Synergistic Angiogenic Effect of Codelivering Fibroblast Growth Factor 2 and Granulocyte-Colony Stimulating Factor from Fibrin Scaffolds and Bone Marrow Transplantation in Critical Limb Ischemia
Increasing evidence suggests that therapeutic angiogenesis strategies utilizing cytokines and stem cells are necessary to treat traumatic vascular events such as critical limb ischemia and peripheral artery disease. In this study, basic fibroblast growth factor 2 (FGF-2) and granulocyte-colony stimu...
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| Veröffentlicht in: | Tissue engineering. Part A 2011-01, Vol.17 (1-2), p.243-254 |
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| creator | Layman, Hans Rahnemai-Azar, Amir A Pham, Si M. Tsechpenakis, Gavriil Andreopoulos, Fotios M. |
| description | Increasing evidence suggests that therapeutic angiogenesis strategies utilizing cytokines and stem cells are necessary to treat traumatic vascular events such as critical limb ischemia and peripheral artery disease. In this study, basic fibroblast growth factor 2 (FGF-2) and granulocyte-colony stimulating factor (G-CSF) were immobilized in fibrin matrices and codelivered in combination with unfractionated bone marrow cells. Hindlimb ischemia was induced on young (6–7 weeks) Balb/C mice, and fibrin gels containing 100 ng/mL of FGF-2 and G-CSF were implanted adjacent to the ligation points. In addition, 1 × 10
6
bone marrow (BM) cells were injected into five locations in the ischemic muscle immediately after ligation and artery excision. Hindlimb reperfusion was determined by Laser Doppler Perfusion Imaging and immunohistochemistry for CD31+ and smooth muscle actin-positive cells at 2, 4, and 8 weeks postsurgery to identify capillary formation and maturation. A fluorescent vessel painting technique was also utilized to determine the extent of angiogenesis and arteriogenesis in the hindlimb at 8 weeks postsurgery. The codelivery of FGF-2 and G-CSF in combination with BM cells led to enhanced therapeutic recovery in critical limb ischemia Balb/C mice after 8 weeks of treatment with 87.2% blood flow recovery and a significant increase (
p
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| doi_str_mv | 10.1089/ten.tea.2010.0270 |
| format | Article |
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6
bone marrow (BM) cells were injected into five locations in the ischemic muscle immediately after ligation and artery excision. Hindlimb reperfusion was determined by Laser Doppler Perfusion Imaging and immunohistochemistry for CD31+ and smooth muscle actin-positive cells at 2, 4, and 8 weeks postsurgery to identify capillary formation and maturation. A fluorescent vessel painting technique was also utilized to determine the extent of angiogenesis and arteriogenesis in the hindlimb at 8 weeks postsurgery. The codelivery of FGF-2 and G-CSF in combination with BM cells led to enhanced therapeutic recovery in critical limb ischemia Balb/C mice after 8 weeks of treatment with 87.2% blood flow recovery and a significant increase (
p
< 0.05) in capillary formation in comparison to growth factor delivery or BM cell administration alone.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2010.0270</identifier><identifier>PMID: 20712534</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animals ; Bone marrow ; Bone Marrow Cells - cytology ; Bone Marrow Cells - drug effects ; Bone Marrow Transplantation - methods ; Care and treatment ; Cattle ; Cells, Cultured ; Cytokines ; Fibroblast Growth Factor 2 - chemistry ; Fibroblast Growth Factor 2 - pharmacology ; Fibroblast growth factors ; Granulocyte colony-stimulating factor ; Granulocyte Colony-Stimulating Factor - chemistry ; Granulocyte Colony-Stimulating Factor - pharmacology ; Health aspects ; Hindlimb - pathology ; Humans ; Immunohistochemistry ; Ischemia ; Ischemia - therapy ; Male ; Mice ; Mice, Inbred BALB C ; Original Articles ; Physiological aspects ; Risk factors ; Rodents ; Stem cells ; Tissue engineering ; Tissue Scaffolds ; Transplantation</subject><ispartof>Tissue engineering. Part A, 2011-01, Vol.17 (1-2), p.243-254</ispartof><rights>2011, Mary Ann Liebert, Inc.