Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cellular Microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMedDate not supplied

Molecular biological ontogenesis of the thymic reticulo-epithelial cell network during the organization of the cellular microenvironment.

The thymus provides an optimal humoral microenvironment for the development of immunocompetent T cells. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The majority of RE cells have a round or irregular pale nucleus, which contains few, scattered, chromatin granules with a defined, spherical nucleolus, rich in basic histones. Their cytoplasm occasionally displays RNP granules, and is rich in non-histone proteins, fine phospholipid, lipid or cholesterin granules, and vacuoles filled with secreted substances. The cells of the subcapsular, endocrine RE cell layer (giant or nurse cells), characterized by PAS positive granules, express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to medullar RE cells, these subcapsular nurse cells also produce thymosins beta 3 beta 4. Thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA-DR) molecule restriction. These cells also contain transforming growth factor-beta (TGF-beta) type II receptors and participate in the positive selection of T cells. Transmission electron-microscopic (TEM) observations have defined four functional subtypes of medullar RE cells: undifferentiated, squamous, villous, and cystic. All subtypes are connected by desmosomes. Immunocytochemical observations have shown that the secreted thymic hormones, thymosin alpha 1 and thymopoietin (and its short form, thymopentin or TP5), are produced by the same RE cells. Thymic RE cells also produce numerous cytokines including IL1, IL6, G-CSF, M-CSF, and GM-CSF that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion, such as growth hormone, prolactin, adrenocorticotropic hormone, thyroid stimulating hormone, triiodothyronine, somatostatin, oxytocin, follicle stimulating hormone, luteinizing hormone, arginine vasopressin, growth hormone releasing hormone, corticotropin releasing hormone, nerve growth factor, vasoactive intestinal peptide, (pro) enkephalin, and beta-endorphin, production of a number of interleukins and growth factors, as well as the expression of receptors for all, by the same RE cell is an unique molecular biological phenomenon. These data illustrate the immensely important and diverse immuno-neuroendocrine functions of the thymic RE cellular network. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cell network represents an extremely important cellular and humoral microenvironment in homeopathic regulatory mechanisms of the multicellular organism. Intrathymic T lymphocyte selection is a complex, multistep process, influenced by several functionally specialized RE cell subtypes and under constant immuno-neuroendocrine regulation, reflecting the dynamic changes of the organism.

Animals↗
PubMed1978

Cellular microenvironment in relation to local blood flow.

The investigation was designed to identify microenvironmental factors that might be important in the regulation of local blood flow. Cellular microenvironment in terms of Po2, pH, [K+], [Cl-], [Ca2+] and lactate was measured in rat brain by means of specific microelectrodes. Vascular endothelium was stained in vivo with Thioflavine S. Local blood flow was measured with micro hydrogen electrodes. Some intracellular measurements of pH were made in conjunction with extracellular measurements. The main findings were that local autoregulation responses and blood flow changes in response to imposed hypoxic changes were very rapid (1-1.5 s). Microflow responses to changes in local cell activity were limited to a region not more than 250 micron in diameter. Increased blood flow in acute hypoxia occurred within 1-2 s of the fall in tissue Po2 and was much more rapid than changes in either pH or potassium. Intracellular pH changed within 10 s of the onset of severe hypoxia but in all cases the blood flow followed the Po2 much more closely than any other parameter. It is suggested that changes in capillary endothelium and local membrane transmission may play a part in autoregulatory mechanisms.

Animals↗
PubMedDate not supplied

Restoration of the thymic cellular microenvironment following autologous bone marrow transplantation.

