Hypoxia-Preconditioned Bone Marrow Mesenchymal Stem Cells Improved Cerebral Collateral Circulation and Stroke Outcome in Mice
Adequate collateral circulation can remarkably improve patient prognoses for patients experiencing ischemic stroke. Hypoxic preconditioning enhances the regenerative properties of bone marrow mesenchymal stem cells (BMSCs). Rabep2 (RAB GTPase binding effector protein 2) is a key protein in collatera...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2023-07, Vol.43 (7), p.1281-1294 |
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| creator | Tian, Hao Yang, Xinxuan Zhao, Jiahui Liu, Xiran Liu, Xin Cai, Yuan Wehbe, Alexandra Ding, Yuchuan Yu, Shanping Wei, Ling Liu, Liping |
| description | Adequate collateral circulation can remarkably improve patient prognoses for patients experiencing ischemic stroke. Hypoxic preconditioning enhances the regenerative properties of bone marrow mesenchymal stem cells (BMSCs). Rabep2 (RAB GTPase binding effector protein 2) is a key protein in collateral remodeling. We investigated whether BMSCs and hypoxia-preconditioned BMSCs (H-BMSCs) augment collateral circulation poststroke, particularly through Rabep2 regulation.
BMSCs or H-BMSCs (1×10
) were delivered intranasally in ischemic mice with distal middle cerebral artery occlusion at 6 hours poststroke. Two-photon microscopic imaging and vessel painting methods were used to analyze collateral remodeling. Blood flow, vascular density, infarct volume, and gait analysis were assessed to evaluate poststroke outcomes. Expressions of proangiogenic marker VEGF (vascular endothelial growth factor) and Rabep2 were determined by Western blotting. Western blot, EdU (5-ethynyl-2'-deoxyuridine) incorporation, and tube formation assays were conducted on cultured endothelial cells treated with BMSCs.
BMSCs were more effectively transplanted in the ischemic brain after hypoxic preconditioning. The ipsilateral collateral diameter was increased by BMSCs and strengthened by H-BMSCs ( |
| doi_str_mv | 10.1161/ATVBAHA.122.318559 |
| format | Article |
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BMSCs or H-BMSCs (1×10
) were delivered intranasally in ischemic mice with distal middle cerebral artery occlusion at 6 hours poststroke. Two-photon microscopic imaging and vessel painting methods were used to analyze collateral remodeling. Blood flow, vascular density, infarct volume, and gait analysis were assessed to evaluate poststroke outcomes. Expressions of proangiogenic marker VEGF (vascular endothelial growth factor) and Rabep2 were determined by Western blotting. Western blot, EdU (5-ethynyl-2'-deoxyuridine) incorporation, and tube formation assays were conducted on cultured endothelial cells treated with BMSCs.
BMSCs were more effectively transplanted in the ischemic brain after hypoxic preconditioning. The ipsilateral collateral diameter was increased by BMSCs and strengthened by H-BMSCs (
<0.05). BMSCs increased peri-infarct blood flow and vascular density and reduced infarct volume, gait deficits (
<0.05), and furthermore by H-BMSCs (
<0.05). VEGF and Rabep2 protein expression was increased by BMSCs (
<0.05), which was enhanced by preconditioning (
<0.01). Additionally, BMSCs increased Rabep2 expression, proliferation, and tube formation of endothelial cells in vitro (
<0.05). H-BMSCs enhanced these effects (
<0.05), which were annulled by Rabep2 knockdown.
BMSCs increased collateral circulation and improved poststroke outcomes, through the upregulation of Rabep2. These effects were enhanced by hypoxic preconditioning.]]></description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.122.318559</identifier><identifier>PMID: 37226732</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins</publisher><subject>Animals ; Bone Marrow Cells ; Collateral Circulation ; Endothelial Cells - metabolism ; Hypoxia ; Infarction ; Ischemia ; Ischemic Preconditioning - methods ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stem Cells - metabolism ; Mice ; Stroke - therapy ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2023-07, Vol.43 (7), p.1281-1294</ispartof><rights>Lippincott Williams & Wilkins</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3489-4fa3f11902150ad05340e94a093a313421bcc6d2d2124bdf43b4740e4783608b3</citedby><cites>FETCH-LOGICAL-c3489-4fa3f11902150ad05340e94a093a313421bcc6d2d2124bdf43b4740e4783608b3</cites><orcidid>0000-0003-2943-055X ; 0000-0001-7128-7545 ; 0000-0003-2731-3659</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37226732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Hao</creatorcontrib><creatorcontrib>Yang, Xinxuan</creatorcontrib><creatorcontrib>Zhao, Jiahui</creatorcontrib><creatorcontrib>Liu, Xiran</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Cai, Yuan</creatorcontrib><creatorcontrib>Wehbe, Alexandra</creatorcontrib><creatorcontrib>Ding, Yuchuan</creatorcontrib><creatorcontrib>Yu, Shanping</creatorcontrib><creatorcontrib>Wei, Ling</creatorcontrib><creatorcontrib>Liu, Liping</creatorcontrib><title>Hypoxia-Preconditioned Bone Marrow Mesenchymal Stem Cells Improved Cerebral Collateral Circulation and Stroke Outcome in Mice</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description><![CDATA[Adequate collateral circulation can remarkably improve patient prognoses for patients experiencing ischemic stroke. Hypoxic preconditioning enhances the regenerative properties of bone marrow mesenchymal stem cells (BMSCs). Rabep2 (RAB GTPase binding effector protein 2) is a key protein in collateral remodeling. We investigated whether BMSCs and hypoxia-preconditioned BMSCs (H-BMSCs) augment collateral circulation poststroke, particularly through Rabep2 regulation.