</rights><rights>COPYRIGHT 2011 Mary Ann Liebert, Inc.</rights><rights>(©) Copyright 2011, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-37feb75a8671ba95360911c0542db487df9c218225e8b54a0ac81e9bf3be04a43</citedby><cites>FETCH-LOGICAL-c474t-37feb75a8671ba95360911c0542db487df9c218225e8b54a0ac81e9bf3be04a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20712534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Layman, Hans</creatorcontrib><creatorcontrib>Rahnemai-Azar, Amir A</creatorcontrib><creatorcontrib>Pham, Si M.</creatorcontrib><creatorcontrib>Tsechpenakis, Gavriil</creatorcontrib><creatorcontrib>Andreopoulos, Fotios M.</creatorcontrib><title>Synergistic Angiogenic Effect of Codelivering Fibroblast Growth Factor 2 and Granulocyte-Colony Stimulating Factor from Fibrin Scaffolds and Bone Marrow Transplantation in Critical Limb Ischemia</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>Increasing evidence suggests that therapeutic angiogenesis strategies utilizing cytokines and stem cells are necessary to treat traumatic vascular events such as critical limb ischemia and peripheral artery disease. In this study, basic fibroblast growth factor 2 (FGF-2) and granulocyte-colony stimulating factor (G-CSF) were immobilized in fibrin matrices and codelivered in combination with unfractionated bone marrow cells. Hindlimb ischemia was induced on young (6–7 weeks) Balb/C mice, and fibrin gels containing 100 ng/mL of FGF-2 and G-CSF were implanted adjacent to the ligation points. In addition, 1 × 10
6
bone marrow (BM) cells were injected into five locations in the ischemic muscle immediately after ligation and artery excision. Hindlimb reperfusion was determined by Laser Doppler Perfusion Imaging and immunohistochemistry for CD31+ and smooth muscle actin-positive cells at 2, 4, and 8 weeks postsurgery to identify capillary formation and maturation. A fluorescent vessel painting technique was also utilized to determine the extent of angiogenesis and arteriogenesis in the hindlimb at 8 weeks postsurgery. The codelivery of FGF-2 and G-CSF in combination with BM cells led to enhanced therapeutic recovery in critical limb ischemia Balb/C mice after 8 weeks of treatment with 87.2% blood flow recovery and a significant increase (
p
< 0.05) in capillary formation in comparison to growth factor delivery or BM cell administration alone.</description><subject>Animals</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Transplantation - methods</subject><subject>Care and treatment</subject><subject>Cattle</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Fibroblast Growth Factor 2 - chemistry</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Fibroblast growth factors</subject><subject>Granulocyte colony-stimulating factor</subject><subject>Granulocyte Colony-Stimulating Factor - chemistry</subject><subject>Granulocyte Colony-Stimulating Factor - pharmacology</subject><subject>Health aspects</subject><subject>Hindlimb - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Ischemia</subject><subject>Ischemia - therapy</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Original Articles</subject><subject>Physiological aspects</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Stem cells</subject><subject>Tissue engineering</subject><subject>Tissue Scaffolds</subject><subject>Transplantation</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNksFu1DAQhiMEoqXwAFyQBQdOWWzHiZPjsuqWSos4bJG4RbYz3rpy7MV2QPt6PBnObqkE4lBZlkej7_81Hv1F8ZrgBcFt9yGBWyQQC4pzB1OOnxTnpKt4WVX1t6cPNSNnxYsY7zBucMP58-KMYk5oXbHz4tf24CDsTExGoaXbGb8Dl8tLrUEl5DVa-QGs-QHBuB1aGxm8tCImdBX8z3SL1kIlHxBFwg25J9xkvTokKFfeendA22TGyYp0VJ9YHfx4dDIObZXQ2tshHvUfvQP0WYRsjW6yV9xb4VIWe4cyvAomjyks2phRouuobmE04mXxTAsb4dX9e1F8XV_erD6Vmy9X16vlplSMs1RWXIPktWgbTqTo6qrBHSEK14wOkrV80J2ipKW0hlbWTGChWgKd1JUEzASrLor3J9998N8niKkfTVRg84jgp9i3eaFt29BHkJR2GNcVz-Tbf8g7PwWXvzFDDWe4aTL07gTthIXeOO1TEGq27JeUtSx_gc9Wi_9Q-Qx5SSovVpvc_0tATgIVfIwBdL8PZhTh0BPcz_nqc77yFf2cr37OV9a8uZ93kiMMD4o_gcoAPwFzWzhnDUgI6RHWvwFj4uEI</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Layman, Hans</creator><creator>Rahnemai-Azar, Amir A</creator><creator>Pham, Si M.