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Combinational stem cell therapy for critical hindlimb ischemia using dental pulp stem cells and human umbilical vein endothelial cells
Chung Kwon Kim 1,2,# (Research Professor), Ji-Yoon Hwang2,3,# (Research worker), Tae Hee Hong2 (Research worker), Du Man Lee2,4 (Research worker), Kyunghoon Lee1,3 (Professor), Hyun Nam3,5,6 (Research Professor), Kyeung Min Joo (Professor)
1Biomedical Institute for ConvergenceBiomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea,
2Medical Innovation Technology Inc. (MEDINNO Inc.), The Reason Velley, Seoul, 08517, Korea,
3Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16149, Korea,
4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea,
5Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea,
6Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16149, Republic of Korea
Abstract
Narrowed arteries to limbs provoke critical hindlimb ischemia (CLI). Although CLI results in irreversible sequelae, such as amputation, there are few therapeutic options that could induce formation of new functional blood vessels. Based on the proangiogenic potentials of stem cells, it was examined in this study whether combining dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) could potentiate therapeutic effects of stem cells for CLI compared with those of DPSCs or HUVECs alone. The combination therapy showed significantly higher blood flow and lower ischemia damage than did the other groups on CLI animal models. The improved therapeutic effects were accompanied by significantly more microvessels in the ischemic tissue than did the other groups. In vitro proliferation and tube formation assay showed that VEGF in the conditioned media of DPSCs induced proliferation and vessel-like tube formation of HUVECs. Altogether, our results demonstrated that the combination of DPSCs and HUVECs made significantly better therapeutic effects on CLI via VEGF-mediated crosstalk. This combinational strategy could be used to develop novel clinical protocols for proangiogenic regenerative treatments for CLI.
Keywords: Critical hindlimb ischemia, Combination, Dental pulp stem cells, Human umbilical vein endothelial cells, Angiogenesis
Abstract, Accepted Manuscript(in press) [Submitted on January 6, 2022, Accepted on February 11, 2022]
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