BMSCs or H-BMSCs (1×10
) were delivered intranasally in ischemic mice with distal middle cerebral artery occlusion at 6 hours poststroke. Two-photon microscopic imaging and vessel painting methods were used to analyze collateral remodeling. Blood flow, vascular density, infarct volume, and gait analysis were assessed to evaluate poststroke outcomes. Expressions of proangiogenic marker VEGF (vascular endothelial growth factor) and Rabep2 were determined by Western blotting. Western blot, EdU (5-ethynyl-2'-deoxyuridine) incorporation, and tube formation assays were conducted on cultured endothelial cells treated with BMSCs.
BMSCs were more effectively transplanted in the ischemic brain after hypoxic preconditioning. The ipsilateral collateral diameter was increased by BMSCs and strengthened by H-BMSCs (
<0.05). BMSCs increased peri-infarct blood flow and vascular density and reduced infarct volume, gait deficits (
<0.05), and furthermore by H-BMSCs (
<0.05). VEGF and Rabep2 protein expression was increased by BMSCs (
<0.05), which was enhanced by preconditioning (
<0.01). Additionally, BMSCs increased Rabep2 expression, proliferation, and tube formation of endothelial cells in vitro (
<0.05). H-BMSCs enhanced these effects (
<0.05), which were annulled by Rabep2 knockdown.
BMSCs increased collateral circulation and improved poststroke outcomes, through the upregulation of Rabep2. These effects were enhanced by hypoxic preconditioning.]]></description><subject>Animals</subject><subject>Bone Marrow Cells</subject><subject>Collateral Circulation</subject><subject>Endothelial Cells - metabolism</subject><subject>Hypoxia</subject><subject>Infarction</subject><subject>Ischemia</subject><subject>Ischemic Preconditioning - methods</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mice</subject><subject>Stroke - therapy</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kU9v1DAQxS0EoqXwBTggH7lkscfOv-M2KmylropE4Wo5zkQb6sSLnbDsge_OlF042J6Rf-9p_MzYWylWUhbyw_rh2_V6s15JgJWSVZ7Xz9ilzEFnulDFc6pFWWd5oeGCvUrpuxBCA4iX7EKVAEWp4JL93hz34ddgs88RXZi6YR7ChB2_pp1vbYzhwLeYcHK742g9_zLjyBv0PvHbcR_DT2IbjNhGumyC93bGv-UQ3UINuXE7daSL4RH5_TK7MCIfJr4dHL5mL3rrE745n1fs68ebh2aT3d1_um3Wd5lTuqoz3VvVS1kLkLmwnciVFlhrK2pllVQaZOtc0UEHEnTb9Vq1uiREl5UqRNWqK_b-5EsT_1gwzWYckqNX2AnDkgxUsoayACkIhRPqYkgpYm_2cRhtPBopzFPs5hy7odjNKXYSvTv7L-2I3X_Jv5wJ0CfgEDwFlB79csBodmj9vDNPH0OD5hkIUKKkNqMla_UH5OeNwA</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Tian, Hao</creator><creator>Yang, Xinxuan</creator><creator>Zhao, Jiahui</creator><creator>Liu, Xiran</creator><creator>Liu, Xin</creator><creator>Cai, Yuan</creator><creator>Wehbe, Alexandra</creator><creator>Ding, Yuchuan</creator><creator>Yu, Shanping</creator><creator>Wei, Ling</creator><creator>Liu, Liping</creator><general>Lippincott Williams & Wilkins</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>7X8</scope><orcidid>https://orcid.org/0000-0003-2943-055X</orcidid><orcidid>https://orcid.org/0000-0001-7128-7545</orcidid><orcidid>https://orcid.org/0000-0003-2731-3659</orcidid></search><sort><creationdate>20230701</creationdate><title>Hypoxia-Preconditioned Bone Marrow Mesenchymal Stem Cells Improved Cerebral Collateral Circulation and Stroke Outcome in Mice</title><author>Tian, Hao ; Yang, Xinxuan ; Zhao, Jiahui ; Liu, Xiran ; Liu, Xin ; Cai, Yuan ; Wehbe, Alexandra ; Ding, Yuchuan ; Yu, Shanping ; Wei, Ling ; Liu, Liping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3489-4fa3f11902150ad05340e94a093a313421bcc6d2d2124bdf43b4740e4783608b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Bone Marrow Cells</topic><topic>Collateral Circulation</topic><topic>Endothelial Cells - metabolism</topic><topic>Hypoxia</topic><topic>Infarction</topic><topic>Ischemia</topic><topic>Ischemic Preconditioning - methods</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mice</topic><topic>Stroke - therapy</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Hao</creatorcontrib><creatorcontrib>Yang, Xinxuan</creatorcontrib><creatorcontrib>Zhao, Jiahui</creatorcontrib><creatorcontrib>Liu, Xiran</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Cai, Yuan</creatorcontrib><creatorcontrib>Wehbe, Alexandra</creatorcontrib><creatorcontrib>Ding, Yuchuan</creatorcontrib><creatorcontrib>Yu, Shanping</creatorcontrib><creatorcontrib>Wei, Ling</creatorcontrib><creatorcontrib>Liu, Liping</creatorcontrib><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><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tian, Hao</au><au>Yang, Xinxuan</au><au>Zhao, Jiahui</au><au>Liu, Xiran</au><au>Liu, Xin</au><au>Cai, Yuan</au><au>Wehbe, Alexandra</au><au>Ding, Yuchuan</au><au>Yu, Shanping</au><au>Wei, Ling</au><au>Liu, Liping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypoxia-Preconditioned Bone Marrow Mesenchymal Stem Cells Improved Cerebral Collateral Circulation and Stroke Outcome in Mice</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>43</volume><issue>7</issue><spage>1281</spage><epage>1294</epage><pages>1281-1294</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract><![CDATA[Adequate collateral circulation can remarkably improve patient prognoses for patients experiencing ischemic stroke. Hypoxic preconditioning enhances the regenerative properties of bone marrow mesenchymal stem cells (BMSCs). Rabep2 (RAB GTPase binding effector protein 2) is a key protein in collateral remodeling. We investigated whether BMSCs and hypoxia-preconditioned BMSCs (H-BMSCs) augment collateral circulation poststroke, particularly through Rabep2 regulation.
BMSCs or H-BMSCs (1×10
) were delivered intranasally in ischemic mice with distal middle cerebral artery occlusion at 6 hours poststroke. Two-photon microscopic imaging and vessel painting methods were used to analyze collateral remodeling. Blood flow, vascular density, infarct volume, and gait analysis were assessed to evaluate poststroke outcomes. Expressions of proangiogenic marker VEGF (vascular endothelial growth factor) and Rabep2 were determined by Western blotting. Western blot, EdU (5-ethynyl-2'-deoxyuridine) incorporation, and tube formation assays were conducted on cultured endothelial cells treated with BMSCs.
BMSCs were more effectively transplanted in the ischemic brain after hypoxic preconditioning. The ipsilateral collateral diameter was increased by BMSCs and strengthened by H-BMSCs (
<0.05). BMSCs increased peri-infarct blood flow and vascular density and reduced infarct volume, gait deficits (
<0.05), and furthermore by H-BMSCs (
<0.05). VEGF and Rabep2 protein expression was increased by BMSCs (
<0.05), which was enhanced by preconditioning (
<0.01). Additionally, BMSCs increased Rabep2 expression, proliferation, and tube formation of endothelial cells in vitro (
<0.05). H-BMSCs enhanced these effects (
<0.05), which were annulled by Rabep2 knockdown.
BMSCs increased collateral circulation and improved poststroke outcomes, through the upregulation of Rabep2. These effects were enhanced by hypoxic preconditioning.]]></abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins</pub><pmid>37226732</pmid><doi>10.1161/ATVBAHA.122.318559</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-2943-055X</orcidid><orcidid>https://orcid.org/0000-0001-7128-7545</orcidid><orcidid>https://orcid.org/0000-0003-2731-3659</orcidid></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2023-07, Vol.43 (7), p.1281-1294 |
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| subjects | Animals Bone Marrow Cells Collateral Circulation Endothelial Cells - metabolism Hypoxia Infarction Ischemia Ischemic Preconditioning - methods Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stem Cells - metabolism Mice Stroke - therapy Vascular Endothelial Growth Factor A - metabolism |
| title | Hypoxia-Preconditioned Bone Marrow Mesenchymal Stem Cells Improved Cerebral Collateral Circulation and Stroke Outcome in Mice |
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