Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy
Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflamm...
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| creator | Oses, Carolina Olivares, Belén Ezquer, Marcelo Acosta, Cristian Bosch, Paul Donoso, Macarena Léniz, Patricio Ezquer, Fernando |
| description | Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment. |
| doi_str_mv | 10.1371/journal.pone.0178011 |
| format | Article |
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Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0178011</identifier><identifier>PMID: 28542352</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Activation analysis ; Adipose tissue ; Adipose Tissue - cytology ; Adipose Tissue - drug effects ; Adipose Tissue - metabolism ; Adult ; AKT protein ; Amputation ; Angiogenesis ; Animal models ; Anti-inflammatory agents ; Anti-Inflammatory Agents - metabolism ; Apoptosis ; Apoptosis - drug effects ; Attenuation ; Autonomic nervous system ; Biocompatibility ; Biology and Life Sciences ; Biomolecules ; Blood ; Blood flow ; Body fat ; Bone marrow ; Cardiology ; Cardiovascular diseases ; Care and treatment ; Cell Proliferation - drug effects ; Cells, Cultured ; Cues ; Deferoxamine ; Deferoxamine - pharmacology ; Degeneration ; Diabetes ; Diabetes mellitus ; Diabetic neuropathies ; Diabetic Neuropathies - immunology ; Diabetic Neuropathies - metabolism ; Diabetic Neuropathies - prevention & control ; Diabetic neuropathy ; Dialysis ; Differentiation ; Disease ; Dosage and administration ; Drug therapy ; Extremities ; Female ; Gene therapy ; Glial cells ; Glucose ; Health aspects ; Heart diseases ; Humans ; Hypoxia ; Incidence ; Inflammation ; Inflammation - immunology ; Inflammation - metabolism ; Inflammation - prevention & control ; Inhibition ; Inhibitors ; Interferon ; Iron ; Medicine and Health Sciences ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mesenchymal Stromal Cells - metabolism ; Metabolism ; Middle Aged ; Modulation ; Neovascularization, Physiologic - drug effects ; Nervous system ; Neurodegeneration ; Neurons ; Neuroprotective Agents - metabolism ; Neurosciences ; Neurotrophic factors ; Oxidative stress ; Pain ; Pain perception ; Pharmacology ; Poisoning ; Quality of life ; Rats ; Reduction ; Regeneration (physiology) ; Restoration ; Siderophores - pharmacology ; Stem cells ; Tissues ; Toxicology ; Transplantation ; Transplants & implants ; Vascular endothelial growth factor ; Velocity ; Young Adult</subject><ispartof>PloS one, 2017-05, Vol.12 (5), p.e0178011-e0178011</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Oses et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Oses et al 2017 Oses et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-9a62c747ba73eb6bf3b60a2afdb8a49e533f38c085bb5936611586f8c6acd1593</citedby><cites>FETCH-LOGICAL-c692t-9a62c747ba73eb6bf3b60a2afdb8a49e533f38c085bb5936611586f8c6acd1593</cites><orcidid>0000-0002-7696-4215</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438173/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438173/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28542352$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oses, Carolina</creatorcontrib><creatorcontrib>Olivares, Belén</creatorcontrib><creatorcontrib>Ezquer, Marcelo</creatorcontrib><creatorcontrib>Acosta, Cristian</creatorcontrib><creatorcontrib>Bosch, Paul</creatorcontrib><creatorcontrib>Donoso, Macarena</creatorcontrib><creatorcontrib>Léniz, Patricio</creatorcontrib><creatorcontrib>Ezquer, Fernando</creatorcontrib><title>Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Activation analysis</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - cytology</subject><subject>Adipose Tissue - drug effects</subject><subject>Adipose Tissue - metabolism</subject><subject>Adult</subject><subject>AKT protein</subject><subject>Amputation</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Anti-inflammatory agents</subject><subject>Anti-Inflammatory Agents - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Attenuation</subject><subject>Autonomic nervous system</subject><subject>Biocompatibility</subject><subject>Biology and Life Sciences</subject><subject>Biomolecules</subject><subject>Blood</subject><subject>Blood flow</subject><subject>Body fat</subject><subject>Bone marrow</subject><subject>Cardiology</subject><subject>Cardiovascular diseases</subject><subject>Care and