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Xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis
Background The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem...
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| Published in: | Xenotransplantation (Københaven) 2021-07, Vol.28 (4), p.e12693-n/a |
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| container_title | Xenotransplantation (Københaven) |
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| creator | Yamada, Hideaki Sakata, Naoaki Nishimura, Masuhiro Tanaka, Tomoko Shimizu, Masayuki Yoshimatsu, Gumpei Kawakami, Ryo Wada, Hideichi Sawamoto, Osamu Matsumoto, Shinichi Kodama, Shohta |
| description | Background
The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells (npBM‐MSCs).
Methods
Neonatal porcine bone marrow‐derived mesenchymal stem cells were transplanted to ischemic hind limbs of male C57BL/6J mice (npBM‐MSCs group). Mice with syngeneic transplantation of mouse BM‐MSCs (mBM‐MSCs group) were also prepared for comparison. The angiogenic effects were evaluated by recovery of blood flow on laser Doppler imaging, histologic findings, and genetic and protein levels of angiogenic factors.
Results
Regarding laser Doppler assessments, blood flow in the hind limb was rapidly recovered in the npBM‐MSCs group, compared with that in the mBM‐MSCs group (P = .016). Compared with the mBM‐MSCs group, the npBM‐MSCs group had early and prominent lymphangiogenesis [P |
| doi_str_mv | 10.1111/xen.12693 |
| format | article |
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The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells (npBM‐MSCs).
Methods
Neonatal porcine bone marrow‐derived mesenchymal stem cells were transplanted to ischemic hind limbs of male C57BL/6J mice (npBM‐MSCs group). Mice with syngeneic transplantation of mouse BM‐MSCs (mBM‐MSCs group) were also prepared for comparison. The angiogenic effects were evaluated by recovery of blood flow on laser Doppler imaging, histologic findings, and genetic and protein levels of angiogenic factors.
Results
Regarding laser Doppler assessments, blood flow in the hind limb was rapidly recovered in the npBM‐MSCs group, compared with that in the mBM‐MSCs group (P = .016). Compared with the mBM‐MSCs group, the npBM‐MSCs group had early and prominent lymphangiogenesis [P < .05 on both post‐operative days (PODs) 3 and 7] but had similar angiogenesis. Regarding genomic assessments, xenotransplantation of npBM‐MSCs enhanced the expressions of both porcine and murine Vegfc in the hind limbs by POD 3. Interestingly, the level of murine Vegfc expression was significantly higher in the npBM‐MSCs group than in the mBM‐MSCs group on PODs 3 and 7 (P < .001 for both). Furthermore, the secreted VEGFC protein level was higher from npBM‐MSCs than from mBM‐MSCs (P < .001).
Conclusion
Xenotransplantation of npBM‐MSCs contributed to the improvement of hind limb ischemia by both angiogenesis and lymphangiogenesis, especially promotion of the latter. npBM‐MSCs may provide an alternative to autologous and allogeneic MSCs for stem cell therapy of critical limb ischemia.</description><identifier>ISSN: 0908-665X</identifier><identifier>EISSN: 1399-3089</identifier><identifier>DOI: 10.1111/xen.12693</identifier><identifier>PMID: 33960029</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis ; Autografts ; Blood flow ; Bone marrow ; Bone marrow transplantation ; Cell therapy ; Doppler effect ; Ischemia ; Limbs ; lymphangiogenesis ; mesenchymal stem cell ; Mesenchymal stem cells ; neonatal pig ; Neonates ; Stem cell transplantation ; Stem cells ; Syngeneic grafts ; Vascular diseases ; Xenografts ; xenotransplantation</subject><ispartof>Xenotransplantation (Københaven), 2021-07, Vol.28 (4), p.e12693-n/a</ispartof><rights>2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4193-1a22e6fc658242ce3173e2f945b5f136cf27f521fd5789322cc2a7923f62d06e3</citedby><cites>FETCH-LOGICAL-c4193-1a22e6fc658242ce3173e2f945b5f136cf27f521fd5789322cc2a7923f62d06e3</cites><orcidid>0000-0002-3495-4270 ; 0000-0002-8711-4929 ; 0000-0002-0525-1189 ; 0000-0002-9571-342X ; 0000-0003-3737-704X ; 0000-0001-6559-5947 ; 0000-0002-1756-8829 ; 0000-0001-9959-7756 ; 0000-0003-3896-3083</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/33960029$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Hideaki</creatorcontrib><creatorcontrib>Sakata, Naoaki</creatorcontrib><creatorcontrib>Nishimura, Masuhiro</creatorcontrib><creatorcontrib>Tanaka, Tomoko</creatorcontrib><creatorcontrib>Shimizu, Masayuki</creatorcontrib><creatorcontrib>Yoshimatsu, Gumpei</creatorcontrib><creatorcontrib>Kawakami, Ryo</creatorcontrib><creatorcontrib>Wada, Hideichi</creatorcontrib><creatorcontrib>Sawamoto, Osamu</creatorcontrib><creatorcontrib>Matsumoto, Shinichi</creatorcontrib><creatorcontrib>Kodama, Shohta</creatorcontrib><title>Xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis</title><title>Xenotransplantation (Københaven)</title><addtitle>Xenotransplantation</addtitle><description>Background
The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells (npBM‐MSCs).
