X-Ray-Visible Microcapsules Containing Mesenchymal Stem Cells Improve Hind Limb Perfusion in a Rabbit Model of Peripheral Arterial Disease
The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cel...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2012-06, Vol.30 (6), p.1286-1296 |
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| creator | Kedziorek, Dorota A. Hofmann, Lawrence V. Fu, Yingli Gilson, Wesley D. Cosby, Kenyatta M. Kohl, Bernard Barnett, Brad P. Simons, Brian W. Walczak, Piotr Bulte, Jeff W.M. Gabrielson, Kathleen Kraitchman, Dara L. |
| description | The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC‐Xcaps.) In vitro MSC‐Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x‐ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC‐Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast‐to‐noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC‐Xcap‐treated animals versus empty Xcaps. Post‐mortem immunohistopathology of vessel density by anti‐CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap‐MSC‐treated animals versus empty Xcaps. MSC‐Xcaps represent the first x‐ray‐visible cellular therapeutic with enhanced efficacy for PAD treatment. STEM CELLS2012;30:1286–1296 |
| doi_str_mv | 10.1002/stem.1096 |
| format | Article |
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Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC‐Xcaps.) In vitro MSC‐Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x‐ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC‐Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast‐to‐noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC‐Xcap‐treated animals versus empty Xcaps. Post‐mortem immunohistopathology of vessel density by anti‐CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap‐MSC‐treated animals versus empty Xcaps. MSC‐Xcaps represent the first x‐ray‐visible cellular therapeutic with enhanced efficacy for PAD treatment. STEM CELLS2012;30:1286–1296</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.1096</identifier><identifier>PMID: 22438076</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Angiogenesis inducing agents ; Animals ; Barium sulfate ; Cone-beam computed tomography ; Cone-Beam Computed Tomography - methods ; Disease Models, Animal ; Hindlimb - blood supply ; Hindlimb - pathology ; Immunohistochemistry ; Male ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - physiology ; Peripheral arterial disease ; Peripheral Arterial Disease - physiopathology ; Peripheral Arterial Disease - surgery ; Rabbits ; X-Rays</subject><ispartof>Stem cells (Dayton, Ohio), 2012-06, Vol.30 (6), p.1286-1296</ispartof><rights>Copyright © 2012 AlphaMed Press</rights><rights>Copyright © 2012 AlphaMed Press.</rights><rights>AlphaMed Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4816-3f7c87591c18203f9298b6b81a9ba680fd2ea124fb3ec5480267d171142652123</citedby><cites>FETCH-LOGICAL-c4816-3f7c87591c18203f9298b6b81a9ba680fd2ea124fb3ec5480267d171142652123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22438076$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kedziorek, Dorota A.</creatorcontrib><creatorcontrib>Hofmann, Lawrence V.</creatorcontrib><creatorcontrib>Fu, Yingli</creatorcontrib><creatorcontrib>Gilson, Wesley D.</creatorcontrib><creatorcontrib>Cosby, Kenyatta M.</creatorcontrib><creatorcontrib>Kohl, Bernard</creatorcontrib><creatorcontrib>Barnett, Brad P.</creatorcontrib><creatorcontrib>Simons, Brian W.</creatorcontrib><creatorcontrib>Walczak, Piotr</creatorcontrib><creatorcontrib>Bulte, Jeff W.M.</creatorcontrib><creatorcontrib>Gabrielson, Kathleen</creatorcontrib><creatorcontrib>Kraitchman, Dara L.</creatorcontrib><title>X-Ray-Visible Microcapsules Containing Mesenchymal Stem Cells Improve Hind Limb Perfusion in a Rabbit Model of Peripheral Arterial Disease</title><title>Stem cells (Dayton, Ohio)</title><addtitle>STEM CELLS</addtitle><description>The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC‐Xcaps.) In vitro MSC‐Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x‐ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC‐Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast‐to‐noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC‐Xcap‐treated animals versus empty Xcaps. Post‐mortem immunohistopathology of vessel density by anti‐CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap‐MSC‐treated animals versus empty Xcaps. MSC‐Xcaps represent the first x‐ray‐visible cellular therapeutic with enhanced efficacy for PAD treatment. STEM CELLS2012;30:1286–1296</description><subject>Angiogenesis inducing agents</subject><subject>Animals</subject><subject>Barium sulfate</subject><subject>Cone-beam computed tomography</subject><subject>Cone-Beam Computed Tomography - methods</subject><subject>Disease Models, Animal</subject><subject>Hindlimb - blood supply</subject><subject>Hindlimb - pathology</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>Peripheral arterial disease</subject><subject>Peripheral Arterial Disease - physiopathology</subject><subject>Peripheral Arterial Disease - surgery</subject><subject>Rabbits</subject><subject>X-Rays</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UcFu1DAUjBCIloUDP4AscYFDqJ8TO84FqVrabsUuoLYUbpaTfem6TexgJ4X9Bb4ar3ZZARInP2vmjcczSfIc6BuglB2FAbs4leJBcgg8L9O8BPkwzlSIlNOyPEiehHBLKeRcysfJAWN5JmkhDpOfX9MLvU6vTTBVi2Rhau9q3YexxUCmzg7aWGNvyAID2nq17nRLLuNzZIptG8h513t3j2Rm7JLMTVeRT-ibMRhnibFEkwtdVWYgC7fElrhmA5t-hT7KHPshXuLwzgTUAZ8mjxrdBny2OyfJ59OTq-ksnX88O58ez9M6lyDSrClqWfASapCMZk3JSlmJSoIuKy0kbZYMNbC8qTKseS4pE8USCoCcCc6AZZPk7Va3H6sOlzXaIdpRvTed9mvltFF_I9as1I27V5ngWc4gCrzaCXj3bcQwqM6EOuahLboxKKAQQ5d5DHmSvPyHeutGb-P3FADw6EjChvV6y4rhh-Cx2ZsBqjYNq03DatNw5L740_2e-bvSSDjaEr6bFtf_V1KXVyeLnWS63TAR_LHf0P5OiSIruPry4UzNTvmcv78GBdkvTnPAAg</recordid><startdate>201206</startdate><enddate>201206</enddate><creator>Kedziorek, Dorota A.