Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease
ABSTRACT The current study is based on the hypothesis of mesenchymal stromal cells (MSCs) contributing to soft‐tissue calcification and ectopic osteogenesis in chronic kidney disease (CKD). Rat MSCs were transplanted intraperitoneally in an established three‐dimensional collagen‐based model in healt...
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| Veröffentlicht in: | Journal of bone and mineral research 2013-12, Vol.28 (12), p.2523-2534 |
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| container_title | Journal of bone and mineral research |
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| creator | Kramann, Rafael Kunter, Uta Brandenburg, Vincent M Leisten, Isabelle Ehling, Josef Klinkhammer, Barbara M Knüchel, Ruth Floege, Jürgen Schneider, Rebekka K |
| description | ABSTRACT
The current study is based on the hypothesis of mesenchymal stromal cells (MSCs) contributing to soft‐tissue calcification and ectopic osteogenesis in chronic kidney disease (CKD). Rat MSCs were transplanted intraperitoneally in an established three‐dimensional collagen‐based model in healthy control animals and two rat models of CKD and vascular calcification: (1) 5/6 nephrectomy + high phosphorus diet; and (2) adenine nephropathy. As internal controls, collagen gels without MSCs were transplanted in the same animals. After 4 and 8 weeks, MSCs were still detectable and proliferating in the collagen gels (fluorescence‐activated cell sorting [FACS] analysis and confocal microscopy after fluorescence labeling of the cells). Aortas and MSC‐containing collagen gels in CKD animals showed distinct similarities in calcification (micro–computed tomography [µCT], energy‐dispersive X‐ray [EDX] analysis, calcium content), induction of osteogenic markers, (ie, bone morphogenic protein 2 [BMP‐2], Runt related transcription factor 2 [Runx2], alkaline phosphatase [ALP]), upregulation of the osteocytic marker sclerostin and extracellular matrix remodeling with increased expression of osteopontin, collagen I/III/IV, fibronectin, and laminin. Calcification, osteogenesis, and matrix remodeling were never observed in healthy control animals and non‐MSC–containing collagen gels in all groups. Paul Karl Horan 26 (PKH‐26)‐labeled, 3G5‐positive MSCs expressed Runx2 and sclerostin in CKD animals whereas PKH‐26‐negative migrated cells did not express osteogenic markers. In conclusion, heterotopically implanted MSCs undergo osteogenic differentiation in rat models of CKD‐induced vascular calcification, supporting our hypothesis of MSCs as possible players in heterotopic calcification processes of CKD patients. © 2013 American Society for Bone and Mineral Research. |
| doi_str_mv | 10.1002/jbmr.1994 |
| format | Article |
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The current study is based on the hypothesis of mesenchymal stromal cells (MSCs) contributing to soft‐tissue calcification and ectopic osteogenesis in chronic kidney disease (CKD). Rat MSCs were transplanted intraperitoneally in an established three‐dimensional collagen‐based model in healthy control animals and two rat models of CKD and vascular calcification: (1) 5/6 nephrectomy + high phosphorus diet; and (2) adenine nephropathy. As internal controls, collagen gels without MSCs were transplanted in the same animals. After 4 and 8 weeks, MSCs were still detectable and proliferating in the collagen gels (fluorescence‐activated cell sorting [FACS] analysis and confocal microscopy after fluorescence labeling of the cells). Aortas and MSC‐containing collagen gels in CKD animals showed distinct similarities in calcification (micro–computed tomography [µCT], energy‐dispersive X‐ray [EDX] analysis, calcium content), induction of osteogenic markers, (ie, bone morphogenic protein 2 [BMP‐2], Runt related transcription factor 2 [Runx2], alkaline phosphatase [ALP]), upregulation of the osteocytic marker sclerostin and extracellular matrix remodeling with increased expression of osteopontin, collagen I/III/IV, fibronectin, and