Methods
Neonatal porcine bone marrow‐derived mesenchymal stem cells were transplanted to ischemic hind limbs of male C57BL/6J mice (npBM‐MSCs group). Mice with syngeneic transplantation of mouse BM‐MSCs (mBM‐MSCs group) were also prepared for comparison. The angiogenic effects were evaluated by recovery of blood flow on laser Doppler imaging, histologic findings, and genetic and protein levels of angiogenic factors.
Results
Regarding laser Doppler assessments, blood flow in the hind limb was rapidly recovered in the npBM‐MSCs group, compared with that in the mBM‐MSCs group (P = .016). Compared with the mBM‐MSCs group, the npBM‐MSCs group had early and prominent lymphangiogenesis [P < .05 on both post‐operative days (PODs) 3 and 7] but had similar angiogenesis. Regarding genomic assessments, xenotransplantation of npBM‐MSCs enhanced the expressions of both porcine and murine Vegfc in the hind limbs by POD 3. Interestingly, the level of murine Vegfc expression was significantly higher in the npBM‐MSCs group than in the mBM‐MSCs group on PODs 3 and 7 (P < .001 for both). Furthermore, the secreted VEGFC protein level was higher from npBM‐MSCs than from mBM‐MSCs (P < .001).
Conclusion
Xenotransplantation of npBM‐MSCs contributed to the improvement of hind limb ischemia by both angiogenesis and lymphangiogenesis, especially promotion of the latter. npBM‐MSCs may provide an alternative to autologous and allogeneic MSCs for stem cell therapy of critical limb ischemia.</description><subject>Angiogenesis</subject><subject>Autografts</subject><subject>Blood flow</subject><subject>Bone marrow</subject><subject>Bone marrow transplantation</subject><subject>Cell therapy</subject><subject>Doppler effect</subject><subject>Ischemia</subject><subject>Limbs</subject><subject>lymphangiogenesis</subject><subject>mesenchymal stem cell</subject><subject>Mesenchymal stem cells</subject><subject>neonatal pig</subject><subject>Neonates</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Syngeneic grafts</subject><subject>Vascular diseases</subject><subject>Xenografts</subject><subject>xenotransplantation</subject><issn>0908-665X</issn><issn>1399-3089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10c1qFTEUB_Agir1WF76ABNzYxbT5mGQmSym1CqVuFO5uyM2c3EmZJGMy03p3PkKfoY_mk5h6WxHBLBIIv_w5OQeh15Qc07JOvkM4pkwq_gStKFeq4qRVT9GKKNJWUor1AXqR8xUhhItWPEcHnCtJCFMrdLeGEOekQ55GHWY9uxhwtDhADHrWI55iMi4A3sSyeZ1SvPn547aH5K6hxx4yBDPsfJF5Bo8NjGPGzk8pXkPGfkn3jwcXejw6v8EumwG803geUly2Ax53fhp02Lq4hQDZZayL_fviJXpm9Zjh1cN5iL5-OPty-rG6-Hz-6fT9RWVqqnhFNWMgrZGiZTUzwGnDgVlVi42wlEtjWWMFo7YXTas4Y8Yw3SjGrWQ9kcAP0bt9bqn92wJ57nyptvxHl2YsuWOC1VxSXjeFvv2HXsUlhVJdUZIVQxtV1NFemRRzTmC7KbnSwl1HSXc_uK4Mrvs9uGLfPCQuGw_9H_k4qQJO9uDGjbD7f1K3PrvcR_4CqOGnTA</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Yamada, Hideaki</creator><creator>Sakata, Naoaki</creator><creator>Nishimura, Masuhiro</creator><creator>Tanaka, Tomoko</creator><creator>Shimizu, Masayuki</creator><creator>Yoshimatsu, Gumpei</creator><creator>Kawakami, Ryo</creator><creator>Wada, Hideichi</creator><creator>Sawamoto, Osamu</creator><creator>Matsumoto, Shinichi</creator><creator>Kodama, Shohta</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3495-4270</orcidid><orcidid>https://orcid.org/0000-0002-8711-4929</orcidid><orcidid>https://orcid.org/0000-0002-0525-1189</orcidid><orcidid>https://orcid.org/0000-0002-9571-342X</orcidid><orcidid>https://orcid.org/0000-0003-3737-704X</orcidid><orcidid>https://orcid.org/0000-0001-6559-5947</orcidid><orcidid>https://orcid.org/0000-0002-1756-8829</orcidid><orcidid>https://orcid.org/0000-0001-9959-7756</orcidid><orcidid>https://orcid.org/0000-0003-3896-3083</orcidid></search><sort><creationdate>202107</creationdate><title>Xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis</title><author>Yamada, Hideaki ; Sakata, Naoaki ; Nishimura, Masuhiro ; Tanaka, Tomoko ; Shimizu, Masayuki ; Yoshimatsu, Gumpei ; Kawakami, Ryo ; Wada, Hideichi ; Sawamoto, Osamu ; Matsumoto, Shinichi ; Kodama, Shohta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4193-1a22e6fc658242ce3173e2f945b5f136cf27f521fd5789322cc2a7923f62d06e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Autografts</topic><topic>Blood flow</topic><topic>Bone marrow</topic><topic>Bone marrow transplantation</topic><topic>Cell therapy</topic><topic>Doppler effect</topic><topic>Ischemia</topic><topic>Limbs</topic><topic>lymphangiogenesis</topic><topic>mesenchymal