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Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins
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| Zeitschriftentitel: | Cell Transplantation |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Cell Transplantation, 21, 2012, 8, S. 1613-1627 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
SAGE Publications
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| Schlagwörter: |
| author_facet |
Su, Tao Scardigli, Raffaella Fasulo, Luisa Paradiso, Beatrice Barbieri, Mario Binaschi, Anna Bovolenta, Roberta Zucchini, Silvia Cossu, Giulio Cattaneo, Antonino Simonato, Michele Su, Tao Scardigli, Raffaella Fasulo, Luisa Paradiso, Beatrice Barbieri, Mario Binaschi, Anna Bovolenta, Roberta Zucchini, Silvia Cossu, Giulio Cattaneo, Antonino Simonato, Michele |
|---|---|
| author |
Su, Tao Scardigli, Raffaella Fasulo, Luisa Paradiso, Beatrice Barbieri, Mario Binaschi, Anna Bovolenta, Roberta Zucchini, Silvia Cossu, Giulio Cattaneo, Antonino Simonato, Michele |
| spellingShingle |
Su, Tao Scardigli, Raffaella Fasulo, Luisa Paradiso, Beatrice Barbieri, Mario Binaschi, Anna Bovolenta, Roberta Zucchini, Silvia Cossu, Giulio Cattaneo, Antonino Simonato, Michele Cell Transplantation Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins Transplantation Cell Biology Biomedical Engineering |
| author_sort |
su, tao |
| spelling |
Su, Tao Scardigli, Raffaella Fasulo, Luisa Paradiso, Beatrice Barbieri, Mario Binaschi, Anna Bovolenta, Roberta Zucchini, Silvia Cossu, Giulio Cattaneo, Antonino Simonato, Michele 0963-6897 1555-3892 SAGE Publications Transplantation Cell Biology Biomedical Engineering http://dx.doi.org/10.3727/096368912x640475 <jats:p> Neurotrophic factors (NTFs) are involved in the regulation of neuronal survival and function and, thus, may be used to treat neurological diseases associated with neuronal death. A major hurdle for their clinical application is the delivery mode. We describe here a new strategy based on the use of progenitor cells called mesoangioblasts (MABs). MABs can be isolated from postnatal mesoderm tissues and, because of a high adhesin-dependent migratory capacity, can reach perivascular targets especially in damaged areas. We generated genetically modified MABs producing nerve growth factor (MABs-NGF) or brain-derived neurotrophic factor (MABs-BDNF) and assessed their bystander effects in vitro using PC12 cells, primary cultures, and organotypic cultures of adult hippocampal slices. MABs-NGF-conditioned medium induced differentiation of PC12 cells, while MABs-BDNF-conditioned medium increased viability of cultured neurons and slices. Slices cultured with MABs-BDNF medium also better retained their morphology and functional connections, and all these effects were abolished by the TrkB kinase blocker K252a or the BDNF scavenger TrkB-IgG. Interestingly, the amount of BDNF released by MABs-BDNF produced greater effects than an identical amount of recombinant BDNF, suggesting that other NTFs produced by MABs synergize with BDNF. Thus, MABs can be an effective vehicle for NTF delivery, promoting differentiation, survival, and functionality of neurons. In summary, MABs hold distinct advantages over other currently evaluated approaches for NTF delivery in the CNS, including synergy of MAB-produced NTF with the neurotrophins. Since MABs may be capable of homing into damaged brain areas, they represent a conceptually novel, promising therapeutic approach to treat neurodegenerative diseases. </jats:p> Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins Cell Transplantation |
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| title |
Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_unstemmed |
Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_full |
Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_fullStr |
Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_full_unstemmed |
Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_short |
Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_sort |
bystander effect on brain tissue of mesoangioblasts producing neurotrophins |
| topic |
Transplantation Cell Biology Biomedical Engineering |
| url |
http://dx.doi.org/10.3727/096368912x640475 |
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2012 |
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1613-1627 |
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<jats:p> Neurotrophic factors (NTFs) are involved in the regulation of neuronal survival and function and, thus, may be used to treat neurological diseases associated with neuronal death. A major hurdle for their clinical application is the delivery mode. We describe here a new strategy based on the use of progenitor cells called mesoangioblasts (MABs). MABs can be isolated from postnatal mesoderm tissues and, because of a high adhesin-dependent migratory capacity, can reach perivascular targets especially in damaged areas. We generated genetically modified MABs producing nerve growth factor (MABs-NGF) or brain-derived neurotrophic factor (MABs-BDNF) and assessed their bystander effects in vitro using PC12 cells, primary cultures, and organotypic cultures of adult hippocampal slices. MABs-NGF-conditioned medium induced differentiation of PC12 cells, while MABs-BDNF-conditioned medium increased viability of cultured neurons and slices. Slices cultured with MABs-BDNF medium also better retained their morphology and functional connections, and all these effects were abolished by the TrkB kinase blocker K252a or the BDNF scavenger TrkB-IgG. Interestingly, the amount of BDNF released by MABs-BDNF produced greater effects than an identical amount of recombinant BDNF, suggesting that other NTFs produced by MABs synergize with BDNF. Thus, MABs can be an effective vehicle for NTF delivery, promoting differentiation, survival, and functionality of neurons. In summary, MABs hold distinct advantages over other currently evaluated approaches for NTF delivery in the CNS, including synergy of MAB-produced NTF with the neurotrophins. Since MABs may be capable of homing into damaged brain areas, they represent a conceptually novel, promising therapeutic approach to treat neurodegenerative diseases. </jats:p> |