</creator><creator>Hofmann, Lawrence V.</creator><creator>Fu, Yingli</creator><creator>Gilson, Wesley D.</creator><creator>Cosby, Kenyatta M.</creator><creator>Kohl, Bernard</creator><creator>Barnett, Brad P.</creator><creator>Simons, Brian W.</creator><creator>Walczak, Piotr</creator><creator>Bulte, Jeff W.M.</creator><creator>Gabrielson, Kathleen</creator><creator>Kraitchman, Dara L.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Oxford University Press</general><scope>BSCLL</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201206</creationdate><title>X-Ray-Visible Microcapsules Containing Mesenchymal Stem Cells Improve Hind Limb Perfusion in a Rabbit Model of Peripheral Arterial Disease</title><author>Kedziorek, Dorota A. ; Hofmann, Lawrence V. ; Fu, Yingli ; Gilson, Wesley D. ; Cosby, Kenyatta M. ; Kohl, Bernard ; Barnett, Brad P. ; Simons, Brian W. ; Walczak, Piotr ; Bulte, Jeff W.M. ; Gabrielson, Kathleen ; Kraitchman, Dara L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4816-3f7c87591c18203f9298b6b81a9ba680fd2ea124fb3ec5480267d171142652123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Angiogenesis inducing agents</topic><topic>Animals</topic><topic>Barium sulfate</topic><topic>Cone-beam computed tomography</topic><topic>Cone-Beam Computed Tomography - methods</topic><topic>Disease Models, Animal</topic><topic>Hindlimb - blood supply</topic><topic>Hindlimb - pathology</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - physiology</topic><topic>Peripheral arterial disease</topic><topic>Peripheral Arterial Disease - physiopathology</topic><topic>Peripheral Arterial Disease - surgery</topic><topic>Rabbits</topic><topic>X-Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kedziorek, Dorota A.</creatorcontrib><creatorcontrib>Hofmann, Lawrence V.</creatorcontrib><creatorcontrib>Fu, Yingli</creatorcontrib><creatorcontrib>Gilson, Wesley D.</creatorcontrib><creatorcontrib>Cosby, Kenyatta M.</creatorcontrib><creatorcontrib>Kohl, Bernard</creatorcontrib><creatorcontrib>Barnett, Brad P.</creatorcontrib><creatorcontrib>Simons, Brian W.</creatorcontrib><creatorcontrib>Walczak, Piotr</creatorcontrib><creatorcontrib>Bulte, Jeff W.M.</creatorcontrib><creatorcontrib>Gabrielson, Kathleen</creatorcontrib><creatorcontrib>Kraitchman, Dara L.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kedziorek, Dorota A.</au><au>Hofmann, Lawrence V.</au><au>Fu, Yingli</au><au>Gilson, Wesley D.</au><au>Cosby, Kenyatta M.</au><au>Kohl, Bernard</au><au>Barnett, Brad P.</au><au>Simons, Brian W.</au><au>Walczak, Piotr</au><au>Bulte, Jeff W.M.</au><au>Gabrielson, Kathleen</au><au>Kraitchman, Dara L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>X-Ray-Visible Microcapsules Containing Mesenchymal Stem Cells Improve Hind Limb Perfusion in a Rabbit Model of Peripheral Arterial Disease</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>STEM CELLS</addtitle><date>2012-06</date><risdate>2012</risdate><volume>30</volume><issue>6</issue><spage>1286</spage><epage>1296</epage><pages>1286-1296</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC‐Xcaps.) In vitro MSC‐Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x‐ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC‐Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast‐to‐noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC‐Xcap‐treated animals versus empty Xcaps. Post‐mortem immunohistopathology of vessel density by anti‐CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap‐MSC‐treated animals versus empty Xcaps. MSC‐Xcaps represent the first x‐ray‐visible cellular therapeutic with enhanced efficacy for PAD treatment. STEM CELLS2012;30:1286–1296</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22438076</pmid><doi>10.1002/stem.1096</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Stem cells (Dayton, Ohio), 2012-06, Vol.30 (6), p.1286-1296 |
| issn | 1066-5099 1549-4918 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Angiogenesis inducing agents Animals Barium sulfate Cone-beam computed tomography Cone-Beam Computed Tomography - methods Disease Models, Animal Hindlimb - blood supply Hindlimb - pathology Immunohistochemistry Male Mesenchymal Stem Cell Transplantation - methods Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - physiology Peripheral arterial disease Peripheral Arterial Disease - physiopathology Peripheral Arterial Disease - surgery Rabbits X-Rays |
| title | X-Ray-Visible Microcapsules Containing Mesenchymal Stem Cells Improve Hind Limb Perfusion in a Rabbit Model of Peripheral Arterial Disease |
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