TLR2-deficiency of cKit+ bone marrow cells is associated with augmented potency to stimulate angiogenic processes

International Journal of Clinical and Experimental Pathology

Gabriele Noeldge-Schomburg¹  Antje Butschkau²¹  Laura Bierhansl¹  Nana-Maria Wagner¹  Jan Patrick Roesner¹  Brigitte Vollmar¹ 

关键词: TLR2;    cKit;    hematopoietic stem cells;    angiogenesis;    ischemia;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown