+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Frontiers in Bioengineering and Biotechnology 2: 74



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057161291

Download citation: RISBibTeXText

PMID: 25566537

DOI: 10.3389/fbioe.2014.00074


Related references

Allometric scaling of indirect effects: body size ratios predict non-consumptive effects in multi-predator systems. Journal of Animal Ecology 83(6): 1461-1468, 2014

Allometric scaling law in a simple oxygen exchanging network: Possible implications on the biological allometric scaling laws. Journal of Theoretical Biology 223(2): 249-257, 21 July, 2003

Interspecies scaling of bosentan, a new endothelin receptor antagonist and integration of in vitro data into allometric scaling. Pharmaceutical Research (new York). 13(1): 97-101, 1996

Prediction of clearance in humans from in vitro human liver microsomes and allometric scaling. A comparative study of the two approaches. Drug Metabolism and Drug Interactions 19(1): 49-64, 2002

Allometric analysis of organ extraction ratios. Journal of Pharmaceutical Sciences 86(11): 1319-1320, 1997

Allometric scaling of mammalian metabolism. Journal of Experimental Biology 208(Pt 9): 1611-1619, 2005

Allometric scaling of whole stream metabolism. Ecological Society of America Annual Meeting Abstracts 88: 109, 2003

Allometric scaling laws of metabolism. Physics of Life Reviews 3(4): 229-261, 2006

In vitro effects of irritants using human skin cell and organ culture models. Clinical Research 35(3): 670A, 1987

Review on the mechanism models of allometric scaling laws 3/4 vs 2/3 power. Journal Of Plant Ecology (chinese Version): 4, 951-960, 2008

Allometric scaling of rate, age and density parameters in ecological models. Oikos 86(2): 293-310, 1999

Allometric scaling of estuarine ecosystem metabolism. Proceedings of the National Academy of Sciences of the United States of America 115(26): 6733-6738, 2018

In vitro models for cutaneous effects of glucocorticoids using human skin organ and cell culture. Maibach, H I And N J Lowe (Ed ) Models in Dermatology, Vol 4 Ix+297p S Karger Ag: Basel, Switzerland; New York, New York, Usa Illus 12-19, 1989

Allometric scaling of muscle performance and metabolism insects. Sutton, J R , G Coates And C S Houston (Ed ) Advances in The Biosciences, Vol 84 Hypoxia And Mountain Medicine; 7th International Hypoxia Symposium, Lake Louise, Alberta, Canada, February 1991 Xi+330p Pergamon Press: Oxford England, Uk; Elmsford, New York, Usa Illus 152-162, 1992

Allometric scaling of muscle performance and metabolism mammals. Sutton, J R , G Coates And C S Houston (Ed ) Advances in The Biosciences, Vol 84 Hypoxia And Mountain Medicine; 7th International Hypoxia Symposium, Lake Louise, Alberta, Canada, February 1991 Xi+330p Pergamon Press: Oxford England, Uk; Elmsford, New York, Usa Illus 143-151, 1992