Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction.

Aims: Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis.

Calcineurin in the heart: New horizons for an old friend.

Calcineurin, also known as PP2B or PPP3, is a member of the PPP family of protein phosphatases that also includes PP1 and PP2A. Together these three phosphatases carryout the majority of dephosphorylation events in the heart. Calcineurin is distinct in that it is activated by the binding of calcium/calmodulin (Ca/CaM) and therefore acts as a node for integrating Ca signals with changes in phosphorylation, two fundamental intracellular signaling cascades.

Single-cell characterization and metabolic profiling of in vitro cultured human skeletal progenitors with enhanced in vivo bone forming capacity.

Cell populations and their interplay provide the basis of a cell-based regenerative construct. Serum-free preconditioning can overcome the less predictable behavior of serum expanded progenitor cells, but the underlying mechanism and how this is reflected in vivo remains unknown. Herein, the cellular and molecular changes associated with a cellular phenotype shift induced by serum-free preconditioning of human periosteum-derived cells were investigated.

Novel Autoimmune IgM Antibody Attenuates Atherosclerosis in IgM Deficient Low-Fat Diet-Fed, but Not Western Diet-Fed Mice.

Objective: Oxidized phospholipids (OxPL), such as the oxidized derivatives of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine, and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine, have been shown to be the principal biologically active components of minimally oxidized LDL (low-density lipoprotein). The role of OxPL in cardiovascular diseases is well recognized, including activation of inflammation within vascular cells. Atherosclerotic mice fed a high-fat diet develop antibodies to OxPL, and hybridoma B-cell lines producing natural anti-OxPL autoantibodies have been successfully generated and characterized.

Aberrant Wnt Signaling Pathway in the Hematopoietic Stem/Progenitor Compartment in Experimental Leukemic Animal.

The evolutionarily conserved Wnt signaling pathway regulates physiological hematopoiesis, a process of formation of blood cells and has been shown to play crucial role in the development of both myeloid and lymphoid malignancies. The Wnt signaling pathway can be broadly divided into canonical and non-canonical pathways. In the present study, we investigated the pathobiology of leukemia by studying the expression profile of Wnt proteins, receptors, key signaling intermediates and endogenous Wnt antagonist involved in canonical and non-canonical pathways in the bone marrow (BM) hematopoietic stem/progenitor cell (HSPC) compartment of experimental leukemic mice.

Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells.

Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2). Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation.

Differential expression of mitotic regulators and tumor microenvironment influences the regional growth pattern of solid sarcoma along the cranio-caudal axis.

Soft tissue sarcomas are relatively rare, unusual, anatomically diverse group of malignancies. According to the recent literature and medical bulletins, tumor growth and aggressiveness immensely relies on its anatomical locations. However, it is unclear whether the cranio-caudal anatomical axis of the mammalian body can influence sarcoma development and the underlying molecular mechanisms are not yet deciphered.

Adam10 mediates the choice between principal cells and intercalated cells in the kidney.

A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane-anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice.

Differential remodeling of cadherins and intermediate cytoskeletal filaments influence microenvironment of solid and ascitic sarcoma.

Different forms of sarcoma (solid or ascitic) often pose a critical medical situation for pediatric or adolescent group of patients. To date, predisposed genetic anomalies and related changes in protein expression are thought to be responsible for sarcoma development. However, in spite of genetic abnormality, role of tumor microenvironment is also indispensable for the evolving neoplasm.

Phenotypic alteration of limbal niche-associated limbal epithelial stem cell deficiency by ultraviolet-B exposure-induced phototoxicity in mice.

Good vision requires a healthy cornea, and a healthy cornea needs healthy stem cells. Limbal epithelial stem cells (LESCs) are a traditional source of corneal epithelial cells and are recruited for the continuous production of epithelium without seizing throughout an animal's life, which maintains corneal transparency. Like the maintenance of other adult somatic stem cells, the maintenance of LESCs depends on the specific microenvironmental niche in which they reside.

Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model.

The mechanistic interplay between pesticide exposure and development of marrow aplasia is not yet well established but there are indices that chronic pesticide exposure in some instances causes marrow aplasia like haematopoietic degenerative condition in human beings. Canonical Hedgehog (Hh) signalling has multiple roles in a wide range of developmental processes, including haematopoiesis. The present study was designed to explore the status of four important components of the canonical Hedgehog signalling cascade, the Sonic Hedgehog (Shh), Ptch1, Smo, and Gli1, in a mouse model of chronic pesticide-induced bone marrow aplasia.

Pesticide induced marrow toxicity and effects on marrow cell population and on hematopoietic stroma.

Long term inhalation of toxic pesticides used for the domestic and industrial purposes have been shown to cause moderate to severe hematotoxicity and increased incidence of several marrow degenerative diseases, specifically hypoplastic bone marrow failure condition in humans. The progression of pesticide induced hematotoxicity and the exact underlying mechanisms of toxicity that play major role in limiting normal hematopoiesis are not quite well explained. In this present study, we have developed an animal model of hypoplastic bone marrow failure following pesticide exposure to show the deleterious effects of toxic pesticides on mouse hematopoietic system.

Pesticide induced alterations in marrow physiology and depletion of stem and stromal progenitor population: an experimental model to study the toxic effects of pesticide.

