Combination stem cell therapy using dental pulp stem cells and human umbilical vein endothelial cells for critical hindlimb ischemia
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Narrowing of arteries supplying blood to the limbs provokescritical hindlimb ischemia (CLI). Although CLI results in irreversiblesequelae, such as amputation, few therapeutic options inducethe formation of new functional blood vessels. Based onthe proangiogenic potentials of stem cells, in this study, it wasexamined whether a combination of dental pulp stem cells(DPSCs) and human umbilical vein endothelial cells (HUVECs)could result in enhanced therapeutic effects of stem cells for CLIcompared with those of DPSCs or HUVECs alone. The DPSCs+HUVECs combination therapy resulted in significantly higherblood flow and lower ischemia damage than DPSCs or HUVECsalone. The improved therapeutic effects in the DPSCs+ HUVECsgroup were accompanied by a significantly higher number ofmicrovessels in the ischemic tissue than in the other groups. Invitro proliferation and tube formation assay showed that VEGFin the conditioned media of DPSCs induced proliferation andvessel-like tube formation of HUVECs. Altogether, our resultsdemonstrated that the combination of DPSCs and HUVECs hadsignificantly better therapeutic effects on CLI via VEGF-mediatedcrosstalk. This combinational strategy could be used to developnovel clinical protocols for CLI proangiogenic regenerative treatments.
Abstract
Narrowing of arteries supplying blood to the limbs provokescritical hindlimb ischemia (CLI). Although CLI results in irreversiblesequelae, such as amputation, few therapeutic options inducethe formation of new functional blood vessels. Based onthe proangiogenic potentials of stem cells, in this study, it wasexamined whether a combination of dental pulp stem cells(DPSCs) and human umbilical vein endothelial cells (HUVECs)could result in enhanced therapeutic effects of stem cells for CLIcompared with those of DPSCs or HUVECs alone. The DPSCs+HUVECs combination therapy resulted in significantly higherblood flow and lower ischemia damage than DPSCs or HUVECsalone. The improved therapeutic effects in the DPSCs+ HUVECsgroup were accompanied by a significantly higher number ofmicrovessels in the ischemic tissue than in the other groups. Invitro proliferation and tube formation assay showed that VEGFin the conditioned media of DPSCs induced proliferation andvessel-like tube formation of HUVECs. Altogether, our resultsdemonstrated that the combination of DPSCs and HUVECs hadsignificantly better therapeutic effects on CLI via VEGF-mediatedcrosstalk. This combinational strategy could be used to developnovel clinical protocols for CLI proangiogenic regenerative treatments.
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