laminin. Calcification, osteogenesis, and matrix remodeling were never observed in healthy control animals and non‐MSC–containing collagen gels in all groups. Paul Karl Horan 26 (PKH‐26)‐labeled, 3G5‐positive MSCs expressed Runx2 and sclerostin in CKD animals whereas PKH‐26‐negative migrated cells did not express osteogenic markers. In conclusion, heterotopically implanted MSCs undergo osteogenic differentiation in rat models of CKD‐induced vascular calcification, supporting our hypothesis of MSCs as possible players in heterotopic calcification processes of CKD patients. © 2013 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.1994</identifier><identifier>PMID: 23703894</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adenine ; Animals ; Aorta - metabolism ; Biomarkers - metabolism ; Bone Morphogenetic Proteins - metabolism ; Calcification, Physiologic ; Cell Differentiation ; Cell Movement ; CHRONIC KIDNEY DISEASE ; Collagen - metabolism ; Core Binding Factor Alpha 1 Subunit - metabolism ; Disease Models, Animal ; Extracellular Matrix - metabolism ; Gels ; Gene Expression Regulation ; Genetic Markers ; Kidney Function Tests ; Male ; MATRIX REMODELING ; Mesenchymal Stem Cell Transplantation ; MESENCHYMAL STROMAL CELLS ; Mesenchymal Stromal Cells - cytology ; Nephrectomy ; Organic Chemicals - metabolism ; OSTEOGENESIS ; Pericytes - metabolism ; Rats ; Renal Insufficiency, Chronic - physiopathology ; Renal Insufficiency, Chronic - therapy ; Transplantation, Heterotopic ; Up-Regulation ; VASCULAR CALCIFICATION</subject><ispartof>Journal of bone and mineral research, 2013-12, Vol.28 (12), p.2523-2534</ispartof><rights>2013 American Society for Bone and Mineral Research</rights><rights>2013 American Society for Bone and Mineral Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4874-ff067fca1e675217d193afd14153ccebab7e5160615bb9733f83dedcb8f55e603</citedby><cites>FETCH-LOGICAL-c4874-ff067fca1e675217d193afd14153ccebab7e5160615bb9733f83dedcb8f55e603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.1994$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.1994$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23703894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kramann, Rafael</creatorcontrib><creatorcontrib>Kunter, Uta</creatorcontrib><creatorcontrib>Brandenburg, Vincent M</creatorcontrib><creatorcontrib>Leisten, Isabelle</creatorcontrib><creatorcontrib>Ehling, Josef</creatorcontrib><creatorcontrib>Klinkhammer, Barbara M</creatorcontrib><creatorcontrib>Knüchel, Ruth</creatorcontrib><creatorcontrib>Floege, Jürgen</creatorcontrib><creatorcontrib>Schneider, Rebekka K</creatorcontrib><title>Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT
The current study is based on the hypothesis of mesenchymal stromal cells (MSCs) contributing to soft‐tissue calcification and ectopic osteogenesis in chronic kidney disease (CKD). Rat MSCs were transplanted intraperitoneally in an established three‐dimensional collagen‐based model in healthy control animals and two rat models of CKD and vascular calcification: (1) 5/6 nephrectomy + high phosphorus diet; and (2) adenine nephropathy. As internal controls, collagen gels without MSCs were transplanted in the same animals. After 4 and 8 weeks, MSCs were still detectable and proliferating in the collagen gels (fluorescence‐activated cell sorting [FACS] analysis and confocal microscopy after fluorescence labeling of the cells). Aortas and MSC‐containing collagen gels in CKD animals showed distinct similarities in calcification (micro–computed tomography [µCT], energy‐dispersive X‐ray [EDX] analysis, calcium content), induction of osteogenic markers, (ie, bone morphogenic protein 2 [BMP‐2], Runt related transcription factor 2 [Runx2], alkaline phosphatase [ALP]), upregulation of the osteocytic marker sclerostin and extracellular matrix remodeling with increased expression of osteopontin, collagen I/III/IV, fibronectin, and laminin. Calcification, osteogenesis, and matrix remodeling were never observed in healthy control animals and non‐MSC–containing collagen gels in all groups. Paul Karl Horan 26 (PKH‐26)‐labeled, 3G5‐positive MSCs expressed Runx2 and sclerostin in CKD animals whereas PKH‐26‐negative migrated cells did not express osteogenic markers. In conclusion, heterotopically implanted MSCs undergo osteogenic differentiation in rat models of CKD‐induced vascular calcification, supporting our hypothesis of MSCs as possible players in heterotopic calcification processes of CKD patients. © 2013 American Society for Bone and Mineral Research.