Dataset Information

Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

ABSTRACT: Therapeutic application of mesenchymal stem cells (MSC) requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM) that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

SUBMITTER: Hoffmann M

PROVIDER: S-EPMC3132757 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

Hoffmann Martin M Kuska Jens-Peer JP Zscharnack Matthias M Loeffler Markus M Galle Joerg J

PloS one 20110708 7

Therapeutic application of mesenchymal stem cells (MSC) requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM) that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitl ...[more]

PMID: 21760935

Similar Datasets

Project description:In simulation models of populations or communities, individual plants have often been obfuscated in favor of aggregated vegetation. This simplification comes with a loss of biological detail and a smoothing out of the demographic noise engendered by stochastic individual-scale processes and heterogeneities, which is significant among others when studying the viability of small populations facing challenging fluctuating environmental conditions. This consideration has motivated the development of precise plant-centered models. The accuracy gained in the representation of plant biology has then, however, often been balanced by the disappearance in models of important plant-soil interactions (esp. water dynamics) due to the inability of most individual-based frameworks to simulate complex continuous processes. In this study, we used a hybrid modeling approach, namely integrated System Dynamics (SD)-Individual-based (IB), to illustrate the importance of individual plant dynamics to explain spatial self-organization of vegetation in arid environments. We analyzed the behavior of this model under different parameter sets either related to individual plant properties (such as seed dispersal distance and reproductive age) or the environment (such as intensity and yearly distribution of precipitation events). While the results of this work confirmed the prevailing theory on vegetation patterning, they also revealed the importance therein of plant-level processes that cannot be rendered by reaction-diffusion models. Initial spatial distribution of plants, reproductive age, and average seed dispersal distance, by impacting patch size and vegetation aggregation, affected pattern formation and population survival under climatic variations. Besides, changes in precipitation regime altered the demographic structure and spatial organization of vegetation patches by affecting plants differentially depending on their age and biomass. Water availability influenced non-linearly total biomass density. Remarkably, lower precipitation resulted in lower mean plant age yet higher mean individual biomass. Moreover, seasonal variations in rainfall greater than a threshold (here, ±0.45 mm from the 1.3 mm baseline) decreased mean total biomass and generated limit cycles, which, in the case of large variations, were preceded by chaotic demographic and spatial behavior. In some cases, peculiar spatial patterns (e.g., rings) were also engendered. On a technical note, the shortcomings of the present model and the benefit of hybrid modeling for virtual investigations in plant science are discussed.

Project description:BackgroundHuman mesenchymal stem cells (hMSCs) are multipotent by nature and are originally isolated from bone marrow. In light of a future application of hMSCs in the oral cavity, a body compartment with varying oxygen partial pressures and an omnipresence of different bacterial species i.e. periodontitis pathogens, we performed this study to gain information about the behavior of hMSC in an anaerobic system and the response in interaction with oral bacterial pathogens.Methodology/principal findingsWe established a model system with oral pathogenic bacterial species and eukaryotic cells cultured in anaerobic conditions. The facultative anaerobe bacteria Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were studied. Their effects on hMSCs and primary as well as permanent gingival epithelial cells (Ca9-22, HGPEC) were comparatively analyzed. We show that hMSCs cope with anoxic conditions, since 40% vital cells remain after 72 h of anaerobic culture. The Ca9-22 and HGPEC cells are significantly more sensitive to lack of oxygen. All bacterial species reveal a comparatively low adherence to and internalization into hMSCs (0.2% and 0.01% of the initial inoculum, respectively). In comparison, the Ca9-22 and HGPEC cells present better targets for bacterial adherence and internalization. The production of the pro-inflammatory chemokine IL-8 is higher in both gingival epithelial cell lines compared to hMSCs and Fusobacterium nucleatum induce a time-dependent cytokine secretion in both cell lines. Porphyromonas gingivalis is less effective in stimulating secretion of IL-8 in the co-cultivation experiments.Conclusions/significanceHMSCs are suitable for use in anoxic regions of the oral cavity. The interaction with local pathogenic bacteria does not result in massive pro-inflammatory cytokine responses. The test system established in this study allowed further investigation of parameters prior to set up of oral hMSC in vivo studies.

Dataset Information

Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

Publications

Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets