{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:09:27Z","timestamp":1789510167026,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Angiogenesis is a critical part of the endogenous repair process in brain injury and disease, and requires at least two sequential steps. First, angiogenic sprouting of endothelial cells occurs, which entails the initial proliferation of endothelial cells and remodeling of the surrounding extracellular matrix. Second, vessel stabilization is necessary to prevent vascular regression, which relies on vascular smooth muscle recruitment to surround the young vessels. Marrow stromal cells (MSCs) have been shown to promote revascularization after hindlimb ischemia, cardiac ischemia, and stroke. SB623 cells are derived from marrow stromal cells by transfection with a <jats:italic>Notch1 intracellular domain<\/jats:italic> (NICD)-expressing plasmid and are known to elicit functional improvement in experimental stroke. These cells are currently used in human clinical testing for treatment of chronic stroke. In the current study, the angiogenic property of SB623 cells was investigated using cell-based assays.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Angiogenic paracrine factors secreted by SB623 cells and the parental MSCs were identified using the Qantibody Human Angiogenesis Array. To measure the angiogenic activity of conditioned medium from SB623 cells and MSCs, endothelial tube formation in the human umbilical vein endothelial cell (HUVEC) assay and endothelial cell sprouting and branching in the rodent aortic ring assay were quantified. To validate the angiogenic contribution of VEGF in conditioned medium, endothelial cells and aortic rings were treated with SU5416, which inhibits VEGFR2 at low dose.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Conditioned medium from SB623 cells promoted survival and proliferation of endothelial cells under serum-deprived conditions and supports HUVEC vascular tube formation. In a rodent aortic ring assay, there was enhanced endothelial sprouting and branching in response to SB623-derived conditioned medium. SU5416 treatment partially reversed the effect of conditioned medium on endothelial cell survival and proliferation while completely abrogate HUVEC tube formation and endothelial cell sprouting and branching in aortic ring assays.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These data indicate that SB623 cell-secreted angiogenic factors promoted several aspects of angiogenesis, which likely contribute to promoting recovery in the injured brain.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1479-5876-11-81","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T03:32:08Z","timestamp":1364355128000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Comparing the angiogenic potency of na\u00efve marrow stromal cells and Notch-transfected marrow stromal cells"],"prefix":"10.1186","volume":"11","author":[{"given":"Mo","family":"Dao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara C","family":"Tate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McGrogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey C","family":"Case","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,3,27]]},"reference":[{"issue":"5","key":"1464_CR1","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1177\/1073858405278865","volume":"11","author":"RL Zhang","year":"2005","unstructured":"Zhang RL, Zhang ZG, Chopp M: Neurogenesis in the adult ischemic brain: generation, migration, survival, and restorative therapy. Neuroscientist. 2005, 11 (5): 408-416. 10.1177\/1073858405278865.","journal-title":"Neuroscientist"},{"issue":"50","key":"1464_CR2","doi-asserted-by":"publisher","first-page":"13007","DOI":"10.1523\/JNEUROSCI.4323-06.2006","volume":"26","author":"JJ Ohab","year":"2006","unstructured":"Ohab JJ, Fleming S, Blesch A, Carmichael ST: A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006, 26 (50): 13007-13016. 10.1523\/JNEUROSCI.4323-06.2006.","journal-title":"J Neurosci"},{"issue":"7","key":"1464_CR3","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.3727\/096368910X544915","volume":"20","author":"T Morimoto","year":"2011","unstructured":"Morimoto T, Yasuhara T, Kameda M, Baba T, Kuramoto S, Kondo A, Takahashi K, Tajiri N, Wang F, Meng J, Ji YW, Kadota T, Maruo T, Kinugasa K, Miyoshi Y, Shingo T, Borlongan CV, Date I: Striatal stimulation nurtures endogenous neurogenesis and angiogenesis in chronic-phase ischemic stroke rats. Cell Transplant. 2011, 20 (7): 1049-1064. 10.3727\/096368910X544915.","journal-title":"Cell Transplant"},{"issue":"3","key":"1464_CR4","first-page":"149","volume":"47","author":"JH Distler","year":"2003","unstructured":"Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O: Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 2003, 47 (3): 149-161.","journal-title":"Q J Nucl Med"},{"key":"1464_CR5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/1479-5876-6-45","volume":"6","author":"MP Murphy","year":"2008","unstructured":"Murphy MP, Wang H, Patel AN, Kambhampati S, Angle N, Chan K, Marleau AM, Pyszniak A, Carrier E, Ichim TE, Riordan NH: Allogeneic endometrial regenerative cells: an \u2018Off the shelf solution\u2019 for critical limb ischemia?. J Transl Med. 2008, 6: 45-10.1186\/1479-5876-6-45.","journal-title":"J Transl Med"},{"issue":"3","key":"1464_CR6","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1007\/s11481-007-9073-3","volume":"2","author":"Y Fan","year":"2007","unstructured":"Fan Y, Yang GY: Therapeutic angiogenesis for brain ischemia: a brief review. J Neuroimmune Pharmacol. 2007, 2 (3): 284-289. 10.1007\/s11481-007-9073-3.","journal-title":"J Neuroimmune Pharmacol"},{"issue":"1","key":"1464_CR7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1089\/107632703762687573","volume":"9","author":"D Kaigler","year":"2003","unstructured":"Kaigler D, Krebsbach PH, Polverini PJ, Mooney DJ: Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells. Tissue Eng. 2003, 9 (1): 95-103. 10.1089\/107632703762687573.","journal-title":"Tissue Eng"},{"issue":"5","key":"1464_CR8","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1161\/01.RES.0000118601.37875.AC","volume":"94","author":"T Kinnaird","year":"2004","unstructured":"Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE: Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004, 94 (5): 678-685. 10.1161\/01.RES.0000118601.37875.AC.","journal-title":"Circ Res"},{"issue":"12","key":"1464_CR9","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1161\/01.CIR.0000124062.31102.57","volume":"109","author":"T Kinnaird","year":"2004","unstructured":"Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE: Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004, 109 (12): 1543-1549. 10.1161\/01.CIR.0000124062.31102.57.","journal-title":"Circulation"},{"issue":"4","key":"1464_CR10","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/labinvest.2010.202","volume":"91","author":"T Sato","year":"2011","unstructured":"Sato T, Iso Y, Uyama T, Kawachi K, Wakabayashi K, Omori Y, Soda T, Shoji M, Koba S, Yokoyama S, Fukuda N, Saito S, Katagiri T, Kobayashi Y, Takeyama Y, Umezawa A, Suzuki H: Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization. Lab Invest. 2011, 91 (4): 553-564. 10.1038\/labinvest.2010.202.","journal-title":"Lab Invest"},{"key":"1464_CR11","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.brainres.2008.07.116","volume":"1236","author":"Y Omori","year":"2008","unstructured":"Omori Y, Honmou O, Harada K, Suzuki J, Houkin K, Kocsis JD: Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats. Brain Res. 2008, 1236: 30-38.","journal-title":"Brain Res"},{"issue":"2","key":"1464_CR12","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/sj.jcbfm.9600527","volume":"28","author":"T Onda","year":"2008","unstructured":"Onda T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD: Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia. J Cereb Blood Flow Metab. 2008, 28 (2): 329-340. 10.1038\/sj.jcbfm.9600527.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1464_CR13","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.brainres.2008.06.123","volume":"1233","author":"N Pavlichenko","year":"2008","unstructured":"Pavlichenko N, Sokolova I, Vijde S, Shvedova E, Alexandrov G, Krouglyakov P, Fedotova O, Gilerovich EG, Polyntsev DG, Otellin VA: Mesenchymal stem cells transplantation could be beneficial for treatment of experimental ischemic stroke in rats. Brain Res. 2008, 1233: 203-213.","journal-title":"Brain Res"},{"key":"1464_CR14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.brainres.2008.02.042","volume":"1208","author":"C Qu","year":"2008","unstructured":"Qu C, Mahmood A, Lu D, Goussev A, Xiong Y, Chopp M: Treatment of traumatic brain injury in mice with marrow stromal cells. Brain Res. 2008, 1208: 234-239.","journal-title":"Brain Res"},{"issue":"12","key":"1464_CR15","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1172\/JCI200420935","volume":"113","author":"M Dezawa","year":"2004","unstructured":"Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C: Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest. 2004, 113 (12): 1701-1710.","journal-title":"J Clin Invest"},{"key":"1464_CR16","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/1742-2094-8-133","volume":"8","author":"MA Dao","year":"2011","unstructured":"Dao MA, Tate CC, Aizman I, McGrogan M, Case CC: Comparing the immunosuppressive potency of na\u00efve marrow stromal cells and Notch-transfected marrow stromal cells. J Neuroinflammation. 2011, 8: 133-10.1186\/1742-2094-8-133.","journal-title":"J Neuroinflammation"},{"issue":"8","key":"1464_CR17","doi-asserted-by":"publisher","first-page":"973","DOI":"10.3727\/096368910X494885","volume":"19","author":"CC Tate","year":"2010","unstructured":"Tate CC, Fonck C, McGrogan M, Case CC: Human mesenchymal stromal cells and their derivative, SB623 cells, rescue neural cells via trophic support following in vitro ischemia. Cell Transplant. 2010, 19 (8): 973-984. 10.3727\/096368910X494885.","journal-title":"Cell Transplant"},{"issue":"10","key":"1464_CR18","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1089\/scd.2009.0011","volume":"18","author":"T Yasuhara","year":"2009","unstructured":"Yasuhara T, Matsukawa N, Hara K, Maki M, Ali MM, Yu SJ, Bae E, Yu G, Xu L, McGrogan M, Bankiewicz K, Case C, Borlongan CV: Notch-induced rat and human bone marrow stromal cell grafts reduce ischemic cell loss and ameliorate behavioral deficits in chronic stroke animals. Stem Cells Dev. 2009, 18 (10): 1501-1514. 10.1089\/scd.2009.0011.","journal-title":"Stem Cells Dev"},{"issue":"1","key":"1464_CR19","first-page":"99","volume":"59","author":"TA Fong","year":"1999","unstructured":"Fong TA, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, Ullrich A, Hirth KP, McMahon G: SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1\/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. 1999, 59 (1): 99-106.","journal-title":"Cancer Res"},{"issue":"6","key":"1464_CR20","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1073\/pnas.94.6.2204","volume":"94","author":"GF Hu","year":"1997","unstructured":"Hu GF, Riordan JF, Vallee BL: A putative angiogenin receptor in angiogenin-responsive human endothelial cells. Proc Natl Acad Sci U S A. 1997, 94 (6): 2204-2209. 10.1073\/pnas.94.6.2204.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"25","key":"1464_CR21","doi-asserted-by":"publisher","first-page":"12096","DOI":"10.1073\/pnas.91.25.12096","volume":"91","author":"G Hu","year":"1994","unstructured":"Hu G, Riordan JF, Vallee BL: Angiogenin promotes invasiveness of cultured endothelial cells by stimulation of cell-associated proteolytic activities. Proc Natl Acad Sci U S A. 1994, 91 (25): 12096-12100. 10.1073\/pnas.91.25.12096.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"1464_CR22","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/sj.onc.1208223","volume":"24","author":"K Kishimoto","year":"2005","unstructured":"Kishimoto K, Liu S, Tsuji T, Olson KA, Hu GF: Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis. Oncogene. 2005, 24 (3): 445-456. 10.1038\/sj.onc.1208223.","journal-title":"Oncogene"},{"issue":"17","key":"1464_CR23","doi-asserted-by":"publisher","first-page":"11205","DOI":"10.1073\/pnas.172161899","volume":"99","author":"IB Lobov","year":"2002","unstructured":"Lobov IB, Brooks PC, Lang RA: Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci U S A. 2002, 99 (17): 11205-11210. 