Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Spheroids, Cellular”

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 73 records · Page 4Linked to original sources
PubMed2000

Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture.

Oxygen consumption, glucose, lactate, and ATP concentrations, as well as glucose and lactate turnover rates, have been studied in a three-dimensional carcinogenesis model of differently transformed rat embryo fibroblasts (spontaneously immortalized Rat1 and myc-transfected M1, and the ras-transfected, tumorigenic descendants Rat1-T1 and MR1) to determine metabolic alterations that accompany tumorigenic conversion. Various bioluminescence techniques, thymidine labeling, measurement of PO(2) distributions with microelectrodes, and determination of cellular oxygen uptake rates (Qc(O(2))) have been applied. In the ras-transfected, tumorigenic spheroid types, the size dependencies of some of the measured parameters exhibited sharp breaks at diameters of approximately 830 microm for Rat1-T1 and approximately 970 microm for MR1 spheroids, respectively, suggesting that some fundamental change in cell metabolism occurred at these characteristic diameters (denoted as "metabolic switch"). Qc(O(2)) decreased and lactate concentration increased as functions of size below the characteristic diameters. Concomitantly, glucose and lactate turnover rates decreased in MR1 spheroids and increased in Rat1-T1. Spheroids larger than the characteristic diameters (exhibiting cell quiescence and lactate accumulation) showed an enhancement of Qc(O(2)) with size. Systematic variations in the ATP and glucose levels in the viable cell rim were observed for Rat1-T1 spheroids only. Proliferative activity, Qc(O(2)), and ATP levels in small, nontumorigenic Rat1 and M1 aggregates did not differ systematically from those recorded in the largest spheroids of the corresponding ras transfectants. Unexpectedly, respiratory activity was present not only in viable but also in the morphologically disintegrated core regions of M1 aggregates. Our data suggest that myc but not ras transfection exerts major impacts on cell metabolism. Moreover, some kind of switch has been detected that triggers profound readjustment of tumor cell metabolism when proliferative activity begins to stagnate, and that is likely to initiate some other, yet unidentified energy-consuming process.

Adenosine Triphosphate↗
PubMed1997

Pigmented epithelium induces complete retinal reconstitution from dispersed embryonic chick retinae in reaggregation culture.

Reaggregation of dispersed retinal cells of the chick embryo leads to histotypic retinospheroids in which the laminar organization remains incomplete: photoreceptors form rosettes which are surrounded by constituents of the other retinal layers. Here, for the first time, a complete arrangement of layers is achieved in cellular spheres (stratoids), provided that fully dispersed retinal cells are younger than embryonic day E6, and are reaggregated in the presence of a monolayer of retinal pigmented epithelium (RPE). A remarkable mechanism of stratoid formation from 1 to 15 days in vitro is revealed by the establishment of a radial Müller glia scaffold and of photoreceptors. During the first two days of reaggregation on RPE, rosettes are still observed. At this stage immunostaining with vimentin and F11 antibodies for radial Müller glia reveal a disorganized pattern. Subsequently, radial glia processes organize into long parallel fibre bundles which are arranged like spokes to stabilize the surface and centre of the stratoid. The opsin-specific antibody CERN 901 detects photoreceptors as they gradually build up an outer nuclear layer at the surface. These findings assign to the RPE a decisive role for the genesis and regeneration of a vertebrate retina.

Animals↗
PubMed1997

Emergence of oligodendrocytes from human neural spheres.

To study the development of human oligodendrocyte precursors (OP), we expanded human embryonic brain-derived neural precursors into spheres with basic fibroblast growth factor (FGF2). Over 90% of the cells in the expanded spheres were precursors coexpressing nestin and the polysialylated (PSA) form of NCAM. The remaining cells were mostly astrocytes and neuronal cells located at the periphery of the floating spheres. When spheres were allowed to adhere on fibronectin-coated substrate in the absence of FGF2, neural precursors migrated in the outgrowth and often formed chains of cells expressing high levels of PSA-NCAM. Many migrating cells also expressed beta-3 tubulin while only scattered elongated cells radiating from the spheres were GFAP+ astrocytes. Spindle-shaped cells not associated with the chains were labeled for the PDGF-alpha receptor and often coexpressed MAP2 neuronal isoforms. Neuronal cells in the outgrowth rapidly established a rich neuritic network where OP expressing O4 and DM20/proteolipid antigens appeared. T3 treatment of neural spheres increased the rate of OP formation and the complexity of their shape. Thus, the generation of human oligodendrocytes from neural precursors is tightly correlated with growth of neuronal processes and enhanced by hormonal signals.

