| First Author | Wagner NM | Year | 2013 |
| Journal | Int J Clin Exp Pathol | Volume | 6 |
| Issue | 12 | Pages | 2813-23 |
| PubMed ID | 24294367 | Mgi Jnum | J:325786 |
| Mgi Id | MGI:6871999 | Citation | Wagner NM, et al. (2013) TLR2-deficiency of cKit+ bone marrow cells is associated with augmented potency to stimulate angiogenic processes. Int J Clin Exp Pathol 6(12):2813-23 |
| abstractText | OBJECTIVE: Toll-like receptor 2 (TLR2)-deficiency is associated with the preservation of vascular function and TLR2-deficient (TLR2(-/-)) mice exhibit increased neovascularization following induction of hindlimb ischemia. Hematopoietic stem cells play an important role in ischemia-induced angiogenesis and we now investigated whether the effects observed in TLR2(-/-) mice may be attributed to TLR2 deficiency on bone marrow-derived stem cells. APPROACH AND RESULTS: cKit-positive (cKit(+)) bone marrow cells (BMC) were isolated from wild type (WT) and TLR2(-/-) mice employing MACS-bead technology. Co-incubation of TLR2(-/-)cKit(+) BMC with mature endothelial cells (ECs) resulted in increased tube formation of ECs on matrigel, augmented sprouting in a 3D-collagen matrix and increased migratory capacity compared to co-incubation with WT cKit(+) BMC. In an in vivo matrigel plug assay, TLR2(-/-)cKit(+) BMC exhibited enhanced formation of capillary-like networks. In a murine model of hindlimb ischemia, administration of TLR2(-/-) cKit(+) BMC to WT mice augmented capillary density and reperfusion of ischemic M. gastrocnemius muscle tissue to the level of TLR2(-/-) mice. Western Blot analysis revealed comparable expression of CXCR4 on TLR2(-/-)cKit(+) BMC but increased activation of the PI3K downstream signaling molecule protein kinase B (PKB/AKT) compared to WT cKit(+) cells. CONCLUSIONS: The absence of TLR2 on cKit(+) BMC is associated with augmented potency to support angiogenic processes in vitro and in vivo. Functional inhibition of TLR2 may therefore provide a novel tool to enhance stem cell function for the treatment of vascular diseases. |
