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Piras, Elena
Publications (6 of 6) Show all publications
Fransson, M., Piras, E., Wang, H., Burman, J., Duprez, I., Harris, R. A., . . . Loskog, A. S. (2014). Intranasal Delivery of CNS-Retargeted Human Mesenchymal Stromal Cells Prolongs Treatment Efficacy of Experimental Autoimmune Encephalomyelitis. Immunology, 142(3), 431-441
Open this publication in new window or tab >>Intranasal Delivery of CNS-Retargeted Human Mesenchymal Stromal Cells Prolongs Treatment Efficacy of Experimental Autoimmune Encephalomyelitis
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2014 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 142, no 3, p. 431-441Article in journal (Refereed) Published
Abstract [en]

Treatment with mesenchymal stromal cells (MSC) is currently of interest for a number of diseases including multiple sclerosis (MS). MSCs is well known to target inflamed tissues however, in a therapeutic scenery, systemic administration will lead to few cells reaching the brain. We hypothesized that MSCs may target the brain upon intranasal (i.n) administration and persist in CNS tissue if expressing a CNS-targeting receptor. To demonstrate proof of concept, MSCs were genetically engineered to express a myelin oligodendrocyte glycoprotein (MOG)-specific receptor. Engineered MSCs retained their immunosuppressive capacity, infiltrated into the brain upon i.n. cell administration, and were able to significantly reduce disease symptoms of experimental autoimmune encephalomyelitis (EAE). The mice treated with CNS-targeting MSCs were resistant to further EAE induction whereas non-targeted MSC did not give such persistent effects. Histological analysis revealed increased brain restoration in engineered MSC-treated mice. In conclusion, MSCs can be genetically engineered to target the brain and prolong therapeutic efficacy in an EAE model.

National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-223631 (URN)10.1111/imm.12275 (DOI)000337600500012 ()24588452 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2014-04-23 Created: 2014-04-23 Last updated: 2018-05-18Bibliographically approved
Fransson, M., Piras, E., Burman, J., Nilsson, B., Essand, M., Lu, B., . . . Loskog, A. S. (2012). CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery. Journal of Neuroinflammation, 9, 112
Open this publication in new window or tab >>CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery
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2012 (English)In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 9, p. 112-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation of stable CNS-targeting Tregs needs further development. Here, we propose gene engineering to achieve CNS-targeting Tregs from naive CD4 cells and demonstrate their efficacy in the EAE model.

METHODS

CD4+T cells were modified utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were administered by intranasal (i.n.) cell delivery.

RESULTS

The engineered Tregs demonstrated suppressive capacity in vitro and could efficiently access various regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were treated and the engineered Tregs suppressed ongoing encephalomyelitis as demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered Tregs compared to controls. Symptomfree mice were echallenged with a second EAE-inducing inoculum but remained healthy, demonstrating the sustained effect of engineered Tregs.

CONCLUSION

CNS-targeting Tregs delivered i.n. localized to the CNS and efficiently suppressed ongoing inflammation leading to diminished disease symptoms.

Keywords
MS, redirected cells, T regulatory cells, EAE, FoxP3, myelin oligodendrocyte glycoprotein
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-175383 (URN)10.1186/1742-2094-9-112 (DOI)000307014500001 ()22647574 (PubMedID)
Note

De två första författarna delar första författarskapet.

Available from: 2012-06-05 Created: 2012-06-05 Last updated: 2018-05-18Bibliographically approved
Piras, E. (2006). Drugs in the olfactory pathways: bioactivation, toxicity and transfer to the brain.. (Licentiate dissertation).
Open this publication in new window or tab >>Drugs in the olfactory pathways: bioactivation, toxicity and transfer to the brain.
2006 (English)Licentiate thesis, monograph (Other scientific)
Identifiers
urn:nbn:se:uu:diva-86496 (URN)
Available from: 2007-02-05 Created: 2007-02-05
Piras, E., Franzén, A., Fernández, E. L., Bergström, U., Raffalli-Mathieu, F., Lang, M. & Brittebo, E. B. (2003). Cell-specific expression of CYP2A5 in the mouse respiratory tract: effects of olfactory toxicants.. Journal of Histochemistry and Cytochemistry, 51(11), 1545-1555
Open this publication in new window or tab >>Cell-specific expression of CYP2A5 in the mouse respiratory tract: effects of olfactory toxicants.
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2003 (English)In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 51, no 11, p. 1545-1555Article in journal (Refereed) Published
Abstract [en]