Brain↗
PubMed2002

Differential gene expression analysis during porcine hepatocyte spheroid formation.

Primary porcine hepatocytes cultured in suspension self-assemble into multicellular aggregates or spheroids that display enhanced liver-specific functional capability and remain viable for an extended period of time in vitro. The molecular events underlying the process of spheroid formation were explored by differential gene expression analysis. Critical time points in spheroid formation were first identified by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of stress-related gene expression levels at different stages of spheroid formation. Suppression subtractive hybridization was used to identify transcripts up- or down-regulated at different stages of spheroid formation. Subsequently, three sets of reciprocal subtractions, comparing freshly isolated hepatocytes, spheroid-forming hepatocytes, and mature spheroids were carried out, and differentially expressed transcripts were isolated, cloned, sequenced, and annotated. A total of 65 genes and 14 novel transcripts were identified as differentially expressed, and very high sequence conservation between pig and human transcripts was observed. The resultant expressed sequence tags (ESTs) revealed a rapid decrease in the transcript levels of a subset of liver-specific genes, cytochrome P450s, and enzymes involved in heme biosynthesis, as well as up-regulation of genes involved in calcium-dependent vesicle trafficking and a number of acute-phase proteins in mature spheroids. Previous morphological and functional data on hepatocyte spheroid formation support cellular polarization of the hepatocyte into apical and basolateral domains in spheroids. This is important for the re-emergence of differentiated functions in vitro and is reflected by differences in gene expression patterns.

Animals↗
PubMed2005

Pleomorphic mammalian tumor-derived bacteria self-organize as multicellular mammalian eukaryotic-like organisms: morphogenetic properties in vitro, possible origins, and possible roles in mammalian 'tumor ecologies'.

Highly pleomorphic bacteria have regularly been isolated from mammalian tumors and leukemic bloods. Here, it is shown that highly pleomorphic, cell-wall deficient bacteria derived from a mammalian tumor self-organize in vitro into mammalian tissue-like morphogenetic patterns consisting of multicellular tissue-like sheets and capillary-like networks. It is proposed that these pleomorphic mammalian tumor-derived (MTD) bacteria, during morphogenesis, express mammalian tissue morphogenesis-related genes that were acquired through eukaryote-to-prokaryote DNA transfer. Similar pleomorphic MTD bacteria might play important roles as symbiotic multicellular mammalian eukaryotic-like organisms in mammalian 'tumor ecologies' that include malignant and nonmalignant mammalian eukaryotic cells. From a mammalian tumor ecology perspective, eradication of tumors in some mammalian hosts may depend upon the elimination of pleomorphic MTD bacteria self-organized as symbiotic multicellular mammalian eukaryotic-like organisms. Further investigations of the extraordinary mammalian eukaryotic-like multicellularity of these bacteria may yield fundamental insights into the evolution of multicellularity and multicellular development and may challenge basic assumptions regarding cellular evolution.

Animals↗
PubMed1992

Radiosensitivity, repair capacity, and stem cell fraction in human soft tissue tumors: an in vitro study using multicellular spheroids and the colony assay.

Radiation doses necessary to control 50% of spheroids (SCD50) were determined for five human soft tissue tumor lines after single dose and fractionated irradiation. Spheroids with 1000-1500 cells were used throughout. A similar number of cells per spheroid resulted in different sized spheroids for the respective cell lines. The parameters alpha, beta, and the number of regenerating cellular units per spheroid (SRU) were estimated from the spheroid control data using a direct fit according to the linear quadratic model assuming Poisson statistics. The number of spheroid regenerating cellular units was also determined from the growth delay at doses required for 10% spheroid control. In addition, alpha, beta, and the fraction of clonogenic cells of the five cell lines were obtained from a soft agar colony forming assay. The most precise parameter for radiation sensitivity was the SCD50, with a coefficient of variation smaller than 5%. SCD50 values ranged from 5.9 to 11.0 Gy for the five soft tissue tumor lines. Two of the five cell lines showed significantly higher alpha values and lower calculated survival fractions after 2 Gy (SF2) in the soft agar clonogenic assay than in the spheroid control assay. This points to a resistance-enhancing effect in the spheroid system. Whereas the fractions of SRU from the number of cells per spheroid, estimated from the spheroid control and growth delay assays, agreed well, no significant correlation existed between the fraction of SRU and the fraction of clonogenic cells in the soft agar colony forming assay. The alpha/beta ratios as a descriptive measure of the fractionation sensitivity of the tumor cell spheroids in the spheroid control assay corresponded well with those derived from the dose-cell survival data using a soft agar colony forming assay. Two of the five cell lines showed high fractionation sensitivities with alpha/beta values smaller than 5 Gy while those of the remaining three ranged from 7.8 to 10.8 Gy. Spheroids are structurally more similar to in vivo tumors than monolayer cultures. From the observed lack of correlation in the radiosensitivity parameters alpha and SF2 as well as in the fraction of SRU or clonogenic cells obtained from the spheroid control assay or the colony forming assay, one would expect even greater differences between results from colony forming assays and the radiosensitivity of in vivo tumors, at least for human soft tissue sarcomas.

