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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

The MCmB connection scheme for the whole-body MSSM (A) and the abdominal CNSM (B).
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Figure 2: The MCmB connection scheme for the whole-body MSSM (A) and the abdominal CNSM (B).

Mentions: In this work, we used four (monolayer) hepatocyte chambers and one endothelial chamber to represent whole-body MSSM type scaling. The abdominal CNSM configuration was composed of one hepatocyte chamber and one endothelial chamber. All dynamic experiments were carried out in five MCmB modules connected in series as shown in Figure 2. For the MSSM, one endothelial cell coated slide was placed in the bottom of the first chamber and four hepatocyte slides were transferred to each of the other chambers of the system (Figure 2A). In the CNSM, one endothelial slide was placed in the bottom of the first chamber and one hepatocyte slide in the second chamber, the other three chambers were left empty of cells (Figure 2B). Each bottom part of the chamber was filled with 500 μL of common media in order to avoid drying of cells during assembly of the system. The rest of the common media (15 mL in total, necessary to fill the circuit and avoid nutrient depletion) was added to the mixing bottle. The circuits were closed and connected to a pump (Ismatech IPC-4, Zurich, Switzerland) and run at 100 μL/min in the incubator for 72 h.


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

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

The MCmB connection scheme for the whole-body MSSM (A) and the abdominal CNSM (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: The MCmB connection scheme for the whole-body MSSM (A) and the abdominal CNSM (B).
Mentions: In this work, we used four (monolayer) hepatocyte chambers and one endothelial chamber to represent whole-body MSSM type scaling. The abdominal CNSM configuration was composed of one hepatocyte chamber and one endothelial chamber. All dynamic experiments were carried out in five MCmB modules connected in series as shown in Figure 2. For the MSSM, one endothelial cell coated slide was placed in the bottom of the first chamber and four hepatocyte slides were transferred to each of the other chambers of the system (Figure 2A). In the CNSM, one endothelial slide was placed in the bottom of the first chamber and one hepatocyte slide in the second chamber, the other three chambers were left empty of cells (Figure 2B). Each bottom part of the chamber was filled with 500 μL of common media in order to avoid drying of cells during assembly of the system. The rest of the common media (15 mL in total, necessary to fill the circuit and avoid nutrient depletion) was added to the mixing bottle. The circuits were closed and connected to a pump (Ismatech IPC-4, Zurich, Switzerland) and run at 100 μL/min in the incubator for 72 h.

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