We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells. In the respiratory and transitional epithelium there was no or only weak expression. The nasolacrimal duct and the excretory ducts of nasal and salivary glands displayed expression, whereas no expression occurred in the acini. There was decreasing expression along the epithelial linings of the trachea and lower respiratory tract, whereas no expression occurred in the alveoli. The hepatic CYP2A5 inducers pyrazole and phenobarbital neither changed the CYP2A5 expression pattern nor damaged the olfactory mucosa. In contrast, the olfactory toxicants dichlobenil and methimazole induced characteristic changes. The damaged Bowman's glands displayed no expression, whereas the damaged epithelium expressed the enzyme. The CYP2A5 expression pattern is in accordance with previously reported localization of protein and DNA adducts and the toxicity of some CYP2A5 substrates. This suggests that CYP2A5 is an important determinant for the susceptibility of the nasal and respiratory epithelia to protoxicants and procarcinogens.

Keywords
Animals, Aryl Hydrocarbon Hydroxylases/*biosynthesis, Environmental Pollutants/*toxicity, Enzyme Induction, Female, Immunohistochemistry, In Situ Hybridization, Male, Methimazole/toxicity, Mice, Mice, Inbred DBA, Mixed Function Oxygenases/*biosynthesis, Nasolacrimal Duct/cytology/drug effects/metabolism, Nitriles/toxicity, Olfactory Mucosa/cytology/drug effects/metabolism, Phenobarbital/toxicity, Pyrazoles/toxicity, Respiratory System/cytology/drug effects/*metabolism, Salivary Glands/cytology/drug effects/metabolism, Support, Non-U.S. Gov't
National Category
Biological Sciences
Research subject
Ecotoxicology
Identifiers
urn:nbn:se:uu:diva-67120 (URN)14566026 (PubMedID)
Available from: 2008-11-28 Created: 2008-11-28 Last updated: 2017-11-28Bibliographically approved
Franzén, A., Piras, E., Bergström, U., Fernandez, E. L., Raffalli-Mathieu, F., Lang, M. & Brittebo, E. (2003). Effects of olfactory toxicants on the expression of CYP2A2. In: Toxicology Letters 144, Suppl 1,: (pp. 153-).
Open this publication in new window or tab >>Effects of olfactory toxicants on the expression of CYP2A2
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2003 (English)In: Toxicology Letters 144, Suppl 1,, 2003, p. 153-Conference paper, Published paper (Other scientific)
Identifiers
urn:nbn:se:uu:diva-78293 (URN)
Available from: 2008-11-28 Created: 2008-11-28
Bergström, U., Giovanetti, A., Piras, E. & Brittebo, E. (2003). Methimazole-induced damage in the olfactory mucosa: effects on ultrastructure and glutathione levels.. Toxicol Pathol, 31(4), 379-87
Open this publication in new window or tab >>Methimazole-induced damage in the olfactory mucosa: effects on ultrastructure and glutathione levels.
2003 (English)In: Toxicol Pathol, ISSN 0192-6233, Vol. 31, no 4, p. 379-87Article in journal (Refereed) Published
Keywords
Animals, Antithyroid Agents/*toxicity, Dose-Response Relationship; Drug, Glutathione/*drug effects, Liver/drug effects, Methimazole/*toxicity, Mice, Microscopy; Electron, Olfactory Mucosa/*drug effects/pathology/ultrastructure, Olfactory Receptor Neurons/drug effects, Support; Non-U.S. Gov't, Time Factors
Identifiers
urn:nbn:se:uu:diva-67095 (URN)12851103 (PubMedID)
Available from: 2008-11-28 Created: 2008-11-28
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