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Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

Ucciferri N, Sbrana T, Ahluwalia A - Front Bioeng Biotechnol (2014)

Bottom Line: The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints.Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device.An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis.

View Article: PubMed Central - PubMed

Affiliation: CNR Institute of Clinical Physiology , Pisa , Italy ; Interdepartmental Research Center "E. Piaggio", University of Pisa , Pisa , Italy.

ABSTRACT
Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

No MeSH data available.


Related in: MedlinePlus

Morphology of C3A cells (A) and HUVEC cells in static (B) and dynamic (C) conditions.
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Figure 3: Morphology of C3A cells (A) and HUVEC cells in static (B) and dynamic (C) conditions.

Mentions: Viability and P450 activity were evaluated on each cell coated coverslip. Both cell types in both experimental models showed high viability, with very little scatter. The vitality values were within 15% of the initial vitality, indicating that cell numbers remained essentially constant during the experiments. There was no difference in hepatocyte P450 activity in all conditions (data not shown). Furthermore, hepatocyte morphology was similar to that of our static controls (Figure 3A), with endothelial cells conserving a cobblestone-like morphology in static experiments and a slightly more elongated form in dynamic experiments (Figures 3B,C).


Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

Ucciferri N, Sbrana T, Ahluwalia A - Front Bioeng Biotechnol (2014)

Morphology of C3A cells (A) and HUVEC cells in static (B) and dynamic (C) conditions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269269&req=5

Figure 3: Morphology of C3A cells (A) and HUVEC cells in static (B) and dynamic (C) conditions.
Mentions: Viability and P450 activity were evaluated on each cell coated coverslip. Both cell types in both experimental models showed high viability, with very little scatter. The vitality values were within 15% of the initial vitality, indicating that cell numbers remained essentially constant during the experiments. There was no difference in hepatocyte P450 activity in all conditions (data not shown). Furthermore, hepatocyte morphology was similar to that of our static controls (Figure 3A), with endothelial cells conserving a cobblestone-like morphology in static experiments and a slightly more elongated form in dynamic experiments (Figures 3B,C).

Bottom Line: The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints.Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device.An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis.

View Article: PubMed Central - PubMed

Affiliation: CNR Institute of Clinical Physiology , Pisa , Italy ; Interdepartmental Research Center "E. Piaggio", University of Pisa , Pisa , Italy.

ABSTRACT
Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

No MeSH data available.


Related in: MedlinePlus