Cell Aggregation↗
PubMed1996

[Expression of cellular antigen of hypopharyngeal carcinoma in different culture conditions].

BACKGROUND: The need to improve therapy regimes, determine prognosis, and study biological properties of tumors extracorporally led to development of different experimental systems. In order to approach the in vivo situation, specific properties of the tumors of origin should be retained by the cells in culture over relatively long periods. However, culture conditions may change expression of cellular antigens. METHODS: Cryosections of a hypopharyngeal carcinoma were compared in this respect with different cultivation systems (2-dimensional monolayers [ML], 3-dimensional multicellular tumor spheroids [MTS] and substrate cultures on Gelita) in regard to expression of cytokeratins (CK) 1, 7, 10, 14, 18 and 19, vimentin, neurofilament (NF) kD200 and 68, ganglioside GD2, oncogene products (P53 mutant and wild), and membrane-associated antigens (HLA-ABC and -DR, epidermal growth factor receptor EGFR). RESULTS: Semiquantitative immunohistochemical methods revealed differences in expression of CK1, 14 and 19, GD2, and P53 mutant between these systems. CONCLUSION: Pronounced expression of markers in MTS compared to original biopsy and monolayer emphasizes the importance of cell-cell contact and 3-dimensionality or metabolic stress. However, weak marker expression within substrate cultures may reflect loose cell-cell contact observed. In these experiments, the antigenic configuration of MTS resembled the one of the original tumor more than the other culture systems: monolayer and growth on substrate. As vimentin and NF are not expressed by healthy epithelial cells of adults, occurrence of intratumoral vimentin and NF could point to derepression of early differentiation antigens.

Adult↗
PubMedDate not supplied

Proenzyme therapy of cancer.

Proteases and their inhibitors have long been investigated in numerous tumor systems, and at the tumor growing front, their balance has been universally found to be shifted towards higher proteolytic activities. However, out of many promising serine and metalloproteinase inhibitors, none are included in cancer treatment regimens at present. The current search for active antiproteolytic compounds is in contrast to the classical approach developed by John Beard, who suggested treating advanced cancer by fresh pancreatic extracts whose antitumor activity was based on their proteolytic potential. We followed John Beard's recommendations by using purified pancreatic proenzymes/enzymes, trypsinogen/trypsin (TG/TR), chymotrypsinogen/chymotrypsin (CG/CH) and amylase (AM). The mixture of these enzymatic activities produces potent antimetastatic and antitumor effects in cellular, animal and human systems. The treatment of cultured tumor cells with TR and CH at nanomolar [corrected] concentrations, comparable to those achieved in the blood of the patients, causes complete arrest of the directional movement of metastatic cells. Conversely, the same treatment of normal cells results in enhanced motility and an accelerated closure of the gap created in cell monolayers. Further, treatment of cells with serine proteases results in the formation of cellular 3-dimensional structures such as lamellae, cell streams and aggregates. In some cell types, the aggregates are compacted via cadherin-based cell-cell communication systems and form compact spheroids. In the highly metastatic cells with lower cadherin expression, the ability to form spheroids also diminishes. Tumor cells unable to form spheroids when treated with proteases are subject to elimination by apoptosis. In contrast, a large proportion of cells that form spheroids remain viable, although they are metabolically suppressed. Protease-treated tumor cells contain a disrupted actin cytoskeleton and exhibit a loss of front-to-back polarity. We hypothesize that the provision of zymogens, rather than the enzymes, was of crucial importance to the clinical effectiveness in the human trials conducted by Beard and his co-workers. The precursor nature of the active enzymes may offer protection against numerous serpins present in the tissues and blood. Experimental evidence supports the assertion that the conversion from proenzyme to enzyme occurs selectively on the surface of the tumor cells, but not on normal cells. We believe that this selectivity of activation is responsible for the antitumor/antimetastatic effect of proenzyme therapy and low toxicity to normal cells or tumor host. Elevated levels of endostatin and angiostatin appear in the blood of TG/CG/AM-treated tumor-bearing mice, but not in tumor mice treated with the vehicle alone or in proenzyme-treated tumor-free mice. These findings support the conclusion that proteolysis is the active mechanism of the proenzyme treatment. Future studies will focus on the molecular mechanisms of the proenzyme therapy including the identification of molecular target(s) on the tumor cells. In conclusion, we have discovered that proenzyme therapy, mandated first by John Beard nearly one hundred years ago, shows remarkable selective effects that result in growth inhibition of tumor cells with metastatic potential.

Actin Cytoskeleton↗
PubMed2000

Primary porcine hepatocytes with portal vein serum cultured on microcarriers or in spheroidal aggregates.

AIM:To develop a culture mode providing durable biomaterials with high yields and activities used in bioartificial liver.METHODS:Hepatocytes were isolated from a whole pig liver by Seglen s method of orthotopic perfusion with collagenase. In culture on microcarriers, primary porcine hepatocytes were inoculated at a concentration of 5center dot10(7)/mL into the static culture systems containing 2g/L Cytodex-3, then supplemented with 100mL/L fetal calf serum (FCS) or 100mL/L porcine portal vein serum (PPVS) respectively. In spheroidal aggregate culture hepatocytes were inoculated into 100mL siliconized flasks at a concentration of 5.0center dot10(6)/mL.RESULTS:In culture on microcarriers hepatocytes tended to aggregate on Cytodex-3 obviously after being inoculated. Typical multi-cellular aggregated spheroids could be found in the two systems 24h-48h after hepatocytes were cultured. The morphological charact-eristics and synthetic functions were maintained for 5wk in FCS culture system and 8wk in PPVS culture system. In spheroidal aggregate culture about 80%-90% isolated hepatocytes became aggregated spheroids 24h after cultured in suspension and mean diameter of the spheroids was 100&mgr;m. The relationship among the hepatocytes resembled that in the liver in vivo. Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytes cultured on monolayers.CONCLUSION:As high-yields and high-activity modes of culture on microcarriers or in spheroidal aggregate culture with portal vein serum are promising to provide biomaterials for bioartificial liver (BAL) efficiently.

Journal Article↗
PubMed1997

Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor.

Growth patterns of a number of human tumor cell lines that from three-dimensional structures of various architectures when cultured without carrier beads in a NASA rotary cell culture system are described and illustrated. The culture system, which was designed to mimic microgravity, maintained cells in suspension under very low-shear stress throughout culture. Spheroid (particulate) production occurred within a few hours after culture was started, and spheroids increased in size by cell division and fusion of small spheroids, usually stabilizing at a spheroid diameter of about 0.5 mm. Architecture of spheroids varied with cell type. Cellular interactions that occurred in spheroids resulted in conformation and shape changes of cells, and some cell lines produced complex, epithelial-like architectures. Expression of the cell adhesion molecules, CD44 and E cadherin, was upregulated in the three-dimensional constructs. Coculture of fibroblast spheroids with PC3 prostate cancer cells induced tenascin expression by the fibroblasts underlying the adherent prostate epithelial cells. Invasion of the fibroblast spheroids by the malignant epithelium was also demonstrated.

Bioreactors↗
PubMed2005

A multiscale model for avascular tumor growth.

The desire to understand tumor complexity has given rise to mathematical models to describe the tumor microenvironment. We present a new mathematical model for avascular tumor growth and development that spans three distinct scales. At the cellular level, a lattice Monte Carlo model describes cellular dynamics (proliferation, adhesion, and viability). At the subcellular level, a Boolean network regulates the expression of proteins that control the cell cycle. At the extracellular level, reaction-diffusion equations describe the chemical dynamics (nutrient, waste, growth promoter, and inhibitor concentrations). Data from experiments with multicellular spheroids were used to determine the parameters of the simulations. Starting with a single tumor cell, this model produces an avascular tumor that quantitatively mimics experimental measurements in multicellular spheroids. Based on the simulations, we predict: 1), the microenvironmental conditions required for tumor cell survival; and 2), growth promoters and inhibitors have diffusion coefficients in the range between 10(-6) and 10(-7) cm2/h, corresponding to molecules of size 80-90 kDa. Using the same parameters, the model also accurately predicts spheroid growth curves under different external nutrient supply conditions.

Animals↗
PubMed2005

Glycoprotein (gp) 96 expression: induced during differentiation of intestinal macrophages but impaired in Crohn's disease.

BACKGROUND: The glycoprotein (gp) 96 links the adaptive with the innate immune system. It is a chaperone with a binding domain for peptides generated by proteasomal degradation. During cellular stress, peptide loaded gp96 can be released and presented to T cells by antigen presenting cells (APCs). METHODS: mRNAs from in vitro differentiated macrophages (iv mac) and normal intestinal macrophages (IMACs) were compared by subtractive hybridisation and Affymetrix GeneChip analysis. Differentiation induced expression of gp96 was investigated in the multicellular spheroid (MCS) model. In vivo gp96 protein expression was detected by double labelling immunohistochemistry of human colon and in the CD4+ CD62L+ T cell transfer mouse model. RESULTS: Five of 76 clones obtained by subtractive hybridisation revealed >99% sequence homology to gp96. Affymetrix GeneChip analysis confirmed induction of gp96 in IMACs. Gp96 mRNA was detected in IMACs from normal and intestinal bowel disease mucosa. Induction of gp96 protein was observed after seven days in the MCS model of IMAC differentiation. Immunohistochemistry confirmed the presence of gp96 protein in IMACs in normal mucosa as well as in mucosa from patients with ulcerative colitis and diverticulitis. In mucosa from Crohn's disease (CD) patients, gp96 protein was not detectable. In the CD4+ CD62L+ T cell transfer mouse model, gp96 was verifiable in non-activated IMACs. CONCLUSION: Gp96 is induced during differentiation of normal IMACs but is not detected in IMACs in CD mucosa. As gp96 has been described as having a role in tolerance induction, this may be relevant for loss of tolerance against luminal bacteria found in CD patients.

Animals↗
PubMed2006

Bone marrow Oct3/4+ cells differentiate into cardiac myocytes via age-dependent paracrine mechanisms.

The mechanisms that govern the capacity of the bone marrow stem cells to generate cardiac myocytes are still unknown. Herein we demonstrate that the cardiomyogenic potential of bone marrow-derived Oct3/4(+)/cKit(+/-)/CXCR4(+/-)/CD34(-)/Sca1(-) cells is governed by age-dependent paracrine/juxtacrine platelet-derived growth factor (PDGF) pathways. Specifically, bone marrow cell cultures from both 3- and 18-month-old mice formed aggregates of Oct3/4(+) cells circumscribed by PDGFRalpha(+)/Oct3/4(-)/Sca1(+) cells. In young (3-month) bone marrow cell cultures, induction of PDGF-AB preceded the induction of cardiac genes and was required for the generation of cardiomyogenesis. Indeed, in old (18-month) cultures, diminished PDGF-B induction was associated with impaired cardiomyogenic potential, despite having Oct3/4 levels similar to those in the young cells. Importantly, supplementation with PDGF-AB specifically restored the cardiac differentiation capacity of the old bone marrow cells. Together these results demonstrate that, regardless of age, the bone marrow niche contains Oct3/4 stem cells that are capable of differentiating into cardiac myocytes. Moreover, this differentiation is governed by age-dependent PDGF-AB-mediated paracrine/juxtacrine pathways that may be essential in the translation of bone marrow cell-mediated cardiomyogenesis.

Animals↗
PubMed1992

Enhancement of transforming growth factor-alpha synthesis in multicellular tumour spheroids of A431 squamous carcinoma cells.

Multicellular tumour spheroids are cellular aggregates that can be prepared from many types of tumour cells. These three-dimensional structures provide a model for analysing the effects of cell-cell contact and intercellular microenvironments on phenomena such as autocrine regulation of growth factor synthesis. Autoregulation of the synthesis of transforming growth factor-alpha (TGF-alpha) was investigated at the message and protein levels in spheroid and monolayer cultures prepared from the A431 human squamous carcinoma cell line. The epidermal growth factor receptor (EGF-R) of these monolayer A431 cells had an average surface density of 2.2 x 10(6)/cell. Constitutive expression of TGF-alpha mRNA was an average of 3-fold greater in A431 spheroids than in monolayers, even for densely packed, confluent monolayers. This effect did not depend on hypoxic stress within the spheroids. TGF-alpha protein synthesis was enhanced in comparison with that in monolayer culture, reaching a value of up to 2-fold greater on a per cell basis. These results are discussed in the context of a TGF-alpha/EGF-R autocrine loop operating within cells that produce high local concentrations of TGF-alpha in the three-dimensional architecture of a spheroid.

