VCAM-1(+) placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity
STEM CELL RESEARCH & THERAPY
Authors: Du, Wenjing; Li, Xue; Chi, Ying; Ma, Fengxia; Li, Zongjin; Yang, Shaoguang; Song, Baoquan; Cui, Junjie; Ma, Tao; Li, Juanjuan; Tian, Jianjian; Yang, Zhouxin; Feng, Xiaoming; Chen, Fang; Lu, Shihong; Liang, Lu; Han, Zhi-Bo; Han, Zhong-Chao
Introduction: Mesenchymal stem cells (MSCs) represent a heterogeneous cell population that is promising for regenerative medicine. The present study was designed to assess whether VCAM-1 can be used as a marker of MSC subpopulation with superior angiogenic potential. Methods: MSCs were isolated from placenta chorionic villi (CV). The VCAM-1(+/-) CV-MSCs population were separated by Flow Cytometry and subjected to a comparative analysis for their angiogenic properties including angiogenic genes expression, vasculo-angiogenic abilities on Matrigel in vitro and in vivo, angiogenic paracrine activities, cytokine array, and therapeutic angiogenesis in vascular ischemic diseases. Results: Angiogenic genes, including HGF, ANG, IL8, IL6, VEGF-A, TGF beta, MMP2 and bFGF, were up-regulated in VCAM-1(+)CV-MSCs. Consistently, angiogenic cytokines especially HGF, IL8, angiogenin, angiopoitin-2, mu PAR, CXCL1, IL-1 beta, IL-1 alpha, CSF2, CSF3, MCP-3, CTACK, and OPG were found to be significantly increased in VCAM-1(+) CV-MSCs. Moreover, VCAM-1(+)CV-MSCs showed remarkable vasculo-angiogenic abilities by angiogenesis analysis with Matrigel in vitro and in vivo and the conditioned medium of VCAM-1(+)CV-MSCs exerted markedly pro-proliferative and promigratory effects on endothelial cells compared to VCAM-1(-)CV-MSCs. Finally, transplantation of VCAM-1(+)CV-MSCs into the ischemic hind limb of BALB/c nude mice resulted in a significantly functional improvement in comparison with VCAM-1(-)CV-MSCs transplantation. Conclusions: VCAM-1(+)CV-MSCs possessed a favorable angiogenic paracrine activity and displayed therapeutic efficacy on hindlimb ischemia. Our results suggested that VCAM-1(+)CV-MSCs may represent an important subpopulation of MSC for efficient therapeutic angiogenesis.
TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects
Authors: Carlson, Christopher S.; Heagerty, Patrick J.; Nord, Alex S.; Pritchard, David K.; Ranchalis, Jane; Boguch, Joshua M.; Duan, Hangjun; Hatsukami, Thomas S.; Schwartz, Stephen M.; Rieder, Mark J.; Nickerson, Deborah A.; Jarvik, Gail P.
Inflammatory markers have consistently been associated with vascular disease. Evidence of genetic polymorphisms in inflammatory loci that predict severe carotid artery disease (CAAD) would suggest that this relationship is not secondary to other correlated factors, but related to inflammation itself. We examined the full common genetic variation in 42 inflammatory loci for prediction of severe CAAD versus ultrasound proven controls using a tagSNP approach. For selected loci, monocyte RNA levels were contrasted in subjects with and without CAAD. We confirm the association of IL6(-174), FGB (-455), and ALOX5 with CAAD and show that multiple ALOX5 SNPs independently predict CAAD. We provide evidence for previously unreported associations of SNPs in IL4R, NFKBIA, and PLG with CAAD, and weaker evidence for associations with CSF3, IL10RA, and VCAM1. The NFKBIA and IL10RA expression levels significantly differed between subjects with CAAD and controls. These results support a role for genetic variation related to inflammation in CAAD and a causal role for specific gene products.