Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells
Aims/hypothesis The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequ...
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| Veröffentlicht in: | Diabetologia 2018-11, Vol.61 (11), p.2371-2385 |
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| creator | Hajmousa, Ghazaleh Przybyt, Ewa Pfister, Frederick Paredes-Juarez, Genaro A. Moganti, Kondaiah Busch, Stephanie Kuipers, Jeroen Klaassen, Ingeborg van Luyn, Marja J. A. Krenning, Guido Hammes, Hans-Peter Harmsen, Martin C. |
| description | Aims/hypothesis
The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequent aberrant angiogenesis.
Methods
We investigated the pericytic function of ASCs after intravitreal injection of ASCs in mice with retinopathy of prematurity as a model for clinical diabetic retinopathy. In addition, ASCs influence their environment by paracrine signalling. For this, we assessed the immunomodulatory capacity of conditioned medium from cultured ASCs (ASC-Cme) on high glucose (HG)-stimulated bovine retinal endothelial cells (BRECs).
Results
ASCs augmented and stabilised retinal angiogenesis and co-localised with capillaries at a pericyte-specific position. This indicates that cultured ASCs exert juxtacrine signalling in retinal microvessels. ASC-Cme alleviated HG-induced oxidative stress and its subsequent upregulation of downstream targets in an NF-κB dependent fashion in cultured BRECs. Functionally, monocyte adhesion to the monolayers of activated BRECs was also decreased by treatment with ASC-Cme and correlated with a decline in expression of adhesion-related genes such as
SELE
,
ICAM1
and
VCAM1
.
Conclusions/interpretation
The ability of ASC-Cme to immunomodulate HG-challenged BRECs is related to the length of time for which ASCs were preconditioned in HG medium. Conditioned medium from ASCs that had been chronically exposed to HG medium was able to normalise the HG-challenged BRECs to normal glucose levels. In contrast, conditioned medium from ASCs that had been exposed to HG medium for a shorter time did not have this effect. Our results show that the manner of HG preconditioning of ASCs dictates their immunoregulatory properties and thus the potential outcome of treatment of diabetic retinopathy. |
| doi_str_mv | 10.1007/s00125-018-4713-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2095529481</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2095529481</sourcerecordid><originalsourceid>FETCH-LOGICAL-p212t-3370a15d8406ba393989e178514bc2dec69e6b2fdb77480feb3d42742f95509f3</originalsourceid><addsrcrecordid>eNpdkU2L1TAUhoMoznXGH-BGAm7cxDn5aJsuZVBHGHAzwuxK2pzem6FNaz4u3F_lXzT1ziC4OpDz5DkvvIS84_CJAzTXEYCLigHXTDVcMnhBdlxJwUAJ_ZLstjXjun64IG9ifAQAWan6NbmQwCte82pHft_m2XhqrFuXiDS5GDMyi8Ed0dKYwjKbiQ44TZGaIVET6Zj9kNziy_tauOGUMFLn6ewGpMaXX3ldA8ZID25_YPspD0XNnLd5KM41LM6Pk5lnk5Zw2qzuaDYhXUbaL0fnkQZMbjuA3i7pgJN7DnFFXo1mivj2aV6Sn1-_3N_csrsf377ffL5jq-AiMSkbMLyyWkHdG9nKVrfIG11x1Q_C4lC3WPditH3TKA0j9tIq0SgxtlUF7Sgvycezt8T9lTGmbnZxS2A8Ljl2AgooWqV5QT_8hz4uOZT0fynZgpa6KtT7Jyr3M9puDW424dQ9V1EAcQZiWfk9hn8aDt3Wd3fuuyt9d1vfHcg_T92e0Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2093908385</pqid></control><display><type>article</type><title>Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Hajmousa, Ghazaleh ; Przybyt, Ewa ; Pfister, Frederick ; Paredes-Juarez, Genaro A. ; Moganti, Kondaiah ; Busch, Stephanie ; Kuipers, Jeroen ; Klaassen, Ingeborg ; van Luyn, Marja J. A. ; Krenning, Guido ; Hammes, Hans-Peter ; Harmsen, Martin C.</creator><creatorcontrib>Hajmousa, Ghazaleh ; Przybyt, Ewa ; Pfister, Frederick ; Paredes-Juarez, Genaro A. ; Moganti, Kondaiah ; Busch, Stephanie ; Kuipers, Jeroen ; Klaassen, Ingeborg ; van Luyn, Marja J. A. ; Krenning, Guido ; Hammes, Hans-Peter ; Harmsen, Martin C.</creatorcontrib><description>Aims/hypothesis
The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequent aberrant angiogenesis.