Long-term exposure of agriculturally used organochloride and organophosphate pesticides have been shown to cause long-lasting hematotoxicity and increased incidence of aplastic anemia in humans. The mechanisms involved in pesticide induced hematotoxicity and the features of toxicity that may play a major role in bone marrow suppression are not known. The aim of the present study was to investigate the hematological consequences of pesticide exposure in swiss albino mice exposed to aqueous mixture of common agriculturally used pesticides for 6 h/day, 5 days/week for 13 weeks.

Leukemic stromal hematopoietic microenvironment negatively regulates the normal hematopoiesis in mouse model of leukemia.

Background And Objective: Leukemic microenvironment has a major role in the progression of leukemia. Leukemic cells can induce reversible changes in microenvironmental components, especially the stromal function which results in improved growth conditions for maintaining the malignant leukemic cells. This study aimed to investigate the survival advantage of leukemic cells over normal hematopoietic cells in stromal microenvironment in long term.

Alteration in marrow stromal microenvironment and apoptosis mechanisms involved in aplastic anemia: an animal model to study the possible disease pathology.

Aplastic anemia (AA) is a heterogeneous disorder of bone marrow failure syndrome. Suggested mechanisms include a primary stem cell deficiency or defect, a secondary stem cell defect due to abnormal regulation between cell death and differentiation, or a deficient microenvironment. In this study, we have tried to investigate the alterations in hematopoietic microenvironment and underlying mechanisms involved in such alterations in an animal model of drug induced AA.

Primitive Sca-1 Positive Bone Marrow HSC in Mouse Model of Aplastic Anemia: A Comparative Study through Flowcytometric Analysis and Scanning Electron Microscopy.

Self-renewing Hematopoietic Stem Cells (HSCs) are responsible for reconstitution of all blood cell lineages. Sca-1 is the "stem cell antigen" marker used to identify the primitive murine HSC population, the expression of which decreases upon differentiation to other mature cell types. Sca-1(+) HSCs maintain the bone marrow stem cell pool throughout the life.

Sca-1 / c-Kit receptor expression and apoptosis pattern in ENU induced MDS mice.

The bone marrow is the major site of haemopoiesis in adult human. It contains cells that represent the stages in the development of different types of blood cells e.g.

Phenotypic alteration of bone marrow HSC and microenvironmental association in experimentally induced leukemia.

Leukemia is a heterogeneous disorder of bone marrow (BM) failure syndrome where normal hematopoiesis gets altered due to transformation of either the normal hematopoietic cell or the hematopoietic microenvironment or both. Scientists have tried for decades to understand leukemia development in the context of therapeutic strategies. The existence of "leukemic stem cells" and their possible role in leukemogenesis have only recently been identified and it has changed the perspective with regard to new approaches for treating the disease.

An animal model of chronic aplastic bone marrow failure following pesticide exposure in mice.

The wide use of pesticides for agriculture, domestic and industrial purposes and evaluation of their subsequent effect is of major concern for public health. Human exposure to these contaminants especially bone marrow with its rapidly renewing cell population is one of the most sensitive tissues to these toxic agents represents a risk for the immune system leading to the onset of different pathologies. In this experimental protocol we have developed a mouse model of pesticide(s) induced hypoplastic/aplastic marrow failure to study quantitative changes in the bone marrow hematopoietic stem cell (BMHSC) population through flowcytometric analysis, defects in the stromal microenvironment through short term adherent cell colony (STACC) forming assay and immune functional capacity of the bone marrow derived cells through cell mediated immune (CMI) parameter study.

Effects of inorganic arsenic on bone marrow hematopoietic cells: an emphasis on apoptosis and Sca-1/c-Kit positive population.

Apoptosis, proliferation and differentiation are balanced molecular processes which may alter their pattern during environmental insults. Arsenic is an environmental pollutant, ranks 20(th) in abundance in the earth crust, 14(th) in sea water and 12(th) in the human body. Millions of people worldwide are chronically exposed to arsenic often due to naturally occurring arsenic in ground water.

Sca-1 expression pattern in the mouse limbal epithelium and its association with cell cycle.

Stem Cell Antigen-1 or Sca-1 is a cell surface receptor protein commonly used to detect adult murine haematopoietic stem cell population. Outside the haematopoietic system Sca-1 is similarly expressed in stem and progenitor cells in a wide variety of tissues and organs such as skeletal muscle, mammary gland, prostate, heart, liver and dermis. Thus Sca-1 has become a candidate marker in the search of tissue specific stem cells.

The bone marrow stem stromal imbalance--a key feature of disease progression in case of myelodysplastic mouse model.

Myelodysplastic syndromes (MDSs) represent a spectrum of disorders that are generally thought to arise from a defective hematopoietic stem cell leading to clonal, dysregulated hematopoiesis. Although it is generally agreed that the marrow microenvironment plays a role in the biology of MDS, it is unclear whether this represents an intrinsically abnormal stromal compartment derived from the MDS clone. Hematopoiesis requires cooperation between progenitors and a variety of functionally and phenotypically different cell types that form the bone marrow stroma.

Kinetic impairment of haemopoietic stem cells in experimentally induced leukemia and aplastic anemia: an inverse correlation.

The production of blood cells from bone marrow (BM) hematopoietic stem cells (HSC) is regulated by a number of cytokines and growth factors that influence cell survival; differentiation, proliferation and apoptosis in health and supposedly, such mechanisms are deregulated in diseased conditions. As far as cellular kinetics is concerned HSCs are relatively quiescent in adults, have the ability to replicate symmetrically and asymmetrically and predictably exhibit multi-lineage hematopoietic reconstitution potential. HSC drive hematopoiesis and homeostasis by contracting and expanding the pool of hematopoietic cells in the bone marrow.