Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats
We test the hypothesis that ultrasound-targeted microbubble destruction (UTMD) technique increases the renoprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in diabetic nephropathy (DN) rats. Diabetes was induced by streptozotocin injection...
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| Veröffentlicht in: | BioMed research international 2013-01, Vol.2013 (2013), p.1-13 |
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| creator | Li, Peijing Yang, Dan Liu, Zheng Zhuo, Zhongxiong Tan, Kaibin Gao, Yunhua Wang, Gong Ye, Chuan Zhang, Yi Xia, Hongmei |
| description | We test the hypothesis that ultrasound-targeted microbubble destruction (UTMD) technique increases the renoprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in diabetic nephropathy (DN) rats. Diabetes was induced by streptozotocin injection (60 mg/Kg, intraperitoneally) in Sprague-Dawley rats. MSCs were administered alone or in combination with UTMD to DN rats at 4 weeks after diabetes onset. Random blood glucose concentrations were measured at 1, 2, 4, and 8 weeks, and plasma insulin levels, urinary albumin excretion rate (UAER) values, the structures of pancreas and kidney, the expressions of TGF-β1, synaptopodin, and IL-10 were assessed at 8 weeks after MSCs transplantation. MSCs transplantation decreased blood glucose concentrations and attenuated pancreatic islets/β cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD, which enhanced homing and retention of MSCs to kidneys. MSCs transplantation together with UTMD prevented renal damage and decreased UAER values by inhibiting TGF-β1 expression and upregulating synaptopodin and IL-10 expression. We conclude that MSCs transplantation reverts hyperglycemia; UTMD technique noninvasively increases the homing of MSCs to kidneys and promotes renal repair in DN rats. This noninvasive cell delivery method may be feasible and efficient as a novel approach for personal MSCs therapy to diabetic nephropathy. |
| doi_str_mv | 10.1155/2013/526367 |
| format | Article |
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Diabetes was induced by streptozotocin injection (60 mg/Kg, intraperitoneally) in Sprague-Dawley rats. MSCs were administered alone or in combination with UTMD to DN rats at 4 weeks after diabetes onset. Random blood glucose concentrations were measured at 1, 2, 4, and 8 weeks, and plasma insulin levels, urinary albumin excretion rate (UAER) values, the structures of pancreas and kidney, the expressions of TGF-β1, synaptopodin, and IL-10 were assessed at 8 weeks after MSCs transplantation. MSCs transplantation decreased blood glucose concentrations and attenuated pancreatic islets/β cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD, which enhanced homing and retention of MSCs to kidneys. MSCs transplantation together with UTMD prevented renal damage and decreased UAER values by inhibiting TGF-β1 expression and upregulating synaptopodin and IL-10 expression. We conclude that MSCs transplantation reverts hyperglycemia; UTMD technique noninvasively increases the homing of MSCs to kidneys and promotes renal repair in DN rats. This noninvasive cell delivery method may be feasible and efficient as a novel approach for personal MSCs therapy to diabetic nephropathy.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2013/526367</identifier><identifier>PMID: 23762850</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Animals ; Blood Glucose - metabolism ; Blotting, Western ; Bone Marrow Cells - cytology ; Capillary Permeability ; Care and treatment ; Cells, Cultured ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - genetics ; Diabetes Mellitus, Experimental - pathology ; Diabetes Mellitus, Experimental - therapy ; Diabetic nephropathies ; Diabetic Nephropathies - blood ; Diabetic Nephropathies - genetics ; Diabetic Nephropathies - pathology ; Diabetic Nephropathies - therapy ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation ; Immunohistochemistry ; Insulin - blood ; Kidney - pathology ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - cytology ; Microbubbles ; Pancreas - pathology ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Staining and Labeling ; Stem cells ; Surgery ; Transplantation ; Ultrasonics ; Urinary organs ; Vascular Cell Adhesion Molecule-1 - genetics ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>BioMed research international, 2013-01, Vol.2013 (2013), p.1-13</ispartof><rights>Copyright © 2013 Yi Zhang et al.</rights><rights>COPYRIGHT 2013 John Wiley & Sons, Inc.</rights><rights>Copyright © 2013 Yi Zhang et al. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-1797f5903b9447c27b343cd6edc5014ae98780fd0d1a89ace8c4f3899dd536e53</citedby><cites>FETCH-LOGICAL-c533t-1797f5903b9447c27b343cd6edc5014ae98780fd0d1a89ace8c4f3899dd536e53</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/PMC3677660/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677660/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23762850$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Isobe, Ken-ichi</contributor><creatorcontrib>Li, Peijing</creatorcontrib><creatorcontrib>Yang, Dan</creatorcontrib><creatorcontrib>Liu, Zheng</creatorcontrib><creatorcontrib>Zhuo, Zhongxiong</creatorcontrib><creatorcontrib>Tan, Kaibin</creatorcontrib><creatorcontrib>Gao, Yunhua</creatorcontrib><creatorcontrib>Wang, Gong</creatorcontrib><creatorcontrib>Ye, Chuan</creatorcontrib><creatorcontrib>Zhang, Yi</creatorcontrib><creatorcontrib>Xia, Hongmei</creatorcontrib><title>Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>We test the hypothesis that ultrasound-targeted microbubble destruction (UTMD) technique increases the renoprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in diabetic nephropathy (DN) rats. Diabetes was induced by streptozotocin injection (60 mg/Kg, intraperitoneally) in Sprague-Dawley rats. MSCs were administered alone or in combination with UTMD to DN rats at 4 weeks after diabetes onset. Random blood glucose concentrations were measured at 1, 2, 4, and 8 weeks, and plasma insulin levels, urinary albumin excretion rate (UAER) values, the structures of pancreas and kidney, the expressions of TGF-β1, synaptopodin, and IL-10 were assessed at 8 weeks after MSCs transplantation. MSCs transplantation decreased blood glucose concentrations and attenuated pancreatic islets/β cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD, which enhanced homing and retention of MSCs to kidneys. MSCs transplantation together with UTMD prevented renal damage and decreased UAER values by inhibiting TGF-β1 expression and upregulating synaptopodin and IL-10 expression. We conclude that MSCs transplantation reverts hyperglycemia; UTMD technique noninvasively increases the homing of MSCs to kidneys and promotes renal repair in DN rats. This noninvasive cell delivery method may be feasible and efficient as a novel approach for personal MSCs therapy to diabetic nephropathy.</description><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Blotting, Western</subject><subject>Bone Marrow Cells - cytology</subject><subject>Capillary Permeability</subject><subject>Care and treatment</subject><subject>Cells, Cultured</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - genetics</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetes Mellitus, Experimental - therapy</subject><subject>Diabetic nephropathies</subject><subject>Diabetic Nephropathies - blood</subject><subject>Diabetic Nephropathies - genetics</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic Nephropathies - therapy</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Gene Expression Regulation</subject><subject>Immunohistochemistry</subject><subject>Insulin - blood</subject><subject>Kidney - pathology</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Microbubbles</subject><subject>Pancreas - pathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Staining and Labeling</subject><subject>Stem cells</subject><subject>Surgery</subject><subject>Transplantation</subject><subject>Ultrasonics</subject><subject>Urinary organs</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><recordid>eNqNkU9vFCEYhydGY5vak3dD4sVoxsIwwHAxabb-i60a3Z4Jw7yzi5mBKTCa_S5-WFmnrvUmF0jeh4eX91cUjwl-SQhjZxUm9IxVnHJxrziuKKlLTmpy_3Cm9Kg4jfEbzqshHEv-sDiqqOBVw_Bx8fOD7RzsyrUOG0jQoXXQLk6Ddkkn6x3yPbqCCM5sd6Me0NcEI1rBMETU7tD1kIKOfnbdX8GVNcG3c9sOgC4gpjCb36LPwY8-QUTLi-gLTNoGZB26sLqFZA36CNM2-EmnbS7rFB8VD3o9RDi93U-K6zev16t35eWnt-9X55elYZSmkggpeiYxbWVdC1OJltbUdBw6wzCpNchGNLjvcEd0I7WBxtQ9baTsOkY5MHpSvFq809yO-Ra4_K1BTcGOOuyU11b9W3F2qzb-u8pTF5zjLHh2Kwj-Zs6fVqONJk9JO_BzVCSDjRAVbzL6dEE3egBlXe-z0exxdU4FpaKSssrUi4XKs4wxQH9ohmC1D17tg1dL8Jl-crf_A_sn5gw8X4CtdZ3-Yf_PBhmBXt-Bcc1ITX8BgFjB6A</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Li, Peijing</creator><creator>Yang, Dan</creator><creator>Liu, Zheng</creator><creator>Zhuo, Zhongxiong</creator><creator>Tan, Kaibin</creator><creator>Gao, Yunhua</creator><creator>Wang, Gong</creator><creator>Ye, Chuan</creator><creator>Zhang, Yi</creator><creator>Xia, Hongmei</creator><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130101</creationdate><title>Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats</title><author>Li, Peijing ; Yang, Dan ; Liu, Zheng ; Zhuo, Zhongxiong ; Tan, Kaibin ; Gao, Yunhua ; Wang, Gong ; Ye, Chuan ; Zhang, Yi ; Xia, Hongmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-1797f5903b9447c27b343cd6edc5014ae98780fd0d1a89ace8c4f3899dd536e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Blood Glucose - metabolism</topic><topic>Blotting, Western</topic><topic>Bone Marrow Cells - cytology</topic><topic>Capillary Permeability</topic><topic>Care and treatment</topic><topic>Cells, Cultured</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - genetics</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetes Mellitus, Experimental - therapy</topic><topic>Diabetic nephropathies</topic><topic>Diabetic Nephropathies - blood</topic><topic>Diabetic Nephropathies - genetics</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic Nephropathies - therapy</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Gene Expression Regulation</topic><topic>Immunohistochemistry</topic><topic>Insulin - blood</topic><topic>Kidney - pathology</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Microbubbles</topic><topic>Pancreas - pathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Staining and Labeling</topic><topic>Stem cells</topic><topic>Surgery</topic><topic>Transplantation</topic><topic>Ultrasonics</topic><topic>Urinary organs</topic><topic>Vascular Cell Adhesion Molecule-1 - genetics</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Peijing</creatorcontrib><creatorcontrib>Yang, Dan</creatorcontrib><creatorcontrib>Liu, Zheng</creatorcontrib><creatorcontrib>Zhuo, Zhongxiong</creatorcontrib><creatorcontrib>Tan, Kaibin</creatorcontrib><creatorcontrib>Gao, Yunhua</creatorcontrib><creatorcontrib>Wang, Gong</creatorcontrib><creatorcontrib>Ye, Chuan</creatorcontrib><creatorcontrib>Zhang, Yi</creatorcontrib><creatorcontrib>Xia, Hongmei</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Peijing</au><au>Yang, Dan</au><au>Liu, Zheng</au><au>Zhuo, Zhongxiong</au><au>Tan, Kaibin</au><au>Gao, Yunhua</au><au>Wang, Gong</au><au>Ye, Chuan</au><au>Zhang, Yi</au><au>Xia, Hongmei</au><au>Isobe, Ken-ichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>2013</volume><issue>2013</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>We test the hypothesis that ultrasound-targeted microbubble destruction (UTMD) technique increases the renoprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in diabetic nephropathy (DN) rats. Diabetes was induced by streptozotocin injection (60 mg/Kg, intraperitoneally) in Sprague-Dawley rats. MSCs were administered alone or in combination with UTMD to DN rats at 4 weeks after diabetes onset. Random blood glucose concentrations were measured at 1, 2, 4, and 8 weeks, and plasma insulin levels, urinary albumin excretion rate (UAER) values, the structures of pancreas and kidney, the expressions of TGF-β1, synaptopodin, and IL-10 were assessed at 8 weeks after MSCs transplantation. MSCs transplantation decreased blood glucose concentrations and attenuated pancreatic islets/β cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD, which enhanced homing and retention of MSCs to kidneys. MSCs transplantation together with UTMD prevented renal damage and decreased UAER values by inhibiting TGF-β1 expression and upregulating synaptopodin and IL-10 expression. We conclude that MSCs transplantation reverts hyperglycemia; UTMD technique noninvasively increases the homing of MSCs to kidneys and promotes renal repair in DN rats. This noninvasive cell delivery method may be feasible and efficient as a novel approach for personal MSCs therapy to diabetic nephropathy.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>23762850</pmid><doi>10.1155/2013/526367</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blood Glucose - metabolism Blotting, Western Bone Marrow Cells - cytology Capillary Permeability Care and treatment Cells, Cultured Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - pathology Diabetes Mellitus, Experimental - therapy Diabetic nephropathies Diabetic Nephropathies - blood Diabetic Nephropathies - genetics Diabetic Nephropathies - pathology Diabetic Nephropathies - therapy Enzyme-Linked Immunosorbent Assay Gene Expression Regulation Immunohistochemistry Insulin - blood Kidney - pathology Male Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells - cytology Microbubbles Pancreas - pathology Rats Rats, Sprague-Dawley RNA, Messenger - genetics RNA, Messenger - metabolism Staining and Labeling Stem cells Surgery Transplantation Ultrasonics Urinary organs Vascular Cell Adhesion Molecule-1 - genetics Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats |
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