Microenvironment Modulates Osteogenic Cell Lineage Commitment in Differentiated Embryonic Stem Cells 英文参考文献.docVIP

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Microenvironment Modulates Osteogenic Cell Lineage Commitment in Differentiated Embryonic Stem Cells 英文参考文献.doc

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Microenvironment Modulates Osteogenic Cell Lineage Commitment in Differentiated Embryonic Stem Cells 英文参考文献

MicroenvironmentModulatesOsteogenicCellLineage CommitmentinDifferentiatedEmbryonicStemCells AkihiroYamashita,SandiNishikawa,DerrickE.Rancourt* DepartmentofBiochemistryandMolecularBiology,UniversityofCalgary,Calgary,Alberta,Canada Abstract Background: Due to their self-renewal, embryonic stem cells (ESCs) are attractive cells for applications in regenerative medicineandtissueengineering.AlthoughESCdifferentiationhasbeenusedasaplatformforgeneratingboneinvitroand invivo,theresultshavebeenunsatisfactory atbest.Itispossible thatthetraditionalculturemethods,whichhavebeen used,arenotoptimalandthatotherapproachesmustbeexplored. Methodology/Principal Findings: ESCs were differentiated into osteoblast lineage using a micro-mass approach. In responsetoosteogenicdifferentiationmedium,manycellsunderwentapoptosis,whileothersleftthemicro-mass,forming small aggregates in suspension. These aggregates were cultured in three different culture conditions (adhesion, static suspension,andstirredsuspension),thenexaminedforosteogenicpotentialinvitroandinvivo.Inadhesionculture,ESCs primedtobecomeosteoblastsrecommittedtotheadipocytelineageinvitro.Inastaticsuspensionculture,resultingporous aggregates expressed osteoblasts markers and formed bone in vivo via intermembranous ossification. In a stirred suspensionculture,resultingnon-porousaggregatessuppressedosteoblastdifferentiationinfavorofexpandingprogenitor cells. Conclusions/Significance: We demonstrate that microenvironment modulates cell fate and subsequent tissue formation during ESC differentiation. For effective tissue engineering using ESCs, it is important to develop optimized cell culture/ differentiationconditionsbasedupontheinfluenceofmicroenvironment. Citation:YamashitaA,NishikawaS,RancourtDE(2010)MicroenvironmentModulatesOsteogenicCellLineageCommitmentinDifferentiatedEmbryonicStem Cells.PLoSONE5(3):e9663.doi:10.1371/journal.pone.0009663 Editor:SyedA.Aziz,HealthCanada,Canada ReceivedOctober23,2009;AcceptedDecember9,2009;Pu