Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin
Abstract Background Islets of Langerhans transplantation is a promising therapy for type 1 diabetes mellitus, but this technique is compromised by transplantation stresses including inflammation. In other tissues, co-transplantation with mesenchymal stem cells has been shown to reduce damage by impr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1190-4 |
| _version_ | 1818981605615599616 |
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| author | Camille Laporte Emily Tubbs Justine Cristante Anne-Sophie Gauchez Sandra Pesenti Frédéric Lamarche Cécile Cottet-Rousselle Catherine Garrel Anaick Moisan Jean-Marc Moulis Eric Fontaine Pierre-Yves Benhamou Sandrine Lablanche |
| author_facet | Camille Laporte Emily Tubbs Justine Cristante Anne-Sophie Gauchez Sandra Pesenti Frédéric Lamarche Cécile Cottet-Rousselle Catherine Garrel Anaick Moisan Jean-Marc Moulis Eric Fontaine Pierre-Yves Benhamou Sandrine Lablanche |
| author_sort | Camille Laporte |
| collection | DOAJ |
| description | Abstract Background Islets of Langerhans transplantation is a promising therapy for type 1 diabetes mellitus, but this technique is compromised by transplantation stresses including inflammation. In other tissues, co-transplantation with mesenchymal stem cells has been shown to reduce damage by improving anti-inflammatory and anti-oxidant defences. Therefore, we probed the protection afforded by bone marrow mesenchymal stem cells to islets under pro-inflammatory cytokine stress. Methods In order to evaluate the cytoprotective potential of mesenchymal stem cells on rat islets, co-cultures were exposed to the interleukin-1, tumour necrosis factor α and interferon γ cocktail for 24 h. Islet viability and functionality tests were performed. Reactive oxygen species and malondialdehyde were measured. Expression of stress-inducible genes acting as anti-oxidants and detoxifiers, such as superoxide dismutases 1 and 2, NAD(P)H quinone oxidoreductase 1, heme oxygenase-1 and ferritin H, was compared to non-stressed cells, and the corresponding proteins were measured. Data were analysed by a two-way ANOVA followed by a Holm-Sidak post hoc analysis. Results Exposure of rat islets to cytokines induces a reduction in islet viability and functionality concomitant with an oxidative status shift with an increase of cytosolic ROS production. Mesenchymal stem cells did not significantly increase rat islet viability under exposure to cytokines but protected islets from the loss of insulin secretion. A drastic reduction of the antioxidant factors heme oxygenase-1 and ferritin H protein levels was observed in islets exposed to the cytokine cocktail with a prevention of this effect by the presence of mesenchymal stem cells. Conclusions Our data evidenced that MSCs are able to preserve islet insulin secretion through a modulation of the oxidative imbalance mediated by heme and iron via heme oxygenase-1 and ferritin in a context of cytokine exposure. |
| first_indexed | 2024-12-20T17:33:59Z |
| format | Article |
| id | doaj.art-6c7c89b474e04d04860bd2723576abe0 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-20T17:33:59Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-6c7c89b474e04d04860bd2723576abe02022-12-21T19:31:16ZengBMCStem Cell Research & Therapy1757-65122019-03-0110111210.1186/s13287-019-1190-4Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritinCamille Laporte0Emily Tubbs1Justine Cristante2Anne-Sophie Gauchez3Sandra Pesenti4Frédéric Lamarche5Cécile Cottet-Rousselle6Catherine Garrel7Anaick Moisan8Jean-Marc Moulis9Eric Fontaine10Pierre-Yves Benhamou11Sandrine Lablanche12Laboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesBiology Institute, Grenoble Alpes University HospitalUniv Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1Laboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesBiology Institute, Grenoble Alpes University HospitalCell Therapy and Engineering Unit, EFS Auvergne-Rhône-AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesLaboratory of Fundamental and Applied Bioenergetics (LBFA), INSERM U 1055 and SFR Environmental and Systems Biology (BEeSy), University Grenoble AlpesAbstract Background Islets of Langerhans transplantation is a promising therapy for type 1 diabetes mellitus, but this technique is compromised by transplantation stresses including inflammation. In other tissues, co-transplantation with mesenchymal stem cells has been shown to reduce damage by improving anti-inflammatory and anti-oxidant defences. Therefore, we probed the protection afforded by bone marrow mesenchymal stem cells to islets under pro-inflammatory cytokine stress. Methods In order to evaluate the cytoprotective potential of mesenchymal stem cells on rat islets, co-cultures were exposed to the interleukin-1, tumour necrosis factor α and interferon γ cocktail for 24 h. Islet viability and functionality tests were performed. Reactive oxygen species and malondialdehyde were measured. Expression of stress-inducible genes acting as anti-oxidants and detoxifiers, such as superoxide dismutases 1 and 2, NAD(P)H quinone oxidoreductase 1, heme oxygenase-1 and ferritin H, was compared to non-stressed cells, and the corresponding proteins were measured. Data were analysed by a two-way ANOVA followed by a Holm-Sidak post hoc analysis. Results Exposure of rat islets to cytokines induces a reduction in islet viability and functionality concomitant with an oxidative status shift with an increase of cytosolic ROS production. Mesenchymal stem cells did not significantly increase rat islet viability under exposure to cytokines but protected islets from the loss of insulin secretion. A drastic reduction of the antioxidant factors heme oxygenase-1 and ferritin H protein levels was observed in islets exposed to the cytokine cocktail with a prevention of this effect by the presence of mesenchymal stem cells. Conclusions Our data evidenced that MSCs are able to preserve islet insulin secretion through a modulation of the oxidative imbalance mediated by heme and iron via heme oxygenase-1 and ferritin in a context of cytokine exposure.http://link.springer.com/article/10.1186/s13287-019-1190-4Diabetes mellitus type 1Islets of Langerhans transplantationMesenchymal stem cellsCo-cultureCytokinesHeme oxygenase 1 |
| spellingShingle | Camille Laporte Emily Tubbs Justine Cristante Anne-Sophie Gauchez Sandra Pesenti Frédéric Lamarche Cécile Cottet-Rousselle Catherine Garrel Anaick Moisan Jean-Marc Moulis Eric Fontaine Pierre-Yves Benhamou Sandrine Lablanche Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin Stem Cell Research & Therapy Diabetes mellitus type 1 Islets of Langerhans transplantation Mesenchymal stem cells Co-culture Cytokines Heme oxygenase 1 |
| title | Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin |
| title_full | Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin |
| title_fullStr | Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin |
| title_full_unstemmed | Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin |
| title_short | Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin |
| title_sort | human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase 1 and ferritin |
| topic | Diabetes mellitus type 1 Islets of Langerhans transplantation Mesenchymal stem cells Co-culture Cytokines Heme oxygenase 1 |
| url | http://link.springer.com/article/10.1186/s13287-019-1190-4 |
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