Mammalian thymic histogenesis can be morphologically divided into three consecutive stages: 1) epithelial; 2) lymphopoietic or lympho-epithelial; and 3) differentiated cellular microenvironmental, with formation of Hassall's bodies (HBs). The marked reduction of the thymic cellular microenvironment (TCM) is a well-controlled physiological process and is presumably under both local and global regulation by the cells of the RE meshwork and by the neuroendocrine axis, respectively. In humans, the age-related decline of facteur thymique sérique (FTS) levels in blood begins after 20 years of age and FTS completely disappears between the 5th and 6th decade of life. In contrast, serum levels of thymosin-alpha 1 and thymopoietin seem to decline earlier, starting as early as 10 years of age. The influences of other hormones on the thymic involution have also been characterized: testosterone, estrogen and hydrocortisone treatment results in marked involution, cortisone and progesterone administration causes slight to moderate, while use of desoxycorticosterone has no effect. Since the thymus is the primary T-lymphopoietic organ during mammalian ontogenesis, its age-related involution with the typical immunomorphological alterations can be held responsible only for a decline in antigen-specific T-lymphocyte immune functions. Thymic involution and diminished T-lymphocyte proliferation can be partially restored by thymic tissue transplantation or administration of thymic hormones. The stimulus for thymic cell proliferation and differentiation is genetically determined within the organ implant. The only partial reconstitution of CD4+ T-helper-lymphocyte subset after anti-neoplastic chemotherapy and autologous BTM represents a significant, therapy-complicating, clinical problem. After high-dose chemotherapy, the restoration of thymus-dependent CD4+ T-lymphocyte genesis was reported only in children. Our radiation, stem cell transplantation, and hormone treatment experiments in animals resulted in age- and time-dependent regeneration of the cytoarchitecture of the TCM, as well as intrathymic lymphopoiesis.

Biopsy, Needle↗
PubMed1993

Avian macrophages: contribution to cellular microenvironment and changes in effector functions following activation.

The capacity of macrophages to generate metabolites and monokines having effector and regulatory functions can result in a major impact on their cellular microenvironment. Macrophage products synthesized in response to bacterial lipopolysaccharide stimulation include reactive oxygen and nitrogen intermediates as well as tumor necrosis factor (TNF). These secreted products of macrophages exhibit bioactivity either locally or systemically. Although the mechanism of action of avian monokines such as TNF-like factor may be similar to their mammalian counterparts, chicken TNF seems to lyse cells of chicken origin and not of mammalian origin. Furthermore, the generation and activity of products such as TNF is directly influenced by environmental stressors such as heat and toxins.

Animals↗
PubMedDate not supplied

Identification of neural crest derived cells within the cellular microenvironment of the human thymus employing a library of monoclonal antibodies raised against neuronal tissues.

The organization of optimal microenvironmental conditions within the developing thymus for lymphatic stem cell migration and their further maturation requires cellular and humoral participation of the neural crest. Recently, the immunophenotypical (IP) heterogeneity of lymphatic cells has become a scientific fact. Monoclonal antibodies (MoABs) produced against the various subpopulations of the reticulo-epithelial cells (RE) demonstrated their heterogeneity. We suggest that with a library of MoABs, raised against normal neuronal tissues, neural tumors, and a medulloblastoma cell line, including UJ13/A, UJ127.11, UJ167.11, UJ223.8, UJ308, J1153, A2B5, 215.D11, 275.G7, 282.1, antineurofilament (NF - med. m.w.), and anti-Thy-1 it is possible to recognize cells of neural crest origin within the postnatal thymic cellular microenvironment. Evidence has been collected concerning such connections between the nervous system and the thymus, such as the production of neuropeptides, oxytocin, and neurophysin by the thymus. Our immunohistochemical study was carried out on quick-frozen sections of human postnatal thymuses removed during open heart surgery, employing an indirect, alkaline phosphatase conjugated streptavidin-biotin technique. The employed MoABs reacted with the subcapsular (outer cortex) thymic nurse cells (TNCs) and with medullary RE cells, in close contact with already mature, immunocompetent T lymphocytes ready to leave the thymic microenvironment and enter the peripheral blood. The thymic medulla's strong immunoreactivity with A2B5, which binds to the GQ ganglioside, is typical for peptide secreting cells often migrated from the neural crest. A2B5+, Thy-1+ IP was demonstrated on the large TNCs. Cortical RE cells showed reactivity with UJ127.11, UJ223.8, and UJ308. Dense expression of neural crest antigens was detected in the Hassall's bodies (HBs) employing MoABs UJ223.8, UJ308, 215.D11, and 275.G7. These results suggest a neural crest origin for TNCs and for 20% to 30% of the cells of thymic microenvironment. The outer (peripheral) part of the HBs contained functionally very active RE cells. These RE cells also expressed antigens characteristic of the neural crest, detectable with MoABs UJ127.11, UJ223.8, UJ308, J1153, 215.D11, 275.G7 and A2B5.