treatment</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Cues</subject><subject>Deferoxamine</subject><subject>Deferoxamine - pharmacology</subject><subject>Degeneration</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic neuropathies</subject><subject>Diabetic Neuropathies - immunology</subject><subject>Diabetic Neuropathies - metabolism</subject><subject>Diabetic Neuropathies - prevention & control</subject><subject>Diabetic neuropathy</subject><subject>Dialysis</subject><subject>Differentiation</subject><subject>Disease</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Extremities</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Glial cells</subject><subject>Glucose</subject><subject>Health aspects</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Incidence</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - prevention & control</subject><subject>Inhibition</subject><subject>Inhibitors</subject><subject>Interferon</subject><subject>Iron</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Modulation</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Nervous system</subject><subject>Neurodegeneration</subject><subject>Neurons</subject><subject>Neuroprotective Agents - metabolism</subject><subject>Neurosciences</subject><subject>Neurotrophic factors</subject><subject>Oxidative stress</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Pharmacology</subject><subject>Poisoning</subject><subject>Quality of life</subject><subject>Rats</subject><subject>Reduction</subject><subject>Regeneration (physiology)</subject><subject>Restoration</subject><subject>Siderophores - pharmacology</subject><subject>Stem cells</subject><subject>Tissues</subject><subject>Toxicology</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Vascular endothelial growth factor</subject><subject>Velocity</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQaG0UG8ty8deFELoIRBI6OlWjKWxV8GWHElOs8_cl6i8cUK25KIYI3v0zT8zGk0UPafJirKSvj83k9XQr0ajcZXQskoofRDt05qlcZEm7OGd773oiXPnSZKzqigeR3tplWcpy9P96M-ZRWG0VF4ZrXRHTEtAqtE4JF45N2Es0apLlGRAh1qsNwP0xHkciMC-d-S38msisUVrrmBQGonSwiI4dMSvkYzWyEnM8rN2-ItBd8p0qJV4RzRO1gSjx4BcIgEtw-tVrHTbwzCAN3ZDWhBhdR_IWQDDbsgAxrFXAra6Sm8j-RDVD2F_DiQVNOiVWCKAX2-eRo9a6B0-W9aD6OfnTz-OvsYnp1-Ojw5PYlHUqY9rKFJRZmUDJcOmaFrWFAmk0MqmgqzGnLGWVSKp8qbJa1YUlOZV0VaiACFpsBxEL691x944vvTJcVonCcuTNM8DcXxNSAPnfLRqALvhBhTfGoztONiQfI9cirQqC0lDLnUmhGzapihpCyDKvGqaLGh9XKJNzYBShPot9DuiuztarXlnLnmesSrIBoE3i4A1FxM6zwfl5t6CRjNt82a0SFKaBvTVP-j91S1UB6GA0EgT4opZlB9mdZrUIeyc9-oeKjwSBxWuJLYq2Hcc3u44BMbjle9gco4ff__2_-zpr1329R12jdD7tTP9NF8ttwtm16CwxjmL7e0h04TPM3lzGnyeSb7MZHB7cbdBt043Q8j-Alw2Olk</recordid><startdate>20170519</startdate><enddate>20170519</enddate><creator>Oses, Carolina</creator><creator>Olivares, Belén</creator><creator>Ezquer, Marcelo</creator><creator>Acosta, Cristian</creator><creator>Bosch, Paul</creator><creator>Donoso, Macarena</creator><creator>Léniz, Patricio</creator><creator>Ezquer, Fernando</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7696-4215</orcidid></search><sort><creationdate>20170519</creationdate><title>Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy</title><author>Oses, Carolina ; Olivares, Belén ; Ezquer, Marcelo ; Acosta, Cristian ; Bosch, Paul ; Donoso, Macarena ; Léniz, Patricio ; Ezquer, Fernando</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-9a62c747ba73eb6bf3b60a2afdb8a49e533f38c085bb5936611586f8c6acd1593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Activation analysis</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - cytology</topic><topic>Adipose Tissue - drug effects</topic><topic>Adipose Tissue - metabolism</topic><topic>Adult</topic><topic>AKT protein</topic><topic>Amputation</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Anti-inflammatory agents</topic><topic>Anti-Inflammatory Agents - metabolism</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Attenuation</topic><topic>Autonomic nervous system</topic><topic>Biocompatibility</topic><topic>Biology and Life Sciences</topic><topic>Biomolecules</topic><topic>Blood</topic><topic>Blood flow</topic><topic>Body fat</topic><topic>Bone marrow</topic><topic>Cardiology</topic><topic>Cardiovascular diseases</topic><topic>Care and treatment</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Cues</topic><topic>Deferoxamine</topic><topic>Deferoxamine - pharmacology</topic><topic>Degeneration</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic neuropathies</topic><topic>Diabetic Neuropathies - immunology</topic><topic>Diabetic Neuropathies - metabolism</topic><topic>Diabetic Neuropathies - prevention & control</topic><topic>Diabetic neuropathy</topic><topic>Dialysis</topic><topic>Differentiation</topic><topic>Disease</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Extremities</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Glial cells</topic><topic>Glucose</topic><topic>Health aspects</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Incidence</topic><topic>Inflammation</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - prevention & control</topic><topic>Inhibition</topic><topic>Inhibitors</topic><topic>Interferon</topic><topic>Iron</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Modulation</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Nervous system</topic><topic>Neurodegeneration</topic><topic>Neurons</topic><topic>Neuroprotective Agents - metabolism</topic><topic>Neurosciences</topic><topic>Neurotrophic factors</topic><topic>Oxidative stress</topic><topic>Pain</topic><topic>Pain perception</topic><topic>Pharmacology</topic><topic>Poisoning</topic><topic>Quality of life</topic><topic>Rats</topic><topic>Reduction</topic><topic>Regeneration (physiology)</topic><topic>Restoration</topic><topic>Siderophores - pharmacology</topic><topic>Stem cells</topic><topic>Tissues</topic><topic>Toxicology</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><topic>Vascular endothelial growth factor</topic><topic>Velocity</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oses, Carolina</creatorcontrib><creatorcontrib>Olivares, Belén</creatorcontrib><creatorcontrib>Ezquer, Marcelo</creatorcontrib><creatorcontrib>Acosta, Cristian</creatorcontrib><creatorcontrib>Bosch, Paul</creatorcontrib><creatorcontrib>Donoso, Macarena</creatorcontrib><creatorcontrib>Léniz, Patricio</creatorcontrib><creatorcontrib>Ezquer, Fernando</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oses, Carolina</au><au>Olivares, Belén</au><au>Ezquer, Marcelo</au><au>Acosta, Cristian</au><au>Bosch, Paul</au><au>Donoso, Macarena</au><au>Léniz, Patricio</au><au>Ezquer, Fernando</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-05-19</date><risdate>2017</risdate><volume>12</volume><issue>5</issue><spage>e0178011</spage><epage>e0178011</epage><pages>e0178011-e0178011</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28542352</pmid><doi>10.1371/journal.pone.0178011</doi><tpages>e0178011</tpages><orcidid>https://orcid.org/0000-0002-7696-4215</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-05, Vol.12 (5), p.e0178011-e0178011 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1900350255 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Activation analysis Adipose tissue Adipose Tissue - cytology Adipose Tissue - drug effects Adipose Tissue - metabolism Adult AKT protein Amputation Angiogenesis Animal models Anti-inflammatory agents Anti-Inflammatory Agents - metabolism Apoptosis Apoptosis - drug effects Attenuation Autonomic nervous system Biocompatibility Biology and Life Sciences Biomolecules Blood Blood flow Body fat Bone marrow Cardiology Cardiovascular diseases Care and treatment Cell Proliferation - drug effects Cells, Cultured Cues Deferoxamine Deferoxamine - pharmacology Degeneration Diabetes Diabetes mellitus Diabetic neuropathies Diabetic Neuropathies - immunology Diabetic Neuropathies - metabolism Diabetic Neuropathies - prevention & control Diabetic neuropathy Dialysis Differentiation Disease Dosage and administration Drug therapy Extremities Female Gene therapy Glial cells Glucose Health aspects Heart diseases Humans Hypoxia Incidence Inflammation Inflammation - immunology Inflammation - metabolism Inflammation - prevention & control Inhibition Inhibitors Interferon Iron Medicine and Health Sciences Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - metabolism Metabolism Middle Aged Modulation Neovascularization, Physiologic - drug effects Nervous system Neurodegeneration Neurons Neuroprotective Agents - metabolism Neurosciences Neurotrophic factors Oxidative stress Pain Pain perception Pharmacology Poisoning Quality of life Rats Reduction Regeneration (physiology) Restoration Siderophores - pharmacology Stem cells Tissues Toxicology Transplantation Transplants & implants Vascular endothelial growth factor Velocity Young Adult |
| title | Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy |
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