10.1073\/pnas.172161899.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"1464_CR24","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0014-5793(98)00283-X","volume":"425","author":"R Abramovitch","year":"1998","unstructured":"Abramovitch R, Neeman M, Reich R, Stein I, Keshet E, Abraham J, Solomon A, Marikovsky M: Intercellular communication between vascular smooth muscle and endothelial cells mediated by heparin-binding epidermal growth factor-like growth factor and vascular endothelial growth factor. FEBS Lett. 1998, 425 (3): 441-447. 10.1016\/S0014-5793(98)00283-X.","journal-title":"FEBS Lett"},{"issue":"7","key":"1464_CR25","doi-asserted-by":"publisher","first-page":"5096","DOI":"10.1074\/jbc.275.7.5096","volume":"275","author":"LW Wu","year":"2000","unstructured":"Wu LW, Mayo LD, Dunbar JD, Kessler KM, Baerwald MR, Jaffe EA, Wang D, Warren RS, Donner DB: Utilization of distinct signaling pathways by receptors for vascular endothelial cell growth factor and other mitogens in the induction of endothelial cell proliferation. J Biol Chem. 2000, 275 (7): 5096-5103. 10.1074\/jbc.275.7.5096.","journal-title":"J Biol Chem"},{"issue":"12","key":"1464_CR26","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1161\/hq1201.099432","volume":"21","author":"S Yang","year":"2001","unstructured":"Yang S, Xin X, Zlot C, Ingle G, Fuh G, Li B, Moffat B, de Vos AM, Gerritsen ME: Vascular endothelial cell growth factor-driven endothelial tube formation is mediated by vascular endothelial cell growth factor receptor-2, a kinase insert domain-containing receptor. Arterioscler Thromb Vasc Biol. 2001, 21 (12): 1934-1940. 10.1161\/hq1201.099432.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"1464_CR27","first-page":"181","volume":"143","author":"S Villaschi","year":"1993","unstructured":"Villaschi S, Nicosia RF: Angiogenic role of endogenous basic fibroblast growth factor released by rat aorta after injury. Am J Pathol. 1993, 143 (1): 181-190.","journal-title":"Am J Pathol"},{"issue":"13","key":"1464_CR28","doi-asserted-by":"publisher","first-page":"5270","DOI":"10.1158\/0008-5472.CAN-10-0012","volume":"70","author":"SB Coffelt","year":"2010","unstructured":"Coffelt SB, Tal AO, Scholz A, De Palma M, Patel S, Urbich C, Biswas SK, Murdoch C, Plate KH, Reiss Y, Lewis CE: Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions. Cancer Res. 2010, 70 (13): 5270-5280. 10.1158\/0008-5472.CAN-10-0012.","journal-title":"Cancer Res"},{"issue":"5 Pt 2","key":"1464_CR29","first-page":"H1713","volume":"260","author":"U Ikeda","year":"1991","unstructured":"Ikeda U, Ikeda M, Oohara T, Oguchi A, Kamitani T, Tsuruya Y, Kano S: Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner. Am J Physiol. 1991, 260 (5 Pt 2): H1713-H1717.","journal-title":"Am J Physiol"},{"issue":"1","key":"1464_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1161\/01.RES.75.1.1","volume":"75","author":"TL Yue","year":"1994","unstructured":"Yue TL, Wang X, Sung CP, Olson B, McKenna PJ, Gu JL, Feuerstein GZ: Interleukin-8. A mitogen and chemoattractant for vascular smooth muscle cells. Circ Res. 1994, 75 (1): 1-7. 10.1161\/01.RES.75.1.1.","journal-title":"Circ Res"},{"issue":"2","key":"1464_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3109\/08977199109000278","volume":"5","author":"N Ferrara","year":"1991","unstructured":"Ferrara N, Winer J, Burton T: Aortic smooth muscle cells express and secrete vascular endothelial growth factor. Growth Factors. 1991, 5 (2): 141-148. 10.3109\/08977199109000278.","journal-title":"Growth Factors"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1479-5876-11-81.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:00:23Z","timestamp":1630537223000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/1479-5876-11-81"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,27]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1464"],"URL":"https:\/\/doi.org\/10.1186\/1479-5876-11-81","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,27]]},"assertion":[{"value":"1 December 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"81"}}