Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats
The present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Da...
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description | The present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Dawley rats through the tail vein at the following different time points after thorax irradiation: two hours, seven days, and two hours + seven days. Post Ad-MSCs transplantation and the histopathological analysis of the lungs were performed along with analysis of inflammatory cytokine levels, including interleukin (IL)-1, IL-2, IL-6, IL-10 and tumor necrosis factor-α (TNF-α). In particular, pro-fibrotic factors (TGF-β1 and α-SMA) were also evaluated in serum and lung tissues. In addition, it was also determined whether Ad-MSCs had any role in inhibiting the transition of type II alveolar epithelial cells into fibroblasts in the lungs of injured rats. The present results demonstrated that the intravenous delivery of Ad-MSCs twice at the 2-hour and 7-day (R + MSC
2h+7d
group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC
2h+7d
group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC
2h+7d
group) exhibited significantly reduced TGF-β1 and α-SMA levels, in contrast to rats in the R + MSC
7d
or R + MSC
2h
groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC
2h
and R + MSC
2h+7d
groups. The present study concluded that two injections of Ad-MSCs (R + MSC
2h+7d
group) appear to be optimal for therapeutic efficacy and safety during RILF. |
doi_str_mv | 10.1038/s41598-019-41576-5 |
format | Article |
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2h+7d
group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC
2h+7d
group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC
2h+7d
group) exhibited significantly reduced TGF-β1 and α-SMA levels, in contrast to rats in the R + MSC
7d
or R + MSC
2h
groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC
2h
and R + MSC
2h+7d
groups. The present study concluded that two injections of Ad-MSCs (R + MSC
2h+7d
group) appear to be optimal for therapeutic efficacy and safety during RILF.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-41576-5</identifier><identifier>PMID: 30944348</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/100 ; 631/532/2074 ; 692/699/1785/4039 ; 82 ; 82/51 ; Adipose Tissue - metabolism ; Adipose Tissue - pathology ; Adiposity - physiology ; Alveoli ; Animals ; Cells, Cultured ; Cytokines ; Cytokines - metabolism ; Disease Models, Animal ; Epithelial cells ; Fibroblasts ; Fibrosis ; Humanities and Social Sciences ; Inflammation ; Interleukin 1 ; Interleukin 10 ; Interleukin 2 ; Interleukin 6 ; Intravenous administration ; Irradiation ; Lung - metabolism ; Lung - pathology ; Lungs ; Male ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; multidisciplinary ; Pulmonary Fibrosis - metabolism ; Pulmonary Fibrosis - pathology ; Radiation ; Radiation Injuries - metabolism ; Radiation Injuries - pathology ; Radiation Pneumonitis - metabolism ; Radiation Pneumonitis - pathology ; Rats ; Rats, Sprague-Dawley ; Rodents ; Science ; Science (multidisciplinary) ; Serum levels ; Stem cells ; Transforming growth factor-b1 ; Transplantation ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>Scientific reports, 2019-04, Vol.9 (1), p.5589, Article 5589</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. 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><citedby>FETCH-LOGICAL-c474t-e06b0b85577ab5fcb591e26b433f8a450215405e14e533a419f3b4af6a171e573</citedby><cites>FETCH-LOGICAL-c474t-e06b0b85577ab5fcb591e26b433f8a450215405e14e533a419f3b4af6a171e573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447528/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447528/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30944348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Jiang, Xinping</creatorcontrib><creatorcontrib>Ren, Liqun</creatorcontrib><title>Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Dawley rats through the tail vein at the following different time points after thorax irradiation: two hours, seven days, and two hours + seven days. Post Ad-MSCs transplantation and the histopathological analysis of the lungs were performed along with analysis of inflammatory cytokine levels, including interleukin (IL)-1, IL-2, IL-6, IL-10 and tumor necrosis factor-α (TNF-α). In particular, pro-fibrotic factors (TGF-β1 and α-SMA) were also evaluated in serum and lung tissues. In addition, it was also determined whether Ad-MSCs had any role in inhibiting the transition of type II alveolar epithelial cells into fibroblasts in the lungs of injured rats. The present results demonstrated that the intravenous delivery of Ad-MSCs twice at the 2-hour and 7-day (R + MSC
2h+7d
group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC
2h+7d
group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC
2h+7d
group) exhibited significantly reduced TGF-β1 and α-SMA levels, in contrast to rats in the R + MSC
7d
or R + MSC
2h
groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC
2h
and R + MSC
2h+7d
groups. The present study concluded that two injections of Ad-MSCs (R + MSC
2h+7d
