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Results for “Cellular Microenvironment”

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At least 91 records · Page 5Linked to original sources
PubMed1993

Cellular interactions in hemopoietic progenitor cell homing: a review.

Within the bone marrow microenvironment, dynamic cellular interactions are constantly occurring. These interactions involve hemopoietic stem cells, progenitor cells and maturing cells, physically interacting with other cells, some of which may function as accessory cells, and others which comprise the stromal elements; hemopoietic cells also interact with non-cellular elements, such as glycoproteins and fibrous proteins of the extracellular matrix (ECM). These interactions serve to regulate normal hemopoiesis by allowing the communication of regulatory information, migration and subsequent homing of stem cells within specific organs, and presentation of hemopoietic growth factors in a biologically relevant fashion. The goal of this review is to examine the specific cellular interactions that relate to the phenomenon of homing of intravenously transplanted stem cells to the bone marrow.

Amino Acid Sequence↗
PubMed1989

Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review.

The objective of this review article is to summarize current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies. A compilation of available data from the literature on blood flow, oxygen and nutrient supply, and tissue oxygen and pH distribution in human tumors is presented. Whenever possible, data obtained for human tumors are compared with the respective parameters in normal tissues, isotransplanted or spontaneous rodent tumors, and xenografted human tumors. Although data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. As a result, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation and with a hostile metabolic microenvironment (e.g., existence of severe tissue acidosis). Significant variations in these relevant parameters must be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Furthermore, this synopsis will attempt to identify relevant pathophysiological parameters and other related areas future research of which might be most beneficial for designing individually tailored treatment protocols with the goal of predicting the acute and/or long-term response of tumors to therapy.

Adenosine Triphosphate↗
PubMed1990

Sugar receptors of the stromal cell layer in human long-term bone marrow cultures: their presence, modulatory responses to changes in the microenvironment and potential role in cellular adhesion.

Intimate cellular contacts and coordinated supply of regulatory factors are required to maintain the still inexplicable dynamic equilibrium of hemopoiesis. To infer the potential participation of protein-carbohydrate interaction in this complex process, human long-term bone marrow cultures were initiated from eleven donors, and the adherent cell layer was characterized enzyme- and immunohistochemically. Utilizing an array of carrier-immobilized carbohydrate ligands and sulfated polysaccharides as probes, specific binding of various constituents of the carbohydrate chains of cellular glycoconjugates to the stromal cells was unmistakably disclosed. Biochemical analysis, employing glycocytologically effective ligands in affinity chromatography, corroborated this result. The extent of binding was markedly lower in the two samples, derived from leukemia patients. Pronounced adaptive responses for this characteristic followed changes in the culture microenvironment that are known to influence qualitative and quantitative aspects of hemopoiesis in vitro, namely omission of hydrocortisone and horse serum or addition of cytokines. Similarly, such adaptive modulation occurred on the level of accessible cell surface receptors, monitored by neoglycoenzymes. These binding sites can be involved in mediation of cellular interactions, as revealed in a model system by the interference of N-acetyl-D-galactosamine in cell adhesion. Overall, the results support the idea that glycobiological recognition may contribute to the functional integrity of the stromal cell layer as well as provide the basis for further analysis.

Bone Marrow↗
PubMed2026

Spatial Proteomics of the Human Atherosclerotic Microenvironment Reveals Heterogeneity in Intraplaque Proteomes and Extracellular Matrix Remodeling.

Plaque heterogeneity underlies the propensity of atherosclerotic lesions to rupture and trigger cardiovascular events. Most proteomic studies examine bulk changes, obscuring key spatial differences in protein abundance. We report a high-resolution spatial proteomics workflow exploring the molecular landscape of human plaques and a murine myocardium. By combining laser capture microdissection with high-sensitivity ion-mobility mass spectrometry, spatial profiling of cellular and extracellular matrix (ECM) proteomes was achieved. Over 2700 proteins were detected from 50,000 μm2 areas, revealing substantial intraplaque heterogeneity across distinct regions (lipid-rich, media, shoulder, necrotic core, intima) and distance from the artery lumen. Inverse correlations between proteases (cathepsin B) and core structural ECM proteins (perlecan, HSPG2) indicated active ECM remodeling. Analysis of media layers indicated distinct protein signatures associated with smooth muscle contraction and cell-cell communication. Blood coagulation signatures, including platelet degranulation and fibrin formation, were enriched at the intima. Inflammatory (clusters of differentiation 4/68, CD4/CD68; vascular cell adhesion molecule 1, VCAM1) and vascular damage markers (tenascin-C, TNC) were enriched in shoulder regions. The necrotic core was dominated by blood proteins, consistent with intraplaque hemorrhage. This workflow resolves proteomic changes over ∼200 μm distances, providing unprecedented insights into plaque morphology and offers a powerful tool for elucidating plaque biology.

