Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism
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 towards building an integrated picture of syst...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-12-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fbioe.2014.00074/full |
| _version_ | 1818199245821313024 |
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| author | Nadia eUcciferri Tommaso eSbrana Arti eAhluwalia Arti eAhluwalia |
| author_facet | Nadia eUcciferri Tommaso eSbrana Arti eAhluwalia Arti eAhluwalia |
| author_sort | Nadia eUcciferri |
| collection | DOAJ |
| description | 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 towards building an integrated picture of systemic metabolism and signalling 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 analyse the physiologic 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, CNSM, and Metabolic and Surface Scaling model, MSSM) 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 condition. |
| first_indexed | 2024-12-12T02:18:42Z |
| format | Article |
| id | doaj.art-fb221da0474e438ca92f8c1041df459b |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-12T02:18:42Z |
| publishDate | 2014-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-fb221da0474e438ca92f8c1041df459b2022-12-22T00:41:45ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852014-12-01210.3389/fbioe.2014.00074119695Allometric scaling and cell ratios in multi-organ in vitro models of human metabolismNadia eUcciferri0Tommaso eSbrana1Arti eAhluwalia2Arti eAhluwalia3CNRUniversity of PisaUniversity of PisaCNRIntelligent 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 towards building an integrated picture of systemic metabolism and signalling 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 analyse the physiologic 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, CNSM, and Metabolic and Surface Scaling model, MSSM) 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 condition.http://journal.frontiersin.org/Journal/10.3389/fbioe.2014.00074/fullEndothelial CellsMetabolismAllometryIn-vitro modelsorgan-on-a-platehepatoctes |
| spellingShingle | Nadia eUcciferri Tommaso eSbrana Arti eAhluwalia Arti eAhluwalia Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism Frontiers in Bioengineering and Biotechnology Endothelial Cells Metabolism Allometry In-vitro models organ-on-a-plate hepatoctes |
| title | Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism |
| title_full | Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism |
| title_fullStr | Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism |
| title_full_unstemmed | Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism |
| title_short | Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism |
| title_sort | allometric scaling and cell ratios in multi organ in vitro models of human metabolism |
| topic | Endothelial Cells Metabolism Allometry In-vitro models organ-on-a-plate hepatoctes |
| url | http://journal.frontiersin.org/Journal/10.3389/fbioe.2014.00074/full |
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