Author:
Dao Mo,Tate Ciara C,McGrogan Michael,Case Casey C
Abstract
Abstract
Background
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 Notch1 intracellular domain (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.
Methods
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.
Results
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.
Conclusions
These data indicate that SB623 cell-secreted angiogenic factors promoted several aspects of angiogenesis, which likely contribute to promoting recovery in the injured brain.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference31 articles.
1. 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.
2. 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.
3. 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.
4. 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.
5. 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 ‘Off the shelf solution’ for critical limb ischemia?. J Transl Med. 2008, 6: 45-10.1186/1479-5876-6-45.
Cited by
31 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献