Humans↗
PubMed2026

Mapping subcellular microenvironments using oligonucleotide-directed proximity labeling.

Understanding how cells compartmentalize their biomolecules into discrete structures remains one of the fundamental goals of cell biology. The proliferation of proximity labeling (PL) technologies has been invaluable toward this goal, enabling biochemical "dissection" of compartments that would be intractable to classical biochemical methods. While robust PL approaches have long been established for targeting proteins of interest, targeting nucleic acids-RNAs and genomic loci-has remained significantly more challenging. Here, we review recent advancements in the field that overcome this longstanding roadblock by using programmable DNA oligonucleotides to direct PL enzyme localization. These tools are already revealing new insights into the molecular architecture of cellular compartments that lie at the heart of gene expression. They also provide a foundation for developing a new generation of PL tools that exploit the modularity and programmability of oligonucleotide-based devices to enable precise spatiotemporal control at previously inaccessible targets and in challenging specimen types.

Oligonucleotides↗
PubMed1986

A new approach to the evolution of the blastic crisis from chronic myelocytic leukemia: dynamic interplay of cellular alterations and a changing microenvironment.

The mechanisms responsible for the massive hyperplasia and for the blastic crisis in chronic myelocytic leukemia are poorly understood. The most generally accepted hypothesis proposes that this progression is due to the development of genetic instability in the leukemic cells. In particular, the two phases of the disease are believed to reflect different, discrete genetic events. Such events remain undefined as yet, and the causal significance of observed genetic aberrations is not clear. An alternative hypothesis is presented here. It is assumed that the feedback interactions adjust the relative probabilities of maturation and replication of the 'committed' as well as the pluripotent cells, and further that mitotic cells at all stages possess considerable phenotypic adaptability; in particular their self-renewal capacity can vary in response to changes in the cellular composition of the tissue even within a conventionally defined compartment. On this basis, it is shown that chronic leukemia can arise and evolve into the blastic crisis from a progressive decline in a single clonal characteristic--inducibility to maturation. It is shown, with the help of mathematical considerations, how an initial hereditable event in an early hemopoietic cell can cause a disturbance of the tissue which feeds back onto the individual members of the clone, resulting in a cascade of dynamic changes which can lead to blast cell dominance.

Cell Cycle↗
PubMed2025

Discovery of a Linked Constellation of Gene Expression Revealed by Local Editing of Fibroblasts in Tumors.

Fibroblasts play critical roles in regulating cellular relationships during tissue homeostasis, immunity, and tumor biology at multiple sites. However, tools to perturb fibroblasts at just one site in vivo are limited, restricting our understanding of how these cellular relationships develop on a local level. We optimized local gene editing of fibroblasts in multiple mouse tumor models to investigate how locally restricted fibroblast perturbations affect the cellular tumor microenvironment (TME). By knocking out surface receptors Osmr, Tgfbr2, or Il1r1 on cancer-associated fibroblasts (CAFs), we uncover that TGFBR2 signaling loss uniquely induces the emergence of a Col18a1 hi CAF cell state that is distinct from previously described fibroblast states and is associated with worse survival in human PDAC patients. Further application of a local as well as combinatorial gene knockout technology in CAFs reveals a circuit in which these Col18a1 hi CAFs reshape the TME by recruiting Siglec-Fhi neutrophils via Cxcl5 expression; and that the Col18a1 hi CAF cell state is further dependent on TNFR1 and canonical Wnt signaling. Together, a fast, affordable, and modular engineering method is demonstrated, allowing discovery of a modified fibroblast identify, as well as the network details of a local inter-cellular circuitry in a tumor.

Journal Article↗
PubMed1990

Blood flow, oxygen consumption and tissue oxygenation of human tumors.

The objective of this article was to summarize current knowledge of blood flow and oxygen supply to human tumors, parameters which go hand in hand, and in turn critically determine the cellular metabolic microenvironment of human malignancies. A compilation of available data on blood flow, oxygen supply, and tissue oxygen distribution in human tumors is presented. Though data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. Comparable to rodent tumors, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation, and with a hostile metabolic microenvironment. Significant variations in these relevant parameters have to be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging.

