificial transgene were able to reduce significantly the expression of collagen and alpha-smooth muscle actin. Our results demonstrate that PDGF plays a critical role in the progression and initiation of experimental liver fibrogenesis, and suggest that early anti-PDGF intervention should have a therapeutical impact on the treatment of liver fibrogenesis.

Adenoviridae↗
PubMed2005

EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade.

Human postnatal pancreatic duct cells are a potential source of new beta cells. Factors regulating proliferation of human pancreatic duct cells in vitro are unknown. In several other cell types, this process is influenced by ligands of the ErbB receptor family. The expression and functionality of the ErbB family members and their possible role in duct cell proliferation were determined. In cultured adult human pancreatic duct cells the different members of the ErbB family (ErbB1-4) were present at transcript and protein level. Stimulation of the duct cells with epidermal growth factor (EGF) and betacellulin results in Tyr-phosphorylation of ErbB1 and ErbB2, followed by activation of Shc, MEK1/2 and ERK1/2. Duct cells with activated ErbB signaling changed morphology and motility. EGF induced proliferation of a fraction of the duct cells and treatment with PD98059 prevented Ki67 expression in EGF-supplemented cells. When transduced with recombinant adenovirus expressing constitutively activated MEK1, duct cells proliferate and spread even in the absence of EGF. Importantly, the adult human duct cells retain their capacity to recapitulate ngn3-induced embryonic (neuro)endocrine differentiation after proliferation. Therefore, the present data support a possible role for human adult pancreatic duct cells, following expansion and transdifferentiation, as a source of insulin by transplantation to type I diabetes patients.

Adolescent↗