Animals↗
PubMed1986

Generation of stable cellular phenotypes in a human malignant cell line conditioned by alterations in the cellular microenvironment.

Microenvironmental conditions may result in phenotypic changes of malignant cells and/or selection of preexisting variants with a growth advantage under the new growth conditions. The present study was initiated to evaluate the stability of changes in crucial cellular attributes as induced in vivo by nonimmunological mechanisms. Expression of major histocompatibility antigens, membrane immunoglobulin, in vitro growth rate, chromosome complement, and modal chromosome number were thus examined in a human B-lymphoma line (RH-L4) prior to and after short-term passage through the peritoneal cavity or spleen of newborn mice. Seven sublines (four from spleen and three from peritoneal cavity) of RH-L4 cells were established after the passage. These lines were found to differ phenotypically from the original line in respect to several or all of the attributes that were studied. These differences were stable for greater than 100 cell generations. Analyses of major histocompatibility complex Class II antigen expression indicated that the modulation of this antigen was independent of the immunological competence of the mice and unrelated to cell cycle-dependent variations. The emergence of the variant sublines seemed not to reflect a microenvironmentally determined selection of minority subpopulation in the original RH-L4 lymphoma line but, instead, induced by the growth conditions in the cellular microenvironment in the mouse. It is suggested that inductive processes may be of importance in the generation of phenotypic diversity within individual tumor cell populations, including the generation of phenotypic variants with high metastatic activity.

Animals↗
PubMed2003

The symmetry of initial divisions of human hematopoietic progenitors is altered only by the cellular microenvironment.

OBJECTIVE: We examined if cellular elements or adhesive ligands were able to alter asymmetric divisions of CD34(+)/CD38(-) cells in contrast to soluble factors at a single cell level. MATERIALS AND METHODS: After single cell deposition onto 96-well plates, cells were cocultured for 10 days with the stem cell supporting cell line AFT024, fibronectin (FN), or bovine serum albumin (BSA). The divisional history was monitored with time-lapse microscopy. Subsequent function for the most primitive cells was assessed using the myeloid-lymphoid-initiating cell (ML-IC) assay. Committed progenitors were measured using colony-forming cells (CFC). RESULTS: Only contact with AFT024 recruited significant numbers of CD34(+)/CD38(-) cells into cell cycle and increased asymmetric divisions. Although most ML-IC were still identified among cells that have divided fewer than 3 times, a significant number of ML-IC shifted into the fast-dividing fraction after exposure to AFT024. The increase in ML-IC frequency was predominantly due to recruitment of quiescent and slow-dividing cells from the starting population. Increase in CFC activity induced by AFT024 was found only among rapidly dividing cells. CONCLUSIONS: For the first time, we have demonstrated that asymmetric divisions can be altered upon exposure with a stem cell-supporting microenvironment. For the primitive subset of cells (ML-IC), this was predominantly due to recruitment into cell cycle and increased rounds of cycling without loss of function. Exposure to AFT024 cells also increased proliferation and asymmetric divisions of committed CFC. Hence direct communication between hematopoietic progenitors with stroma cells is required for maintaining self-renewal potential.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

[Histo-architectonic features of the autonomic nerve terminals and their cellular microenvironment in breast cancer tissues before and after radiotherapy].

The difference in the histoarchitectonics of structures of vegetative nervous terminals (VNT) before and after radiotherapy (RT) indicates the existence of VNT fragments sensitive and resistant to radiation damage. Heterogeneity of the local neuromediator background in tumor morphogenesis before and after RT can be clarified through studying the VNT cellular microenvironment.

Adolescent↗
PubMed1990

Chondrons from articular cartilage (II): Analysis of the glycosaminoglycans in the cellular microenvironment of isolated canine chondrons.