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| author | Su, Tao, Scardigli, Raffaella, Fasulo, Luisa, Paradiso, Beatrice, Barbieri, Mario, Binaschi, Anna, Bovolenta, Roberta, Zucchini, Silvia, Cossu, Giulio, Cattaneo, Antonino, Simonato, Michele |
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| description | <jats:p> Neurotrophic factors (NTFs) are involved in the regulation of neuronal survival and function and, thus, may be used to treat neurological diseases associated with neuronal death. A major hurdle for their clinical application is the delivery mode. We describe here a new strategy based on the use of progenitor cells called mesoangioblasts (MABs). MABs can be isolated from postnatal mesoderm tissues and, because of a high adhesin-dependent migratory capacity, can reach perivascular targets especially in damaged areas. We generated genetically modified MABs producing nerve growth factor (MABs-NGF) or brain-derived neurotrophic factor (MABs-BDNF) and assessed their bystander effects in vitro using PC12 cells, primary cultures, and organotypic cultures of adult hippocampal slices. MABs-NGF-conditioned medium induced differentiation of PC12 cells, while MABs-BDNF-conditioned medium increased viability of cultured neurons and slices. Slices cultured with MABs-BDNF medium also better retained their morphology and functional connections, and all these effects were abolished by the TrkB kinase blocker K252a or the BDNF scavenger TrkB-IgG. Interestingly, the amount of BDNF released by MABs-BDNF produced greater effects than an identical amount of recombinant BDNF, suggesting that other NTFs produced by MABs synergize with BDNF. Thus, MABs can be an effective vehicle for NTF delivery, promoting differentiation, survival, and functionality of neurons. In summary, MABs hold distinct advantages over other currently evaluated approaches for NTF delivery in the CNS, including synergy of MAB-produced NTF with the neurotrophins. Since MABs may be capable of homing into damaged brain areas, they represent a conceptually novel, promising therapeutic approach to treat neurodegenerative diseases. </jats:p> |
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| spelling | Su, Tao Scardigli, Raffaella Fasulo, Luisa Paradiso, Beatrice Barbieri, Mario Binaschi, Anna Bovolenta, Roberta Zucchini, Silvia Cossu, Giulio Cattaneo, Antonino Simonato, Michele 0963-6897 1555-3892 SAGE Publications Transplantation Cell Biology Biomedical Engineering http://dx.doi.org/10.3727/096368912x640475 <jats:p> Neurotrophic factors (NTFs) are involved in the regulation of neuronal survival and function and, thus, may be used to treat neurological diseases associated with neuronal death. A major hurdle for their clinical application is the delivery mode. We describe here a new strategy based on the use of progenitor cells called mesoangioblasts (MABs). MABs can be isolated from postnatal mesoderm tissues and, because of a high adhesin-dependent migratory capacity, can reach perivascular targets especially in damaged areas. We generated genetically modified MABs producing nerve growth factor (MABs-NGF) or brain-derived neurotrophic factor (MABs-BDNF) and assessed their bystander effects in vitro using PC12 cells, primary cultures, and organotypic cultures of adult hippocampal slices. MABs-NGF-conditioned medium induced differentiation of PC12 cells, while MABs-BDNF-conditioned medium increased viability of cultured neurons and slices. Slices cultured with MABs-BDNF medium also better retained their morphology and functional connections, and all these effects were abolished by the TrkB kinase blocker K252a or the BDNF scavenger TrkB-IgG. Interestingly, the amount of BDNF released by MABs-BDNF produced greater effects than an identical amount of recombinant BDNF, suggesting that other NTFs produced by MABs synergize with BDNF. Thus, MABs can be an effective vehicle for NTF delivery, promoting differentiation, survival, and functionality of neurons. In summary, MABs hold distinct advantages over other currently evaluated approaches for NTF delivery in the CNS, including synergy of MAB-produced NTF with the neurotrophins. Since MABs may be capable of homing into damaged brain areas, they represent a conceptually novel, promising therapeutic approach to treat neurodegenerative diseases. </jats:p> Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins Cell Transplantation |
| spellingShingle | Su, Tao, Scardigli, Raffaella, Fasulo, Luisa, Paradiso, Beatrice, Barbieri, Mario, Binaschi, Anna, Bovolenta, Roberta, Zucchini, Silvia, Cossu, Giulio, Cattaneo, Antonino, Simonato, Michele, Cell Transplantation, Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins, Transplantation, Cell Biology, Biomedical Engineering |
| title | Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_full | Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_fullStr | Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_full_unstemmed | Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_short | Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| title_sort | bystander effect on brain tissue of mesoangioblasts producing neurotrophins |
| title_unstemmed | Bystander Effect on Brain Tissue of Mesoangioblasts Producing Neurotrophins |
| topic | Transplantation, Cell Biology, Biomedical Engineering |
| url | http://dx.doi.org/10.3727/096368912x640475 |