stem cell</topic><topic>Mesenchymal stem cells</topic><topic>neonatal pig</topic><topic>Neonates</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Syngeneic grafts</topic><topic>Vascular diseases</topic><topic>Xenografts</topic><topic>xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Hideaki</creatorcontrib><creatorcontrib>Sakata, Naoaki</creatorcontrib><creatorcontrib>Nishimura, Masuhiro</creatorcontrib><creatorcontrib>Tanaka, Tomoko</creatorcontrib><creatorcontrib>Shimizu, Masayuki</creatorcontrib><creatorcontrib>Yoshimatsu, Gumpei</creatorcontrib><creatorcontrib>Kawakami, Ryo</creatorcontrib><creatorcontrib>Wada, Hideichi</creatorcontrib><creatorcontrib>Sawamoto, Osamu</creatorcontrib><creatorcontrib>Matsumoto, Shinichi</creatorcontrib><creatorcontrib>Kodama, Shohta</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Xenotransplantation (Københaven)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Hideaki</au><au>Sakata, Naoaki</au><au>Nishimura, Masuhiro</au><au>Tanaka, Tomoko</au><au>Shimizu, Masayuki</au><au>Yoshimatsu, Gumpei</au><au>Kawakami, Ryo</au><au>Wada, Hideichi</au><au>Sawamoto, Osamu</au><au>Matsumoto, Shinichi</au><au>Kodama, Shohta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis</atitle><jtitle>Xenotransplantation (Københaven)</jtitle><addtitle>Xenotransplantation</addtitle><date>2021-07</date><risdate>2021</risdate><volume>28</volume><issue>4</issue><spage>e12693</spage><epage>n/a</epage><pages>e12693-n/a</pages><issn>0908-665X</issn><eissn>1399-3089</eissn><abstract>Background
The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells (npBM‐MSCs).
Methods
Neonatal porcine bone marrow‐derived mesenchymal stem cells were transplanted to ischemic hind limbs of male C57BL/6J mice (npBM‐MSCs group). Mice with syngeneic transplantation of mouse BM‐MSCs (mBM‐MSCs group) were also prepared for comparison. The angiogenic effects were evaluated by recovery of blood flow on laser Doppler imaging, histologic findings, and genetic and protein levels of angiogenic factors.
Results
Regarding laser Doppler assessments, blood flow in the hind limb was rapidly recovered in the npBM‐MSCs group, compared with that in the mBM‐MSCs group (P = .016). Compared with the mBM‐MSCs group, the npBM‐MSCs group had early and prominent lymphangiogenesis [P < .05 on both post‐operative days (PODs) 3 and 7] but had similar angiogenesis. Regarding genomic assessments, xenotransplantation of npBM‐MSCs enhanced the expressions of both porcine and murine Vegfc in the hind limbs by POD 3. Interestingly, the level of murine Vegfc expression was significantly higher in the npBM‐MSCs group than in the mBM‐MSCs group on PODs 3 and 7 (P < .001 for both). Furthermore, the secreted VEGFC protein level was higher from npBM‐MSCs than from mBM‐MSCs (P < .001).
Conclusion
Xenotransplantation of npBM‐MSCs contributed to the improvement of hind limb ischemia by both angiogenesis and lymphangiogenesis, especially promotion of the latter. npBM‐MSCs may provide an alternative to autologous and allogeneic MSCs for stem cell therapy of critical limb ischemia.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33960029</pmid><doi>10.1111/xen.12693</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-3495-4270</orcidid><orcidid>https://orcid.org/0000-0002-8711-4929</orcidid><orcidid>https://orcid.org/0000-0002-0525-1189</orcidid><orcidid>https://orcid.org/0000-0002-9571-342X</orcidid><orcidid>https://orcid.org/0000-0003-3737-704X</orcidid><orcidid>https://orcid.org/0000-0001-6559-5947</orcidid><orcidid>https://orcid.org/0000-0002-1756-8829</orcidid><orcidid>https://orcid.org/0000-0001-9959-7756</orcidid><orcidid>https://orcid.org/0000-0003-3896-3083</orcidid></addata></record> |
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| source | Wiley:Jisc Collections:Wiley Read and Publish Open Access 2024-2025 (reading list) |
| subjects | Angiogenesis Autografts Blood flow Bone marrow Bone marrow transplantation Cell therapy Doppler effect Ischemia Limbs lymphangiogenesis mesenchymal stem cell Mesenchymal stem cells neonatal pig Neonates Stem cell transplantation Stem cells Syngeneic grafts Vascular diseases Xenografts xenotransplantation |
| title | Xenotransplantation of neonatal porcine bone marrow‐derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis |
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