A chondron rich preparation was isolated from mature canine tibial cartilage using low-speed homogenization techniques. Proteoglycans were extracted from this preparation by exhaustive treatment with 4M guanidine-HCl. A significant proportion of the total proteoglycan, measured as uronic acid, was resistant to extraction and represented 27.9% in intact cartilage chips and 18.6% in the chondron fraction. Histochemical examination of chondrons confirmed that extraction resistant proteoglycans remained within the capsule of the chondron after 4M guanidine-HCl treatment. Electrophoretic analysis of the glycosaminoglycans extracted from intact cartilage chips and the chondron fraction showed approximately equivalent amounts of chondroitin sulphate (79.3%), keratan sulphate (16.3%) and hyaluronic acid (4.3%) present. In contrast, the extraction resistant residue in the chondron fraction was significantly enriched for hyaluronic acid (10.5%, p less than 0.05) but was depleted of chondroitin sulphate (70.9%, p less than 0.05). The major chondroitin sulphate isomer in the resistant fraction was chondroitin 6-sulphate while in the soluble fraction, the quantities of the two isomers were approximately equivalent. Comparison with previously published data suggests a role for minor collagens in the retention of proteoglycans in the cellular microenvironment.

Animals↗
PubMed2005

Hematopoietic progenitor cells and cellular microenvironment: behavioral and molecular changes upon interaction.

Cell-cell contact between stem cells and cellular determinants of the microenvironment plays an essential role in controlling cell division. Using human hematopoietic progenitor cells (CD34+/CD38-) and a stroma cell line (AFT024) as a model, we have studied the initial behavioral and molecular sequel of this interaction. Time-lapse microscopy showed that CD34+/CD38- cells actively migrated toward and sought contact with stroma cells and 30% of them adhered firmly to AFT024 stroma through the uropod. CD44 and CD34 are colocalized at the site of contact. Gene expression profiles of CD34+/CD38- cells upon cultivation with or without stroma for 16, 20, 48, or 72 hours were analyzed using our human genome cDNA microarray. Chk1, egr1, and cxcl2 were among the first genes upregulated within 16 hours. Genes with the highest upregulation throughout the time course included tubulin genes, ezrin, c1qr1, fos, pcna, mcm6, ung, and dnmt1, genes that play an essential role in reorganization of the cytoskeleton system, stabilization of DNA, and methylation patterns. Our results demonstrate directed migration of CD34+/CD38- cells toward AFT024 and adhesion through the uropod and that upon interaction with supportive stroma, reorganization of the cytoskeleton system, regulation of cell division, and maintenance of genetic stability represent the most essential steps.

Animals↗
PubMed1988

[Hematopoietic microenvironment: cellular and extracellular matrix elements].

In bone marrow, cellular stroma together with extracellular matrix (EM) provide an adequate microenvironment for the proliferation and differentiation of hemopoietic progenitor cells. In this article we describe studies on the cell characteristics of a main stromal phenotype, a fibroblast-like cell and its ability to produce in vitro EM components. Comparative studies were performed in fibroblast cultures derived from normal and acute lymphoblastic leukemic (ALL) bone marrow. The grow characteristics of fibroblasts from ALL marrow as well as its capacity to synthetize collagen, fibronectin and GAGs are impaired when compared to fibroblast from normal marrow. Thus, in ALL the impaired production of EM biomolecules by a transient damaged population of stromal cells, may contribute to the development of a defective microenvironment for hemopoiesis.

Bone Marrow Cells↗
PubMed1992

Follicular dendritic cells in the alternative antigen transport pathway: microenvironment, cellular events, age and retrovirus related alterations.

Follicular dendritic cells (FDC) are located in lymphoid follicles of secondary lymphoid tissues and play a pivotal role in the initiation and maintenance of the secondary antibody response. FDC are an integral part of the microenvironment of the follicle and function as members of the 'alternative antigen transport pathway.' This pathway consisting of the antigen transport cell-FDC-ICCOSOME-B cell axis, leads to the formation of germinal centers where antibody-forming cell and memory B cell development are initiated through interaction of FDC-retained antigen, B cells and T helper cells. Evidence suggests that these interactions are down-regulated through antibody feedback, or as needed, reactivated with the utilization of FDC-retained antigen for the maintenance of antibody levels. Age- and retrovirus-related FDC defects seriously compromise the capacity of this pathway to maintain immunity.