</creator><creator>Tsechpenakis, Gavriil</creator><creator>Andreopoulos, Fotios M.</creator><general>Mary Ann Liebert, 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>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</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>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>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110101</creationdate><title>Synergistic Angiogenic Effect of Codelivering Fibroblast Growth Factor 2 and Granulocyte-Colony Stimulating Factor from Fibrin Scaffolds and Bone Marrow Transplantation in Critical Limb Ischemia</title><author>Layman, Hans ; 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Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Layman, Hans</au><au>Rahnemai-Azar, Amir A</au><au>Pham, Si M.</au><au>Tsechpenakis, Gavriil</au><au>Andreopoulos, Fotios M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic Angiogenic Effect of Codelivering Fibroblast Growth Factor 2 and Granulocyte-Colony Stimulating Factor from Fibrin Scaffolds and Bone Marrow Transplantation in Critical Limb Ischemia</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>17</volume><issue>1-2</issue><spage>243</spage><epage>254</epage><pages>243-254</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Increasing evidence suggests that therapeutic angiogenesis strategies utilizing cytokines and stem cells are necessary to treat traumatic vascular events such as critical limb ischemia and peripheral artery disease. In this study, basic fibroblast growth factor 2 (FGF-2) and granulocyte-colony stimulating factor (G-CSF) were immobilized in fibrin matrices and codelivered in combination with unfractionated bone marrow cells. Hindlimb ischemia was induced on young (6–7 weeks) Balb/C mice, and fibrin gels containing 100 ng/mL of FGF-2 and G-CSF were implanted adjacent to the ligation points. In addition, 1 × 10
6
bone marrow (BM) cells were injected into five locations in the ischemic muscle immediately after ligation and artery excision. Hindlimb reperfusion was determined by Laser Doppler Perfusion Imaging and immunohistochemistry for CD31+ and smooth muscle actin-positive cells at 2, 4, and 8 weeks postsurgery to identify capillary formation and maturation. A fluorescent vessel painting technique was also utilized to determine the extent of angiogenesis and arteriogenesis in the hindlimb at 8 weeks postsurgery. The codelivery of FGF-2 and G-CSF in combination with BM cells led to enhanced therapeutic recovery in critical limb ischemia Balb/C mice after 8 weeks of treatment with 87.2% blood flow recovery and a significant increase (
p
< 0.05) in capillary formation in comparison to growth factor delivery or BM cell administration alone.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>20712534</pmid><doi>10.1089/ten.tea.2010.0270</doi><tpages>12</tpages></addata></record> |
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| ispartof | Tissue engineering. Part A, 2011-01, Vol.17 (1-2), p.243-254 |
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| subjects | Animals Bone marrow Bone Marrow Cells - cytology Bone Marrow Cells - drug effects Bone Marrow Transplantation - methods Care and treatment Cattle Cells, Cultured Cytokines Fibroblast Growth Factor 2 - chemistry Fibroblast Growth Factor 2 - pharmacology Fibroblast growth factors Granulocyte colony-stimulating factor Granulocyte Colony-Stimulating Factor - chemistry Granulocyte Colony-Stimulating Factor - pharmacology Health aspects Hindlimb - pathology Humans Immunohistochemistry Ischemia Ischemia - therapy Male Mice Mice, Inbred BALB C Original Articles Physiological aspects Risk factors Rodents Stem cells Tissue engineering Tissue Scaffolds Transplantation |
| title | Synergistic Angiogenic Effect of Codelivering Fibroblast Growth Factor 2 and Granulocyte-Colony Stimulating Factor from Fibrin Scaffolds and Bone Marrow Transplantation in Critical Limb Ischemia |
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