CLAUDIA REGINA CECCHI

CLAUDIA REGINA CECCHI

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Efficient non-invasive plasmid-DNA administration into tibialis cranialis muscle of “little” mice
2017 - CECCHI, C.R.; HIGUTI, E.; LIMA, E.R.; VIEIRA, D.P.; SQUAIR, P.L.; PERONI, C.N.; BARTOLINI, P.
Background: An alternative treatment for growth hormone deficiency based on hGH-DNA administration, followed by electro gene transfer, was investigated by injecting the plasmid into surgically exposed or non-exposed quadriceps or tibialis muscle of immunodeficient “little” mice. Methods: An optimization of electrotransfer conditions via a new combination of high/low voltage pulses is presented. After 3 days, serum hGH was determined and in a 28-day assay, the relative growth parameters were compared. Results: Both groups exhibited similar results: 5.0 ± 2.2 (SD) and 3.5 ± 0.9 ng hGH/ml (P>0.05; n=7) for the exposed quadriceps and non-exposed tibialis treatments, respectively. The final body weight increases were 16.1% for the quadriceps and 18.9% for the tibialis group. The tail and nose-to-tail length increases were 4.5% and 7.1% for the quadriceps and 4.8 and 4.6% for the tibialis group. The right and left femur length increases, obtained from radiographic measurements, were 16.9% and 12.7% for the quadriceps and 19.4% and 12.3% for the tibialis, respectively. A non-significant difference between exposed quadriceps and non-exposed tibialis treatments (P=0.48) was confirmed via a completely integrated statistical analysis. Circulating mIGF-1 levels were 126 ± 47, 106 ± 93 (P>0.05) and 38 ± 15 ng/ml for the quadriceps, tibialis and saline treatments, respectively. Conclusion: These results show that hGH-DNA administration into non-exposed tibialis muscle followed by the new HV/LV electrotransfer protocol was an equally efficient, less traumatic treatment,
Modelos de terapia gênica baseados na expressão de hormônio de crescimento em células humanas e na administração de DNA plasmidial em camundongos anões
2015 - PERONI, CIBELE N.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; BARTOLINI, PAOLO
A novel homologous model for gene therapy of swarfism by non-viral transfer of the mouse growth hormone gene into immunocompetent dwarf mice
2014 - CECCHI, CLAUDIA R.; HIGUTI, ELIZA; OLIVEIRA, NELIO A.J.; LIMA, ELIANA R.; JAKOBSEN, MARIA; DAGNAES-HANSEN, FREDERIK; BARTOLINI, PAOLO; PERONI, CIBELE N.
Growth responses following a single intra-muscular hGH plasmid administration compared to daily injections of hGH in dwarf mice
2012 - HIGUTI, ELIZA; CECCHI, CLAUDIA R.; OLIVEIRA, NELIO A.J.; VIEIRA, DANIEL P.; JENSEN, THOMAS G.; JORGE, ALEXANDER A.L.; BARTOLINI, PAOLO; PERONI, CIBELE N.
Long-term human growth hormone expression and partial phenotypic correction by plasmid-base gene therapy in an animal model of isolated growth hormone deficiency
2010 - OLIVEIRA, NELIO A.J.; CECCHI, CLAUDIA R.; HIGUTI, ELIZA; OLIVEIRA, JOAO E.; JENSEN, THOMAS G.; BARTOLINI, PAOLO; PERONI, CIBELE N.
Secretion of mouse growth hormone by transduced primary human keratinocytes: prospects for an animal model of cutaneous gene therapy
2008 - PERONI, CIBELE N.; CECCHI, CLAUDIA R.; ROSAURO, CRISTIANE W.; NONOGAKI, SUELY; BOCCARDO, ENRIQUE; BARTOLINI, PAOLO
Background: 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.