Aging↗
PubMedDate not supplied

Immunocytochemical detection of the homeobox B3, B4, and C6 gene products within the human thymic cellular microenvironment.

The homeobox (HOX) was originally described as a conserved DNA motif of about 180 base pairs. The protein domain encoded by the homeobox, the homeodomain, is thus about 60 amino acids long. The homeodomain is a DNA-binding domain, and many homeobox genes have now been shown to bind to DNA and regulate the transcription of other genes. Thus homeodomain proteins are basically transcription factors, most of which play a role in development. The homeobox genes seem to represent another class of oncofetal antigens involved in both normal development and carcinogenesis, as well as tumor progression. The expression pattern of three homeobox gene products (HOX-B3, HOX-B4, and HOX-C6) was examined immunocytochemically in human thymuses of different ages and developmental stages (prenatal: 16 weeks and postnatal: 3 years, 5 years, and 21 years) employing an indirect alkaline phosphatase conjugated antigen detection technique on formalin-fixed, paraffin-embedded tissue sections. The immunoreactivity was located in the thymic RE cellular network (cortical and medullar), showing different intensity (+3 to +4 or 50% to 90% and over 90% in the prenatal thymic tissue and +2 to +3 or 50% to 90% during the three different postnatal stages). Intense expression was identified in the thymic medulla, including very strong immunoreactivity in the immigrating, committed hematopoietic stem cells (HSCs) present within the interlobular connective tissue (ICT). Strong presence of the HOX-B3 and HOX-B4 proteins was detected in the thymic Hassall's bodies (HBs), suggesting an intensive functional activity of the RE cells present within these unique formations within the thymic medulla. The precise role of these and other HOX gene products in the various steps of intrathymic T lymphopoieis should be elucidated through further basic molecular biological research.

Adult↗
PubMed2004

Adenosine stimulation of proliferation of breast carcinoma cell lines: evaluation of the [3H]thymidine assay system and modulatory effects of the cellular microenvironment in vitro.

The purine nucleoside adenosine is produced at increased levels in the tissues of solid cancers as a result of local hypoxia. Adenosine inhibits the cell-mediated anti-tumor immune response, promotes tumor cell migration and angiogenesis, and stimulates the proliferation of tumor cells. We examined the stimulatory effect of adenosine on DNA synthesis, cell cycle progression, and cell proliferation in MCF7 and T-47D breast carcinoma cell lines in culture, and identified factors that modulate the growth response. The ability of adenosine to stimulate DNA synthesis, as measured by the incorporation of [(3)H]thymidine, was independent of the total radioactivity of the [(3)H]thymidine up to 10 microCi/ml, total thymidine concentrations up to 100 microM, and the labeling interval. It was also not affected by the presence of low-molecular-weight compounds (such as thymidine and adenosine) in the serum used to supplement the medium. Adenosine stimulated DNA synthesis and cell proliferation with an EC(50) of 4-6 microM and a maximum response at 30-100 microM, when given as a single addition. The stimulatory effect of adenosine involved progression through the cell cycle and a genuine increase in cell number, in the absence of significant apoptotic or necrotic cell death. The mitogenic effect of adenosine was dependent upon the culture cell density, with an optimum adenosine response at around 50% of confluent density. The response was also highly dependent upon the form of the serum addition to the growth medium, with the best response elicited in the presence of low concentrations of nonfetal bovine serum, although adenosine was mitogenic under standard culture conditions. The effects of serum supplementation and cell density were not due to differences in the rate of adenosine metabolism by either serum or cellular enzymes, but appeared to result from changes in the sensitivity to adenosine of the cell population in response to environmental cues. We, therefore, find that adenosine is consistently mitogenic for human breast carcinoma cells, and that the [(3)H]thymidine incorporation assay is a valid measure of this response. The data are consistent with the stimulatory effect of adenosine on cell proliferation being modulated by the local cellular environment.

Adenosine↗
PubMed1987

Immunoregulation in the Peyer's patch microenvironment. Cellular basis for the enhanced responses by the B cells of X-linked immunodeficient CBA/N mice.

