Heparanase released from mesenchymal stem cells activates integrin beta1/HIF-2alpha/Flk-1 signaling and promotes endothelial cell migration and angiogenesis.

ABSTRACT: Heparanase plays important roles in tumor angiogenesis. Our previous study demonstrated that hypoxic preconditioning (HPC) enhanced the angiogenic and therapeutic effects of mesenchymal stem cells (MSCs), effects that were paralleled by enhanced heparanase expression. This study was designed to elucidate the role of heparanase in the improved therapeutic properties of HPC-MSCs and to explore underlying mechanisms using an ischemic rat hind limb model. MSCs transfected with heparanase (MSC(hpa) ) or empty vector (MSC(null) ) were delivered by intramuscular injections to ischemic hind limbs. Hind limbs that received MSC(hpa) recovered blood flow more rapidly at 7 days and acquired higher capillary density at 14 days compared with MSC(null) . Conditioned medium from MSC(hpa) increased endothe

SUBMITTER: Hu X 

PROVIDER: S-EPMC5108061 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature