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Adenoviral mediated delivery of OSKM factors induces partial reprogramming of mouse cardiac cells in vivo
Kisby, Thomas (The University of Manchester. Nanomedicine Lab.)
de Lázaro, Irene (Wyss Institute for Biologically Inspired Engineering at Harvard University. Center for Life Science)
Fisch, Sudeshna (Harvard Medical School)
Cartwright, Elizabeth J. (Manchester Academic Health Science Centre)
Cossu, Giulio (The University of Manchester. Faculty of Biology, Medicine and Health)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)

Data: 2021
Resum: The induction of in vivo reprogramming toward pluripotency has been demonstrated in several tissues utilizing either transgenic inducible mice or gene delivery approaches. However, the effects of exogenous reprogramming factor expression in the mammalian heart have not been previously reported. The present study aims to investigate the response of cardiac cells to ectopic Oct3/4, Sox2, Klf4, and cMyc (OSKM) expression in vivo using a non-integrating adenoviral vector. Direct intramyocardial injection of this vector achieves effective and transient OSKM overexpression in the healthy heart and after myocardial infarction. The expression of these factors induces transient upregulation of a number of endogenous pluripotency (endo-Oct3/4, Gdf3) and reprogramming related (Cdh1, Fut4) genes, confirming the induction of cell reprogramming. Despite the initiation of reprogramming, markers of fully de-differentiated cells including Nanog remain silenced, consistent with a partially reprogrammed state. Furthermore, no indications of tumorigenesis or teratoma formation are observed. Overall, these data suggest that adenoviral mediated OSKM delivery can be utilized to induce partial in vivo reprogramming. However, the absence of any clear regenerative effects after myocardial infarction indicates that further optimization of vector mediated reprogramming strategies is essential to overcome barriers to therapeutic efficacy.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Adenovirus ; Cardiovascular ; Gene therapy ; Pluripotency ; Reprogramming
Publicat a: Advanced Therapeutics, Vol. 4, issue 2 (Feb. 2021) , art. 2000141, ISSN 2366-3987

DOI: 10.1002/adtp.202000141


9 p, 4.9 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències > Institut Català de Nanociència i Nanotecnologia (ICN2)
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2021-12-20, darrera modificació el 2022-09-11



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