Methods
We investigated the pericytic function of ASCs after intravitreal injection of ASCs in mice with retinopathy of prematurity as a model for clinical diabetic retinopathy. In addition, ASCs influence their environment by paracrine signalling. For this, we assessed the immunomodulatory capacity of conditioned medium from cultured ASCs (ASC-Cme) on high glucose (HG)-stimulated bovine retinal endothelial cells (BRECs).
Results
ASCs augmented and stabilised retinal angiogenesis and co-localised with capillaries at a pericyte-specific position. This indicates that cultured ASCs exert juxtacrine signalling in retinal microvessels. ASC-Cme alleviated HG-induced oxidative stress and its subsequent upregulation of downstream targets in an NF-κB dependent fashion in cultured BRECs. Functionally, monocyte adhesion to the monolayers of activated BRECs was also decreased by treatment with ASC-Cme and correlated with a decline in expression of adhesion-related genes such as
SELE
,
ICAM1
and
VCAM1
.
Conclusions/interpretation
The ability of ASC-Cme to immunomodulate HG-challenged BRECs is related to the length of time for which ASCs were preconditioned in HG medium. Conditioned medium from ASCs that had been chronically exposed to HG medium was able to normalise the HG-challenged BRECs to normal glucose levels. In contrast, conditioned medium from ASCs that had been exposed to HG medium for a shorter time did not have this effect. Our results show that the manner of HG preconditioning of ASCs dictates their immunoregulatory properties and thus the potential outcome of treatment of diabetic retinopathy.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-018-4713-0</identifier><identifier>PMID: 30151615</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adipose tissue ; Adipose Tissue - cytology ; Angiogenesis ; Animals ; Capillaries ; Cattle ; Cell Adhesion - drug effects ; Cell Survival - drug effects ; Cells, Cultured ; Diabetes ; Diabetes mellitus ; Diabetic retinopathy ; Diabetic Retinopathy - metabolism ; E-Selectin - metabolism ; Endothelial cells ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Glucose ; Glucose - pharmacology ; Human Physiology ; Humans ; Immunomodulation ; Immunoregulation ; Inflammation ; Intercellular adhesion molecule 1 ; Intercellular Adhesion Molecule-1 - metabolism ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Mice ; Mice, Inbred C57BL ; Monocytes ; Monocytes - drug effects ; Monocytes - metabolism ; NF-κB protein ; Oxidative stress ; Oxidative Stress - drug effects ; Paracrine signalling ; Pericytes ; Pericytes - cytology ; Pericytes - drug effects ; Retina ; Retina - cytology ; Retinopathy ; Signal Transduction - drug effects ; Stromal cells ; Stromal Cells - cytology ; Vascular Cell Adhesion Molecule-1 - metabolism ; Wound Healing - drug effects</subject><ispartof>Diabetologia, 2018-11, Vol.61 (11), p.2371-2385</ispartof><rights>The Author(s) 2018</rights><rights>Diabetologia is a copyright of Springer, (2018). All Rights Reserved. © 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p212t-3370a15d8406ba393989e178514bc2dec69e6b2fdb77480feb3d42742f95509f3</cites><orcidid>0000-0001-7428-3312</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-018-4713-0$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-018-4713-0$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30151615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hajmousa, Ghazaleh</creatorcontrib><creatorcontrib>Przybyt, Ewa</creatorcontrib><creatorcontrib>Pfister, Frederick</creatorcontrib><creatorcontrib>Paredes-Juarez, Genaro A.</creatorcontrib><creatorcontrib>Moganti, Kondaiah</creatorcontrib><creatorcontrib>Busch, Stephanie</creatorcontrib><creatorcontrib>Kuipers, Jeroen</creatorcontrib><creatorcontrib>Klaassen, Ingeborg</creatorcontrib><creatorcontrib>van Luyn, Marja J. A.</creatorcontrib><creatorcontrib>Krenning, Guido</creatorcontrib><creatorcontrib>Hammes, Hans-Peter</creatorcontrib><creatorcontrib>Harmsen, Martin C.</creatorcontrib><title>Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequent aberrant angiogenesis.
Methods
We investigated the pericytic function of ASCs after intravitreal injection of ASCs in mice with retinopathy of prematurity as a model for clinical diabetic retinopathy. In addition, ASCs influence their environment by paracrine signalling. For this, we assessed the immunomodulatory capacity of conditioned medium from cultured ASCs (ASC-Cme) on high glucose (HG)-stimulated bovine retinal endothelial cells (BRECs).
Results
ASCs augmented and stabilised retinal angiogenesis and co-localised with capillaries at a pericyte-specific position. This indicates that cultured ASCs exert juxtacrine signalling in retinal microvessels. ASC-Cme alleviated HG-induced oxidative stress and its subsequent upregulation of downstream targets in an NF-κB dependent fashion in cultured BRECs. Functionally, monocyte adhesion to the monolayers of activated BRECs was also decreased by treatment with ASC-Cme and correlated with a decline in expression of adhesion-related genes such as
SELE
,
ICAM1
and
VCAM1
.
Conclusions/interpretation
The ability of ASC-Cme to immunomodulate HG-challenged BRECs is related to the length of time for which ASCs were preconditioned in HG medium. Conditioned medium from ASCs that had been chronically exposed to HG medium was able to normalise the HG-challenged BRECs to normal glucose levels. In contrast, conditioned medium from ASCs that had been exposed to HG medium for a shorter time did not have this effect. Our results show that the manner of HG preconditioning of ASCs dictates their immunoregulatory properties and thus the potential outcome of treatment of diabetic retinopathy.</description><subject>Adipose tissue</subject><subject>Adipose Tissue - cytology</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Capillaries</subject><subject>Cattle</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic retinopathy</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>E-Selectin - metabolism</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose - pharmacology</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Inflammation</subject><subject>Intercellular adhesion molecule 1</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Monocytes</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - metabolism</subject><subject>NF-κB protein</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Paracrine signalling</subject><subject>Pericytes</subject><subject>Pericytes - cytology</subject><subject>Pericytes - drug effects</subject><subject>Retina</subject><subject>Retina - cytology</subject><subject>Retinopathy</subject><subject>Signal Transduction - drug effects</subject><subject>Stromal cells</subject><subject>Stromal Cells - cytology</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><subject>Wound Healing - drug effects</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkU2L1TAUhoMoznXGH-BGAm7cxDn5aJsuZVBHGHAzwuxK2pzem6FNaz4u3F_lXzT1ziC4OpDz5DkvvIS84_CJAzTXEYCLigHXTDVcMnhBdlxJwUAJ_ZLstjXjun64IG9ifAQAWan6NbmQwCte82pHft_m2XhqrFuXiDS5GDMyi8Ed0dKYwjKbiQ44TZGaIVET6Zj9kNziy_tauOGUMFLn6ewGpMaXX3ldA8ZID25_YPspD0XNnLd5KM41LM6Pk5lnk5Zw2qzuaDYhXUbaL0fnkQZMbjuA3i7pgJN7DnFFXo1mivj2aV6Sn1-_3N_csrsf377ffL5jq-AiMSkbMLyyWkHdG9nKVrfIG11x1Q_C4lC3WPditH3TKA0j9tIq0SgxtlUF7Sgvycezt8T9lTGmbnZxS2A8Ljl2AgooWqV5QT_8hz4uOZT0fynZgpa6KtT7Jyr3M9puDW424dQ9V1EAcQZiWfk9hn8aDt3Wd3fuuyt9d1vfHcg_T92e0Q</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Hajmousa, Ghazaleh</creator><creator>Przybyt, Ewa</creator><creator>Pfister, Frederick</creator><creator>Paredes-Juarez, Genaro A.</creator><creator>Moganti, Kondaiah</creator><creator>Busch, Stephanie</creator><creator>Kuipers, Jeroen</creator><creator>Klaassen, Ingeborg</creator><creator>van Luyn, Marja J. A.</creator><creator>Krenning, Guido</creator><creator>Hammes, Hans-Peter</creator><creator>Harmsen, Martin C.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7428-3312</orcidid></search><sort><creationdate>20181101</creationdate><title>Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells</title><author>Hajmousa, Ghazaleh ; Przybyt, Ewa ; Pfister, Frederick ; Paredes-Juarez, Genaro A. ; Moganti, Kondaiah ; Busch, Stephanie ; Kuipers, Jeroen ; Klaassen, Ingeborg ; van Luyn, Marja J. A. ; Krenning, Guido ; Hammes, Hans-Peter ; Harmsen, Martin C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p212t-3370a15d8406ba393989e178514bc2dec69e6b2fdb77480feb3d42742f95509f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue - cytology</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Capillaries</topic><topic>Cattle</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic retinopathy</topic><topic>Diabetic Retinopathy - metabolism</topic><topic>E-Selectin - metabolism</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose - pharmacology</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Immunomodulation</topic><topic>Immunoregulation</topic><topic>Inflammation</topic><topic>Intercellular adhesion molecule 1</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Monocytes</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>NF-κB protein</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Paracrine signalling</topic><topic>Pericytes</topic><topic>Pericytes - cytology</topic><topic>Pericytes - drug effects</topic><topic>Retina</topic><topic>Retina - cytology</topic><topic>Retinopathy</topic><topic>Signal Transduction - drug effects</topic><topic>Stromal cells</topic><topic>Stromal Cells - cytology</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hajmousa, Ghazaleh</creatorcontrib><creatorcontrib>Przybyt, Ewa</creatorcontrib><creatorcontrib>Pfister, Frederick</creatorcontrib><creatorcontrib>Paredes-Juarez, Genaro A.