Blotting, Northern↗
PubMed2003

Adenoviral transfection of hepatocytes with the thioredoxin gene confers protection against apoptosis and necrosis.

A recombinant adenovirus vector containing the human thioredoxin (TRX) gene was constructed using the Cre-loxP recombination system and used to transfect rat hepatocytes with very high efficiency. The TRX gene was expressed in a dose-dependent manner and significantly modulated rat cellular functions. The TRX gene conferred resistance to oxidative stress, such as hydrogen peroxide treatment, on the host hepatocytes. FACS analysis of DNA fragmentation showed that the TRX gene suppressed hepatocyte apoptosis. It also significantly extended the life span of hepatocytes cultured conventionally on polystyrene plates. Liver-specific functions were maintained in the viability-modulated hepatocytes. Moreover, TRX expression did not affect hepatocyte spheroid formation and it extensively suppressed necrosis in the internal cells. Thus, the transfection of hepatocytes with the TRX gene successfully confers global maintenance of liver functions. These findings provide important information for the development of bioartificial liver support systems and gene therapy for liver diseases.

Adenoviridae↗
PubMed2006

[Simulation of the growth of neurosphere cultured in bioreactors].

When the size of a neurosphere cultured in vitro reaches a certain critical value, a necrotic core will appear inside the neurosphere because of the limitation of oxygen or other nutrients transport from medium to the cells in the neurasphere. Large necrotic core will greatly reduce the expansion of NSCs. The cellular automaton (CA) model is applied in this article to model the growth of NSCs in sphere state. The appearance and enlargement of the necrotic core in a neurosphere is calculated by coupling the CA model with the nutrient diffusion analysis in bioreactors. The calculation results indicate that the culture conditions, such as seeding density, the concentration of nutrients in medium and the mass transfer coefficient between a neurosphere and medium, have some effects on the appearance of the necrotic core. However, the necrotic core mainly depends on the inner diffusion. It will certainly appear if the size of the neurosphere is large enough even the outside mass transfer is in a good condition in bioreactors. Additionally, the appearance of the necrotic core resulting from the shortage of oxygen is earlier than that caused by the limitation of glucose. And the growth of the necrotic core is very fast after its appearance, and the whole neurosphere may become necrotic. The model developed with cellular automaton and mass transfer is a good qualitative representation of NSCs growth in bioreactors.

Bioreactors↗
PubMed2004

Organ printing: fiction or science.

Aggregates of living cells (i.e. model tissue fragments) under appropriate conditions fuse like liquid drops. According to Steinberg's differential adhesion hypothesis (DAH), this may be understood by assuming that cells are motile and tissues made of such cells possess an effective surface tension. Here we show that based on these properties three-dimensional cellular structures of prescribed shape can be constructed by a novel method: cell aggregate printing. Spherical aggregates of similar size made of cells with known adhesive properties were prepared. Aggregates were embedded into biocompatible gels. When the cellular and gel properties, as well as the symmetry of the initial configuration were appropriately adjusted the contiguous aggregates fused into ring-like organ structures. To elucidate the driving force and optimal conditions for this pattern formation, Monte Carlo simulations based on a DAH motivated model were performed. The simulations reproduced the experimentally observed cellular arrangements and revealed that the control parameter of pattern evolution is the gel-tissue interfacial tension, an experimentally accessible parameter.

Biocompatible Materials↗
PubMed2006

Proliferation and death in a binary environment: a stochastic model of cellular ecosystems.

The activation, growth and death of animal cells are accompanied by changes in the chemical composition of the surrounding environment. Cells and their microscopic environment constitute therefore a cellular ecosystem whose time-evolution determines processes of interest for either biology (e.g. animal development) and medicine (e.g. tumor spreading, immune response). In this paper, we consider a general stochastic model of the interplay between cells and environmental cellular niches. Niches may be either favourable or unfavourable in sustaining cell activation, growth and death, the state of the niches depending on the state of the cells. Under the hypothesis of random coupling between the state of the environmental niche and the state of the cell, the rescaled model reduces to a set of four non-linear differential equations. The biological meaning of the model is studied and illustrated by fitting experimental data on the growth of multicellular tumor spheroids. A detailed analysis of the stochastic model, of its deterministic limit, and of normal fluctuations is provided.

Algorithms↗