FABIO LUIZ NAVARRO MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Mesenchymal Stem Cells Do Not Prevent Antibody Responses against Human alpha-L-Iduronidase when Used to Treat Mucopolysaccharidosis Type I(2014) MARTIN, Priscila Keiko Matsumoto; STILHANO, Roberta Sessa; SAMOTO, Vivian Yochiko; TAKIYA, Christina Maeda; PERES, Giovani Bravin; MICHELACCI, Yara Maria Correa da Silva; SILVA, Flavia Helena da; PEREIRA, Vanessa Goncalves; D'ALMEIDA, Vania; MARQUES, Fabio Luiz Navarro; OTAKE, Andreia Hanada; CHAMMAS, Roger; HAN, Sang WonMucopolysaccharidosis type I (MPSI) is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of alpha-L-iduronidase (IDUA). Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. For cell transplantation, 4x10(6) MSC-KO-IDUA cells (MSC from KO mice modified with IDUA) were injected into the peritoneum of KO-mice three times over intervals of more than one month. The total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. The antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. The spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of In-111-labeled MSC. In conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases.
conferenceObject 7-Ketocholesterol loaded-phosphatidylserine liposome induces cell death, autophagy, and growth inhibition of melanoma and breast adenocarcinoma.(2018) FAVERO, Giovani Marino; TORTELLI JR., Tharcisio Citrangulo; FERNANDES, Daniel; PRESTES, Ana Paula; KMETIUK, Louise N. B.; OTAKE, Andreia Hanada; ANDRADE, Luciana N. S.; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; MARQUES, Fabio L. N.; CHAMMAS, Roger- Melanoma and breast adenocarcinoma growth inhibition by a 7-ketocholesterol loaded-phosphatidylserine liposome(2018) FAVERO, Giovani M.; TORTELLI, Tharcisio C.; OTAKE, Andreia H.; ANDRADE, Luciana N.; FARIA, Daniele P.; CARNEIRO, Camila G.; GARCEZ, Alexandre T.; MARQUES, Fabio L.; CHAMMAS, Roger