Secretion of mouse growth hormone by transduced primary human keratinocytes: prospects for an animal model of cutaneous gene therapy

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dc.contributor.authorPERONI, CIBELE N.pt_BR
dc.contributor.authorCECCHI, CLAUDIA R.pt_BR
dc.contributor.authorROSAURO, CRISTIANE W.pt_BR
dc.contributor.authorNONOGAKI, SUELYpt_BR
dc.contributor.authorBOCCARDO, ENRIQUEpt_BR
dc.contributor.authorBARTOLINI, PAOLOpt_BR
dc.coverageInternacionalpt_BR
dc.date.accessioned2014-07-15T13:43:28Zpt_BR
dc.date.accessioned2014-07-30T11:49:59Z
dc.date.available2014-07-15T13:43:28Zpt_BR
dc.date.available2014-07-30T11:49:59Z
dc.date.issued2008pt_BR
dc.description.abstractBackground: Keratinocytes are a very attractive vehicle for ex vivo gene transfer and systemic delivery because proteins secreted by these cells may reach the circulation via a mechanism that mimics the natural process. Methods: An efficient retroviral vector (LXSN) encoding the mouse growth hormone gene (mGH) was used to transduce primary human keratinocytes. Organotypic raft cultures were prepared with these genetically modified keratinocytes and were grafted onto immunodeficient dwarf mice (lit/scid). Results: Transduced keratinocytes presented a high and stable in vitro secretion level of up to 11 µg mGH/106cells/day. Conventional epidermal sheets made with these genetically modified keratinocytes, however, showed a drop in secretion rates of > 80% due to detachment of the epithelium from its substratum. Substitution of conventional grafting methodologies with organotypic raft cultures completely overcame this problem. The stable long-term grafting of such cultures onto lit/scid mice could be followed for more than 4 months, and a significant weight increase over the control group was observed in the first 40 days. Circulating mGH levels revealed a peak of 21 ng/ml just 1 h after grafting but, unfortunately, these levels rapidly fell to baseline values. Conclusions: mGH-secreting primary human keratinocytes presented the highest in vitro expression and peak circulatory levels reported to date for a form of GH with this type of cells. Together with previous data showing that excised implants can recover a remarkable fraction of their original in vitro mGH secretion efficiency in culture, the factors that might still hamper the success of this promising model of cutaneous gene therapy are discussed.
dc.format.extent734-743pt_BR
dc.identifier.citationPERONI, CIBELE N.; CECCHI, CLAUDIA R.; ROSAURO, CRISTIANE W.; NONOGAKI, SUELY; BOCCARDO, ENRIQUE; BARTOLINI, PAOLO. Secretion of mouse growth hormone by transduced primary human keratinocytes: prospects for an animal model of cutaneous gene therapy. <b>Journal of Gene Medicine</b>, v. 10, p. 734-743, 2008. DOI: <a href="https://dx.doi.org/10.1002/jgm.1196">10.1002/jgm.1196</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/5033.
dc.identifier.doi10.1002/jgm.1196
dc.identifier.issn1099-498Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-8194-5230
dc.identifier.urihttp://repositorio.ipen.br/handle/123456789/5033pt_BR
dc.identifier.vol10pt_BR
dc.relation.ispartofJournal of Gene Medicinept_BR
dc.rightsclosedAccessen
dc.subjectmicept_BR
dc.subjectanimal growthpt_BR
dc.subjectgene therapypt_BR
dc.subjectkeratinpt_BR
dc.subjectepidermispt_BR
dc.subjectanimal cellspt_BR
dc.subjectin vitropt_BR
dc.titleSecretion of mouse growth hormone by transduced primary human keratinocytes: prospects for an animal model of cutaneous gene therapypt_BR
dc.typeArtigo de periódicopt_BR
dspace.entity.typePublication
ipen.autorPAOLO BARTOLINI
ipen.autorCRISTIANE WANDERLEY ROSAURO
ipen.autorCLAUDIA REGINA CECCHI
ipen.autorCIBELE NUNES PERONI
ipen.codigoautor1503
ipen.codigoautor2866
ipen.codigoautor3865
ipen.codigoautor947
ipen.contributor.ipenauthorPAOLO BARTOLINI
ipen.contributor.ipenauthorCRISTIANE WANDERLEY ROSAURO
ipen.contributor.ipenauthorCLAUDIA REGINA CECCHI
ipen.contributor.ipenauthorCIBELE NUNES PERONI
ipen.date.recebimento09-02pt_BR
ipen.identifier.fi3.141pt_BR
ipen.identifier.ipendoc13178pt_BR
ipen.identifier.iwosWoSpt_BR
ipen.range.fi3.000 - 4.499
ipen.type.genreArtigo
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relation.isAuthorOfPublication.latestForDiscoveryc30bdc49-9059-4fa3-91a9-7c92d7cd1dab
sigepi.autor.atividadePERONI, CIBELE N.:947:810:Spt_BR
sigepi.autor.atividadeCECCHI, CLAUDIA R.:3865:810:Npt_BR
sigepi.autor.atividadeROSAURO, CRISTIANE W.:2866:-1:Npt_BR
sigepi.autor.atividadeBARTOLINI, PAOLO:1503:810:Npt_BR
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