Changes in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivo

dc.creatorNaujok, Ortwin
dc.creatorFrancini, Flavio
dc.creatorPicton, Sally
dc.creatorBailey, Clifford J.
dc.creatorLenzen, Sigurd
dc.creatorJörns, Anne
dc.date2009-07
dc.identifierhttp://hdl.handle.net/11336/96669
dc.identifierNaujok, Ortwin; Francini, Flavio; Picton, Sally; Bailey, Clifford J.; Lenzen, Sigurd; et al.; Changes in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivo; John Wiley & Sons Ltd; Diabetes/metabolism Research and Reviews; 25; 5; 7-2009; 464-476
dc.identifier1520-7552
dc.identifierCONICET Digital
dc.identifierCONICET
dc.descriptionBackground: Embryonic stem (ES) cells have the potential to produce unlimited numbers of surrogate insulin-producing cells for cell replacement therapy of type 1 diabetes mellitus. The impact of the in vivo environment on mouse ES cell differentiation towards insulin-producing cells was analysed morphologically after implantation. Methods: ES cells differentiated in vitro into insulin-producing cells according to the Lumelsky protocol or a new four-stage differentiation protocol were analysed morphologically before and after implantation for gene expression by in situ reverse transcription polymerase chain reaction and protein expression by immunohistochemistry and ultrastructural analysis. Results: In comparison with nestin positive ES cells developed according to the reference protocol, the number of ES cells differentiated with the four-stage protocol increased under in vivo conditions upon morphological analysis. The cells exhibited, in comparison to the in vitro situation, increased gene and protein expression of Pdx1, insulin, islet amyloid polypeptide (IAPP), the GLUT2 glucose transporter and glucokinase, which are functional markers for glucose-induced insulin secretion of pancreatic beta cells. Renal sub-capsular implantation of ES cells with a higher degree of differentiation achieved by in vitro differentiation with a four-stage protocol enabled further significant maturation for the beta-cell-specific markers, insulin and the costored IAPP as well as the glucose recognition structures. In contrast, further in vivo differentiation was not achieved with cells differentiated in vitro by the reference protocol. Conclusions: A sufficient degree of in vitro differentiation is an essential prerequisite for further substantial maturation in a beta-cell-specific way in vivo, supported by cell-cell contacts and vascularisation.
dc.descriptionFil: Naujok, Ortwin. Hannover Medical School; Alemania
dc.descriptionFil: Francini, Flavio. Hannover Medical School; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina
dc.descriptionFil: Picton, Sally. Aston University; Reino Unido
dc.descriptionFil: Bailey, Clifford J.. Aston University; Reino Unido
dc.descriptionFil: Lenzen, Sigurd. Hannover Medical School; Alemania
dc.descriptionFil: Jörns, Anne. Hannover Medical School; Alemania
dc.formatapplication/pdf
dc.formatapplication/msword
dc.formatapplication/pdf
dc.languageeng
dc.publisherJohn Wiley & Sons Ltd
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1002/dmrr.965
dc.relationinfo:eu-repo/semantics/altIdentifier/url/onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.965
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subjectDIFFERENTIATION
dc.subjectINSULIN CELL THERAPY
dc.subjectINSULIN-PRODUCING CELLS
dc.subjectMOUSE EMBRYONIC STEM CELLS
dc.subjecthttps://purl.org/becyt/ford/3.2
dc.subjecthttps://purl.org/becyt/ford/3
dc.titleChanges in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivo
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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