Combinatorial Treatment with Apelin-13 Enhances the Therapeutic Efficacy of a Preconditioned Cell-Based Therapy for Peripheral Ischemia

Scientific Reports
Makoto SamuraKimikazu Hamano

Abstract

Hypoxic pretreatment of peripheral blood mononuclear cells (PBMNCs) enhances therapeutic angiogenesis in ischemic tissues after cell transplantation. However, newly formed vessels generated using this approach are immature and insufficient for promoting functional recovery from severe ischemia. In this study, we examined whether apelin-13, a regulator of vessel maturation, could be an effective promoter of therapeutic angiogenesis, following severe limb ischemia. Combinatorial treatment of hypoxic preconditioned PBMNCs with apelin-13 resulted in increased blood perfusion and vascular reactivity in ischemic mouse hindlimbs compared with a monotherapy comprising each factor. Apelin-13 upregulated expression of PDGF-BB and TGF-β1 in hypoxic PBMNCs, as well as that of PDGFR-β in vascular smooth muscle cells (VSMCs). Proliferation and migration of VSMCs treated with apelin-13 was accelerated in the presence of PDGF-BB. Interestingly, expression of an apelin receptor, APJ, in PBMNC was increased under hypoxia but not under normoxia. In addition, an in vitro angiogenesis assay using a co-culture model comprising mouse thoracic aorta, hypoxic PBMNCs, and apelin-13 demonstrated that combinatorial treatment recruited mural cells to sprou...Continue Reading

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Citations

Feb 27, 2017·Journal of Translational Medicine·Makoto SamuraKimikazu Hamano
Dec 28, 2016·Clinica Chimica Acta; International Journal of Clinical Chemistry·Lele WuLanfang Li
Dec 4, 2016·Advanced Drug Delivery Reviews·Jayoung KimJordan J Green
Jun 18, 2020·International Journal of Molecular Sciences·Anne FrischRoland E Kälin
Feb 23, 2020·Advances in Medical Sciences·Javad MasoumiNajmeh Jamali
Mar 13, 2021·Scientific Reports·Judit BertaViktória László

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Methods Mentioned

BETA
femoral artery
density gradient centrifugation
PCR

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