</creatorcontrib><creatorcontrib>Moganti, Kondaiah</creatorcontrib><creatorcontrib>Busch, Stephanie</creatorcontrib><creatorcontrib>Kuipers, Jeroen</creatorcontrib><creatorcontrib>Klaassen, Ingeborg</creatorcontrib><creatorcontrib>van Luyn, Marja J. A.</creatorcontrib><creatorcontrib>Krenning, Guido</creatorcontrib><creatorcontrib>Hammes, Hans-Peter</creatorcontrib><creatorcontrib>Harmsen, Martin C.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hajmousa, Ghazaleh</au><au>Przybyt, Ewa</au><au>Pfister, Frederick</au><au>Paredes-Juarez, Genaro A.</au><au>Moganti, Kondaiah</au><au>Busch, Stephanie</au><au>Kuipers, Jeroen</au><au>Klaassen, Ingeborg</au><au>van Luyn, Marja J. A.</au><au>Krenning, Guido</au><au>Hammes, Hans-Peter</au><au>Harmsen, Martin C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>61</volume><issue>11</issue><spage>2371</spage><epage>2385</epage><pages>2371-2385</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequent aberrant angiogenesis.
Methods
We investigated the pericytic function of ASCs after intravitreal injection of ASCs in mice with retinopathy of prematurity as a model for clinical diabetic retinopathy. In addition, ASCs influence their environment by paracrine signalling. For this, we assessed the immunomodulatory capacity of conditioned medium from cultured ASCs (ASC-Cme) on high glucose (HG)-stimulated bovine retinal endothelial cells (BRECs).
Results
ASCs augmented and stabilised retinal angiogenesis and co-localised with capillaries at a pericyte-specific position. This indicates that cultured ASCs exert juxtacrine signalling in retinal microvessels. ASC-Cme alleviated HG-induced oxidative stress and its subsequent upregulation of downstream targets in an NF-κB dependent fashion in cultured BRECs. Functionally, monocyte adhesion to the monolayers of activated BRECs was also decreased by treatment with ASC-Cme and correlated with a decline in expression of adhesion-related genes such as
SELE
,
ICAM1
and
VCAM1
.
Conclusions/interpretation
The ability of ASC-Cme to immunomodulate HG-challenged BRECs is related to the length of time for which ASCs were preconditioned in HG medium. Conditioned medium from ASCs that had been chronically exposed to HG medium was able to normalise the HG-challenged BRECs to normal glucose levels. In contrast, conditioned medium from ASCs that had been exposed to HG medium for a shorter time did not have this effect. Our results show that the manner of HG preconditioning of ASCs dictates their immunoregulatory properties and thus the potential outcome of treatment of diabetic retinopathy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30151615</pmid><doi>10.1007/s00125-018-4713-0</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-7428-3312</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetologia, 2018-11, Vol.61 (11), p.2371-2385 |
| issn | 0012-186X 1432-0428 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adipose tissue Adipose Tissue - cytology Angiogenesis Animals Capillaries Cattle Cell Adhesion - drug effects Cell Survival - drug effects Cells, Cultured Diabetes Diabetes mellitus Diabetic retinopathy Diabetic Retinopathy - metabolism E-Selectin - metabolism Endothelial cells Endothelial Cells - drug effects Endothelial Cells - metabolism Enzyme-Linked Immunosorbent Assay Female Glucose Glucose - pharmacology Human Physiology Humans Immunomodulation Immunoregulation Inflammation Intercellular adhesion molecule 1 Intercellular Adhesion Molecule-1 - metabolism Internal Medicine Male Medicine Medicine & Public Health Metabolic Diseases Mice Mice, Inbred C57BL Monocytes Monocytes - drug effects Monocytes - metabolism NF-κB protein Oxidative stress Oxidative Stress - drug effects Paracrine signalling Pericytes Pericytes - cytology Pericytes - drug effects Retina Retina - cytology Retinopathy Signal Transduction - drug effects Stromal cells Stromal Cells - cytology Vascular Cell Adhesion Molecule-1 - metabolism Wound Healing - drug effects |
| title | Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells |
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