Erythrocytes↗
PubMed1991

Arachidonic acid and diacylglycerol act synergistically to activate protein kinase C in vitro and in vivo.

Using a well-defined model membrane bilayer system, incorporation of both lipid second messengers, 1,2-diacylglycerol and arachidonic acid, at submaximal activating concentrations, resulted in a synergistic activation of protein kinase C in a Ca2+/phosphatidylserine-dependent manner as measured by monitoring phosphorylation of phosphoprotein substrates. The arachidonic acid appears to modulate membrane properties both at the hydrocarbon core and the membrane surface increasing the availability of the diacylglycerol which can bind to and subsequently activate the enzyme. Co-application of these two lipid activators to the Hermissenda photoreceptor reduced K+ channel conductance in a synergistic manner via a PKC-dependent pathway. Thus, these in vivo and in vitro studies suggest that the membrane bilayer properties of these PKC lipid activators interact to specifically regulate the cellular lipid microenvironment resulting in PKC activation.

Animals↗
PubMed1990

Oxygenation of human tumors.

The objective of this article is to summarize current knowledge of oxygen supply to human tumors and of tumor tissue oxygenation, parameters which go hand in hand, and in turn critically determine the cellular metabolic microenvironment of human malignancies. A compilation of available data on these factors is presented. Though data on human tumors in situ are scarce and there may be significant errors associated with the technique used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic oxygen supply to many tumor cells. Comparable to experimental rodent tumors, O2-depleted areas develop in many human malignancies which coincide with nutrient and energy deprivation, and with a hostile metabolic microenvironment. Significant variations in these relevant parameters have to be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Therefore, evaluation of the oxygenation status in individual tumors before therapy might be most beneficial for designing specifically tailored treatment protocols for individual subjects in order to improve tumor response to treatment.

Blood Flow Velocity↗
PubMed1987

[Influence of stromal cells on the development of allogeneic bone marrow grafts].

The development of long-term in vitro marrow culture techniques has allowed in vitro characterization of the cellular composition and functional attributes of the human bone marrow stromal microenvironment. Interest in these studies has increased because the interactions between hematopoiesis and the microenvironment through direct cellular contact or production of inhibiting or stimulating factors are better known. The role of the microenvironment in bone marrow transplantation needs further study. The main points of interest are: the role of the host microenvironment in sustaining engraftment, the influence of marrow manipulations on the microenvironment of the donor marrow inoculum, the role of the microenvironment on the establishment of complete chimerism and in the host-donor interactions.

Bone Marrow Cells↗
PubMed1978

Hematopoiesis on cellulose ester membranes (CEM). II. Enrichment of the hematopoietic microenvironment by the addition of selected cellular elements.

Cellulose ester membranes (CEM) were folded into a trilaminar open-ended tube which was implanted into the peritoneal cavity of mice. CEM rapidly acquired a stromal core with many features of marrow such as fat, fibroblasts, an abundant sinusoidal microcirculation and monocyte-macrophage-like cells. CEM took up 59iron, 99technetium sulfur colloid and produced CSF in in vitro culture but their microenvironment supported only granulopoiesis. CEM were coated on their interior surfaces with bone marrow or regenerating medullary cavity mesenchyme or bone but the stromal cores supported only granulopoiesis after 3 weeks to 3 months of implantation. CEM coated with spleen and implanted into mice developed trilineal hematopoiesis within 6 weeks with abundant erythropoiesis and megakaryocytopoiesis in addition to granulopoiesis. These CEM differed from splenic tissue in that only scattered lymphoid tissue was present. CEM coated with bone marrow and bone developed trilineal hematopoiesis but only after3--6 months of peritoneal implantation. CEM coated with regenerating medullary cavity mesenchyme failed to develop trilineal hematopoiesis. Cyclophosphamide injection did not enhance hematopoiesis. These experiments indicate that splenic, marrow and bone tissue contain stromal elements capable of being transferred onto CEM which then develop a microenvironment capable of supporting trilineal hematopoiesis.

Animals↗
PubMed1995

Confocal microscopy of cells implanted into tissue blocks: cell migration in long-term histocultures.

In three-dimensional tissues in vivo, cells find themselves in a unique, heterogeneous microenvironment among various cellular and noncellular elements. Cells are greatly affected by and contribute to their physical and chemical microenvironments. However, live cells are currently studied predominantly in homogeneous monolayer cultures where newly established contacts might be fundamentally different from contacts in vivo. Several systems have been suggested to simulate the three-dimensional environment of real tissue. In this report, we describe a new system for studying cell behavior inside real tissues in vitro. By fluorescently labeling mouse tumor cells, them implanting them into cultured tissue blocks (histocultures), we have observed cellular location and followed their locomotion, within tissues in vitro for days. We discuss the potential of the described system for studying different aspects of cell behavior in a nativelike microenvironment.

