In vivo studies on non-viral transdifferentiation of liver cells towards pancreatic β cells

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dc.contributor.authorÇim, Abdullah
dc.contributor.authorSawyer, Greta Jane
dc.contributor.authorZhang, Xiaohong
dc.contributor.authorSu, Haibin
dc.contributor.authorCollins, Louise
dc.contributor.authorJones, Peter
dc.contributor.authorAntoniou, Michael
dc.date.accessioned2024-04-24T17:56:43Z
dc.date.available2024-04-24T17:56:43Z
dc.date.issued2012
dc.departmentDicle Üniversitesien_US
dc.description.abstractTransdifferentiation in vivo is an attractive option for autologous replacement of pancreatic ? cells in patients with type 1 diabetes. It has been achieved by adenoviral delivery of genes for transcription factors in the liver and pancreas of hyperglycaemic mice. However, these viral approaches are not clinically applicable. We used the hydrodynamic approach to deliver genes Pdx1, Ngn3 (Neurog3) and MafA singly and in combination to livers of normoglycaemic rats. Five expression plasmids were evaluated. Livers were removed 1, 3, 7, 14 and 28 days after gene delivery and assayed by quantitative PCR, semi-quantitative PCR and immunohistology. Functional studies on hyperglycaemic rats were performed. The highest and most sustained expression was from a CpG-depleted plasmid (pCpG) and a plasmid with an in-frame scaffold/matrix attachment region ((pEPI(CMV)). When Pdx1, Ngn3 and MafA were delivered together to normoglycaemic rats with these plasmids, insulin mRNA was detected at all time points and was ~50-fold higher with pCpG. Insulin mRNA content of livers at days 3 and 7 was equivalent to that of a pancreas, with scattered insulin-positive cells detected by immunohistology, but levels declined thereafter. Prohormone convertase 1/3 was elevated at days 3 and 7. In hyperglycaemic rats, fasting blood glucose was lower at days 1, 3 and 7 but not thereafter, and body weight was maintained to day 28. We conclude that hydrodynamic gene delivery of multiple transcription factors to rat liver can initiate transdifferentiation to pancreatic ? cells, but the process is reversible and probably requires more sustained transcription factor expression.en_US
dc.identifier.citationÇim, A., Sawyer, G. J., Zhang, X., Su, H., Collins, L., Jones, P. ve diğerleri. (2012). In vivo studies on non-viral transdifferentiation of liver cells towards pancreatic β cells. Journal of Endocrinology, 214(3), 277-288.
dc.identifier.doi10.1530/JOE-12-0033
dc.identifier.endpage288en_US
dc.identifier.issn0022-0795
dc.identifier.issue3en_US
dc.identifier.pmid22685335
dc.identifier.scopus2-s2.0-84866298387
dc.identifier.scopusqualityQ1
dc.identifier.startpage277en_US
dc.identifier.urihttps://doi.org/10.1530/JOE-12-0033
dc.identifier.urihttps://hdl.handle.net/11468/23638
dc.identifier.volume214en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.relation.ispartofJournal of Endocrinology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleIn vivo studies on non-viral transdifferentiation of liver cells towards pancreatic β cellsen_US
dc.titleIn vivo studies on non-viral transdifferentiation of liver cells towards pancreatic ? cells
dc.typeArticleen_US

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