</description><subject>Adenine</subject><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>Biomarkers - metabolism</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Calcification, Physiologic</subject><subject>Cell Differentiation</subject><subject>Cell Movement</subject><subject>CHRONIC KIDNEY DISEASE</subject><subject>Collagen - metabolism</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>Disease Models, Animal</subject><subject>Extracellular Matrix - metabolism</subject><subject>Gels</subject><subject>Gene Expression Regulation</subject><subject>Genetic Markers</subject><subject>Kidney Function Tests</subject><subject>Male</subject><subject>MATRIX REMODELING</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>MESENCHYMAL STROMAL CELLS</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Nephrectomy</subject><subject>Organic Chemicals - metabolism</subject><subject>OSTEOGENESIS</subject><subject>Pericytes - metabolism</subject><subject>Rats</subject><subject>Renal Insufficiency, Chronic - physiopathology</subject><subject>Renal Insufficiency, Chronic - therapy</subject><subject>Transplantation, Heterotopic</subject><subject>Up-Regulation</subject><subject>VASCULAR CALCIFICATION</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0Utv1DAUhmELgehQWPAHkCU2sEjrE1-zhOFSoKNKpawjxzmmHiX2YGeE8u_JdAoLJMTqbB69svUR8hzYGTBWn2-7MZ9B04gHZAWy5pVQBh6SFTNGVExwOCFPStkyxpRU6jE5qblm3DRiReJVmTB9x4glFJo8vcAJc5rSLjg7DDO9yTaW3WDjhD3dYMHobufRDvTrlNPhrnEYCg2RXtuJblKPw11nfZtTDI5-CX3Emb4LBW3Bp-SRt0PBZ_f3lHz78P5mfVFdXn38tH5zWTlhtKi8Z0p7ZwGVljXoHhpufQ8CJHcOO9tplKCYAtl1jebcG95j7zrjpUTF-Cl5dezucvqxxzK1YyhueamNmPalBcmY1k1Ty_9ToYBzo5hZ6Mu_6Dbtc1w-sijZCKi5gUW9PiqXUykZfbvLYbR5boG1h73aw17tYa_Fvrgv7rsR-z_y90ALOD-Cn2HA-d-l9vPbzfVd8hck_Z_g</recordid><startdate>201312</startdate><enddate>201312</enddate><creator>Kramann, Rafael</creator><creator>Kunter, Uta</creator><creator>Brandenburg, Vincent M</creator><creator>Leisten, Isabelle</creator><creator>Ehling, Josef</creator><creator>Klinkhammer, Barbara M</creator><creator>Knüchel, Ruth</creator><creator>Floege, Jürgen</creator><creator>Schneider, Rebekka K</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7TS</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201312</creationdate><title>Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease</title><author>Kramann, Rafael ; Kunter, Uta ; Brandenburg, Vincent M ; Leisten, Isabelle ; Ehling, Josef ; Klinkhammer, Barbara M ; Knüchel, Ruth ; Floege, Jürgen ; Schneider, Rebekka K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4874-ff067fca1e675217d193afd14153ccebab7e5160615bb9733f83dedcb8f55e603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenine</topic><topic>Animals</topic><topic>Aorta - metabolism</topic><topic>Biomarkers - metabolism</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>Calcification, Physiologic</topic><topic>Cell Differentiation</topic><topic>Cell Movement</topic><topic>CHRONIC KIDNEY DISEASE</topic><topic>Collagen - metabolism</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>Disease Models, Animal</topic><topic>Extracellular Matrix - metabolism</topic><topic>Gels</topic><topic>Gene Expression Regulation</topic><topic>Genetic Markers</topic><topic>Kidney Function Tests</topic><topic>Male</topic><topic>MATRIX REMODELING</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>MESENCHYMAL STROMAL CELLS</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Nephrectomy</topic><topic>Organic Chemicals - metabolism</topic><topic>OSTEOGENESIS</topic><topic>Pericytes - metabolism</topic><topic>Rats</topic><topic>Renal Insufficiency, Chronic - physiopathology</topic><topic>Renal Insufficiency, Chronic - therapy</topic><topic>Transplantation, Heterotopic</topic><topic>Up-Regulation</topic><topic>VASCULAR CALCIFICATION</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kramann, Rafael</creatorcontrib><creatorcontrib>Kunter, Uta</creatorcontrib><creatorcontrib>Brandenburg, Vincent M</creatorcontrib><creatorcontrib>Leisten, Isabelle</creatorcontrib><creatorcontrib>Ehling, Josef</creatorcontrib><creatorcontrib>Klinkhammer, Barbara M</creatorcontrib><creatorcontrib>Knüchel, Ruth</creatorcontrib><creatorcontrib>Floege, Jürgen</creatorcontrib><creatorcontrib>Schneider, Rebekka K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kramann, Rafael</au><au>Kunter, Uta</au><au>Brandenburg, Vincent M</au><au>Leisten, Isabelle</au><au>Ehling, Josef</au><au>Klinkhammer, Barbara M</au><au>Knüchel, Ruth</au><au>Floege, Jürgen</au><au>Schneider, Rebekka K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2013-12</date><risdate>2013</risdate><volume>28</volume><issue>12</issue><spage>2523</spage><epage>2534</epage><pages>2523-2534</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>ABSTRACT
The current study is based on the hypothesis of mesenchymal stromal cells (MSCs) contributing to soft‐tissue calcification and ectopic osteogenesis in chronic kidney disease (CKD). Rat MSCs were transplanted intraperitoneally in an established three‐dimensional collagen‐based model in healthy control animals and two rat models of CKD and vascular calcification: (1) 5/6 nephrectomy + high phosphorus diet; and (2) adenine nephropathy. As internal controls, collagen gels without MSCs were transplanted in the same animals. After 4 and 8 weeks, MSCs were still detectable and proliferating in the collagen gels (fluorescence‐activated cell sorting [FACS] analysis and confocal microscopy after fluorescence labeling of the cells). Aortas and MSC‐containing collagen gels in CKD animals showed distinct similarities in calcification (micro–computed tomography [µCT], energy‐dispersive X‐ray [EDX] analysis, calcium content), induction of osteogenic markers, (ie, bone morphogenic protein 2 [BMP‐2], Runt related transcription factor 2 [Runx2], alkaline phosphatase [ALP]), upregulation of the osteocytic marker sclerostin and extracellular matrix remodeling with increased expression of osteopontin, collagen I/III/IV, fibronectin, and laminin. Calcification, osteogenesis, and matrix remodeling were never observed in healthy control animals and non‐MSC–containing collagen gels in all groups. Paul Karl Horan 26 (PKH‐26)‐labeled, 3G5‐positive MSCs expressed Runx2 and sclerostin in CKD animals whereas PKH‐26‐negative migrated cells did not express osteogenic markers. In conclusion, heterotopically implanted MSCs undergo osteogenic differentiation in rat models of CKD‐induced vascular calcification, supporting our hypothesis of MSCs as possible players in heterotopic calcification processes of CKD patients. © 2013 American Society for Bone and Mineral Research.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23703894</pmid><doi>10.1002/jbmr.1994</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Adenine Animals Aorta - metabolism Biomarkers - metabolism Bone Morphogenetic Proteins - metabolism Calcification, Physiologic Cell Differentiation Cell Movement CHRONIC KIDNEY DISEASE Collagen - metabolism Core Binding Factor Alpha 1 Subunit - metabolism Disease Models, Animal Extracellular Matrix - metabolism Gels Gene Expression Regulation Genetic Markers Kidney Function Tests Male MATRIX REMODELING Mesenchymal Stem Cell Transplantation MESENCHYMAL STROMAL CELLS Mesenchymal Stromal Cells - cytology Nephrectomy Organic Chemicals - metabolism OSTEOGENESIS Pericytes - metabolism Rats Renal Insufficiency, Chronic - physiopathology Renal Insufficiency, Chronic - therapy Transplantation, Heterotopic Up-Regulation VASCULAR CALCIFICATION |
| title | Osteogenesis of Heterotopically Transplanted Mesenchymal Stromal Cells in Rat Models of Chronic Kidney Disease |
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