Animals↗
PubMed2026

The IL-1 system in inflammation and cancer.

Inflammation is a pathogenetic driver of several pathological conditions, including cancer. The tumor microenvironment, which includes cellular, molecular, and structural components, is an essential component of cancer, involved in tumor promoting or controlling processes. In particular, inflammatory players contribute to the establishment of a tumor-promoting microenvironment, which affects all stages of tumor development, from initiation to metastasis, as well as response to therapy. The IL-1 system includes two large sets of structurally related ligands and receptors, with agonist or regulatory activity, playing non-redundant roles in inflammation and immunity. Each of them has specific functions in tissue homeostasis, inflammation, innate and adaptive immune responses, and potentially contributes to processes related to carcinogenesis and metastasis, or immune-mediated control of cancer cells. Depending on the context and cellular target, IL-1 family members may play dual roles in cancer, driving both pro- or anti-tumor processes. IL-1α and IL-1β can directly promote cancer cell proliferation, survival, and plasticity, in addition to contribute to the establishment of a pro-inflammatory environment that promotes tissue remodeling, cellular stress responses, and genomic instability. On the other hand, IL-1 is a lymphoproliferative and activating molecule in innate and adaptive responses, thus contributing to anti-tumor immune mediated responses. In addition, members of the IL-1 system act as regulators of mechanisms involved in cancer, including emergency hematopoiesis, trained immunity, and metabolism. Here, we will provide an overview of the IL-1 system in cancer and discuss the functional complexity of IL-1 family cytokines, which orchestrate both protective and pro-tumorigenic responses, by directly acting on cancer cells and by driving environmental stimuli which indirectly act on cancer cells.

Humans↗
PubMed1987

A new in vivo model to study the influence of the microenvironment in the regeneration of the central nervous system.

In order to study the 'in vivo' regenerative capacity of the central nervous system, a semipermeable tube was placed in the axis of the lesioned nigrostriatal pathway of adult rats. In spite of a correct positioning of the tube, no growing central nervous processes were observed within the tube after 3 to 6 weeks when it was left empty. However, when the lumen of the tube was previously filled with a pre-degenerated sciatic nerve, unmyelinated and myelinated fibers were observed growing in the peripheral graft. Since the content of the tube can be modified, it appears that this model can be used to test the capability of cellular or acellular microenvironments to promote the 'in vivo' regeneration of the mammalian central nervous system fibers.

Animals↗
PubMed2026

Integrated single-cell and spatial transcriptomic analyses reveal malignant epithelial glycolytic heterogeneity and spatial niche remodeling during colorectal cancer progression.

Colorectal cancer (CRC) progression is shaped by metabolic reprogramming and complex interactions within the tumor microenvironment. However, the cellular heterogeneity, spatial organization, and clinical relevance of glycolytic activity in CRC remain incompletely understood. In this study, we integrated single-cell RNA sequencing, bulk transcriptomics, and spatial transcriptomics data to systematically characterize glycolytic heterogeneity in CRC. Glycolytic activity was quantified using five independent scoring methods, consistently showing that epithelial cells exhibited the highest glycolytic activity across the two single-cell cohorts. Stratification of CopyKAT-verified aneuploid malignant epithelial cells into high-glycolysis (HG) and low-glycolysis (LG) subgroups by glycolysis scores revealed that HG cells exhibited higher stemness scores and chromosomal copy number variations. Cell-cell communication analysis revealed that, compared with LG cells, HG cells exhibited increased interaction frequency and strength with immune and stromal populations, indicating enhanced malignant epithelial-microenvironment crosstalk. Spatial transcriptomics analyses further revealed that glycolytic activity varied across normal colorectal tissue, primary CRC, and colorectal liver metastases, accompanied by progressive remodeling of epithelial-associated spatial niches and MIF-mediated intercellular communication. Bulk transcriptomic analysis identified a glycolysis-related prognostic signature with robust predictive performance, which served as an independent prognostic factor for overall survival in CRC cohorts. Collectively, these findings indicate that glycolytic heterogeneity is a key feature of CRC malignant epithelial cells and is closely associated with tumor progression, microenvironmental remodeling, and clinical outcomes.

Humans↗