The Peyer's patches (PP) of X-linked immunodeficient (xid) CBA/N and hemizygous (CBA/N X DBA/2)F1 (CDF1) male mice contain a B cell subpopulation that expresses the Lyb-5 maturational marker and is responsive to type 2 and T cell-dependent antigens in vitro, a B cell phenotype which is absent from the spleens of xid mice. Experiments reported here show that xid spleen B cells co-cultured with B cell-depleted PP cells from xid mice differentiated into specific plaque-forming cells in response to trinitrophenyl-Ficoll (type 2) and sheep erythrocytes (T cell-dependent). Two cell types were involved in this normalization of xid B cell responses. An accessory cell activity present in the PP, but not the spleens, of both CDF1 male (xid) and CDF1 female (normal) mice was required for the response to either the type 2 or T cell-dependent antigens. In the presence of this PP accessory cell, T cells from the PP of either xid or normal mice supported responses to both classes of antigens. In contrast, T cells from the spleens of xid mice did not support the response to trinitrophenyl-Ficoll, although the splenic T cells from normal mice did synergize with PP accessory cells in allowing plaque-forming cell development by xid B cells to this type 2 antigen. The xid PP T cell activity required for the type 2 response by xid B cells was present in the Ly-1+, Lyt-2- subpopulation, and the xid PP accessory cell activity was provided by an enriched population of dendritic accessory cells. These results demonstrate the the lymphoreticular cells comprising the PP microenvironment provide effective support for the differentiation of xid B cells in response to type 2 and T cell-dependent antigens.

Animals↗
PubMed1991

Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage.

Chondrons were isolated from human and canine osteoarthritic cartilage using low-speed homogenization techniques. Changes in chondron morphology were evaluated using differential interference-contrast microscopy, phase-contrast microscopy, and histochemical and ultrastructural methods. Chondrocyte viability was assessed using fluorescein diacetate staining, and chondron metabolism was investigated using autoradiography. The results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters. These techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis.

Aged↗
PubMed2001

Telomerase deregulation in immortalized human epidermal cells: modulation by cellular microenvironment.

Modulation of telomerase activity was investigated in the spontaneously immortalized SIK human epidermal cell line. Although these cells displayed low telomerase activity in early passage, similar to that in normal human epidermal cells, the activity was found to be markedly stimulated by cultivation in the presence of epidermal growth factor (EGF). This stimulation was evident in later passage as well, but the relative increase was not as marked inasmuch as the basal activity increased with passage. Normal human epidermal cells in culture displayed low telomerase activity shortly after inoculation and it decreased further with time, reaching minimum levels several days after cultures became confluent, independently of EGF addition. SIK cultures grown in the absence of EGF behaved similarly. However, addition of EGF to these cultures prevented the telomerase decrease otherwise observed in log-phase growth. In the presence of EGF, telomerase activity was maximal approximately 12 days after inoculation and then decreased considerably at confluence. In the absence of EGF, telomerase activity was increased by UV exposure despite its suppressive effect on keratinocyte growth. In the absence of EGF, the protein tyrosine phosphatase inhibitor vanadate stimulated growth marginally and did not have a pronounced effect on telomerase. In the presence of EGF, however, vanadate antagonized EGF action on cell growth and on telomerase activity, and it stimulated spontaneous envelope formation in a dose-dependent manner. Thus the spontaneously immortalized SIK line provides a useful model for study of telomerase modulation during the neoplastic progression of keratinocytes.

3T3 Cells↗
PubMed2002

Engineering cellular microenvironments to improve cell-based drug testing.

Recent progress in the biology of cell adhesion is enabling cell culture models to better reproduce in vivo functions. Cues from adhesion to extracellular matrix and neighboring cells are important regulators of cell behaviors. The recent adaptation of semiconductor tools to spatially organize cells and their adhesions has enhanced our ability to engineer cell functions ex vivo. By using these tools to create more in vivo-like cultures, cell-based drug discovery and target validation could be improved. This review explores the biological advances made by these microfabrication tools and discusses how they could enable high-throughput cell-based assays.

Animals↗