group) appear to be optimal for therapeutic efficacy and safety during RILF.</description><subject>13</subject><subject>13/100</subject><subject>631/532/2074</subject><subject>692/699/1785/4039</subject><subject>82</subject><subject>82/51</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose Tissue - pathology</subject><subject>Adiposity - physiology</subject><subject>Alveoli</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Epithelial cells</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Humanities and Social Sciences</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin 10</subject><subject>Interleukin 2</subject><subject>Interleukin 6</subject><subject>Intravenous administration</subject><subject>Irradiation</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lungs</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchyme</subject><subject>multidisciplinary</subject><subject>Pulmonary Fibrosis - metabolism</subject><subject>Pulmonary Fibrosis - pathology</subject><subject>Radiation</subject><subject>Radiation Injuries - metabolism</subject><subject>Radiation Injuries - pathology</subject><subject>Radiation Pneumonitis - metabolism</subject><subject>Radiation Pneumonitis - pathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Serum levels</subject><subject>Stem cells</subject><subject>Transforming growth factor-b1</subject><subject>Transplantation</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UUtLHTEUDkWpov6BLkqg62iek5lNoYgvENy065CZObk3MpPcJhnhCv3vjV61dmM2OfA9znf4EPrC6Cmjoj3LkqmuJZR1pE66IeoTOuRUKsIF53vv5gN0kvM9rU_xTrLuMzoQtJNSyPYQ_bnbFD_7R1t8DDg6XNaA7eg3MQMZIfkHGPEMGcKw3s52wrnAjAeYJjzCVNG0xdUAsIsJpyp8NiI-jMtQldMSVtj5PsXsMy4JbJkhFOxDJZd8jPadnTKcvPxH6Nflxc_za3J7d3Vz_uOWDFLLQoA2Pe1bpbS2vXJDrzoGvOmlEK61UlHOlKQKmAQlhK03OtFL6xrLNAOlxRH6vvPdLP0M41AjJDuZTfKzTVsTrTf_I8GvzSo-mEZKrXhbDb69GKT4e4FczH1cUqiZDeeUay2k6CqL71hDvTcncG8bGDVPrZlda6a2Zp5bM6qKvr7P9iZ57agSxI6QKxRWkP7t_sD2L88lpZ8</recordid><startdate>20190403</startdate><enddate>20190403</enddate><creator>Zhang, Yang</creator><creator>Jiang, Xinping</creator><creator>Ren, Liqun</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20190403</creationdate><title>Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats</title><author>Zhang, Yang ; Jiang, Xinping ; Ren, Liqun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-e06b0b85577ab5fcb591e26b433f8a450215405e14e533a419f3b4af6a171e573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13</topic><topic>13/100</topic><topic>631/532/2074</topic><topic>692/699/1785/4039</topic><topic>82</topic><topic>82/51</topic><topic>Adipose Tissue - metabolism</topic><topic>Adipose Tissue - pathology</topic><topic>Adiposity - physiology</topic><topic>Alveoli</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Epithelial cells</topic><topic>Fibroblasts</topic><topic>Fibrosis</topic><topic>Humanities and Social Sciences</topic><topic>Inflammation</topic><topic>Interleukin 1</topic><topic>Interleukin 10</topic><topic>Interleukin 2</topic><topic>Interleukin 6</topic><topic>Intravenous administration</topic><topic>Irradiation</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lungs</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchyme</topic><topic>multidisciplinary</topic><topic>Pulmonary Fibrosis - metabolism</topic><topic>Pulmonary Fibrosis - pathology</topic><topic>Radiation</topic><topic>Radiation Injuries - metabolism</topic><topic>Radiation Injuries - pathology</topic><topic>Radiation Pneumonitis - metabolism</topic><topic>Radiation Pneumonitis - pathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Serum levels</topic><topic>Stem cells</topic><topic>Transforming growth factor-b1</topic><topic>Transplantation</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Jiang, Xinping</creatorcontrib><creatorcontrib>Ren, Liqun</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>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yang</au><au>Jiang, Xinping</au><au>Ren, Liqun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-04-03</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>5589</spage><pages>5589-</pages><artnum>5589</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Dawley rats through the tail vein at the following different time points after thorax irradiation: two hours, seven days, and two hours + seven days. Post Ad-MSCs transplantation and the histopathological analysis of the lungs were performed along with analysis of inflammatory cytokine levels, including interleukin (IL)-1, IL-2, IL-6, IL-10 and tumor necrosis factor-α (TNF-α). In particular, pro-fibrotic factors (TGF-β1 and α-SMA) were also evaluated in serum and lung tissues. In addition, it was also determined whether Ad-MSCs had any role in inhibiting the transition of type II alveolar epithelial cells into fibroblasts in the lungs of injured rats. The present results demonstrated that the intravenous delivery of Ad-MSCs twice at the 2-hour and 7-day (R + MSC
2h+7d
group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC
2h+7d
group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC
2h+7d
group) exhibited significantly reduced TGF-β1 and α-SMA levels, in contrast to rats in the R + MSC
7d
or R + MSC
2h
groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC
2h
and R + MSC
2h+7d
groups. The present study concluded that two injections of Ad-MSCs (R + MSC
2h+7d
group) appear to be optimal for therapeutic efficacy and safety during RILF.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30944348</pmid><doi>10.1038/s41598-019-41576-5</doi><oa>free_for_read</oa></addata></record> |
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subjects | 13 13/100 631/532/2074 692/699/1785/4039 82 82/51 Adipose Tissue - metabolism Adipose Tissue - pathology Adiposity - physiology Alveoli Animals Cells, Cultured Cytokines Cytokines - metabolism Disease Models, Animal Epithelial cells Fibroblasts Fibrosis Humanities and Social Sciences Inflammation Interleukin 1 Interleukin 10 Interleukin 2 Interleukin 6 Intravenous administration Irradiation Lung - metabolism Lung - pathology Lungs Male Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - metabolism Mesenchyme multidisciplinary Pulmonary Fibrosis - metabolism Pulmonary Fibrosis - pathology Radiation Radiation Injuries - metabolism Radiation Injuries - pathology Radiation Pneumonitis - metabolism Radiation Pneumonitis - pathology Rats Rats, Sprague-Dawley Rodents Science Science (multidisciplinary) Serum levels Stem cells Transforming growth factor-b1 Transplantation Tumor necrosis factor-TNF Tumor necrosis factor-α |
title | Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats |
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