Agent Based Modelling Helps in Understanding the Rules by Which Fibroblasts Support Keratinocyte Colony Formation 英文参考文献.docVIP
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Agent Based Modelling Helps in Understanding the Rules by Which Fibroblasts Support Keratinocyte Colony Formation 英文参考文献
AgentBasedModellingHelpsinUnderstandingthe
RulesbyWhichFibroblastsSupportKeratinocyteColony
Formation
TaoSun1*,PhilMcMinn2,MikeHolcombe2,RodSmallwood2,SheilaMacNeil1*
1DepartmentofEngineeringMaterials,UniversityofSheffield,Sheffield,UnitedKingdom,2DepartmentofComputerScience,UniversityofSheffield,Sheffield,United
Kingdom
Abstract
Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for
clinicaluse.Withgrowingconcernsaboutthesafetyofthesexenobioticmaterials,itisdesirabletoculturekeratinocytesin
mediawithoutanimalderivedproducts.Animprovedunderstandingofepithelial/mesenchymalinteractionscouldassistin
this.
Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based
keratinocytecolonyformationmodeltoincludetheresponseofkeratinocytestobothfibroblastsandserum.Themodel
wasvalidatedbycomparisonoftheinvirtuoandinvitromulticellularbehaviourofkeratinocytesandfibroblastsinsingle
andco-cultureinGreensmedium.Totesttherobustnessofthemodel,severalpropertiesofthefibroblastswerechangedto
investigatetheirinfluenceonthemulticellularmorphogenesisofkeratinocyesandfibroblasts.Themodelwasthenusedto
generatehypothesestoexploretheinteractionsofbothproliferativeandgrowtharrestedfibroblastswithkeratinocytes.
The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of
fibroblaststokeratinocyteswouldcriticallyinfluencekeratinocytecolonyexpansion,2)thisrationeededtobeoptimumat
the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding
keratinocytesand4)inthepresenceofanadequatenumberoffibroblasts,keratinocyteexpansionwouldbeindependent
ofserum.
Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex
biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this stu
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