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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Combination stem cell therapy using dental pulp stem cells and human umbilical vein endothelial cells for critical hindlimb ischemia

  • Kim, Chung Kwon (Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Hwang, Ji-Yoon (Medical Innovation Technology Inc. (MEDINNO Inc.)) ;
  • Hong, Tae Hee (Medical Innovation Technology Inc. (MEDINNO Inc.)) ;
  • Lee, Du Man (Medical Innovation Technology Inc. (MEDINNO Inc.)) ;
  • Lee, Kyunghoon (Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Nam, Hyun (Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Joo, Kyeung Min (Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University)
  • Received : 2022.01.06
  • Accepted : 2022.02.11
  • Published : 2022.07.31
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Abstract

Narrowing of arteries supplying blood to the limbs provokes critical hindlimb ischemia (CLI). Although CLI results in irreversible sequelae, such as amputation, few therapeutic options induce the formation of new functional blood vessels. Based on the proangiogenic potentials of stem cells, in this study, it was examined 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 CLI compared with those of DPSCs or HUVECs alone. The DPSCs+ HUVECs combination therapy resulted in significantly higher blood flow and lower ischemia damage than DPSCs or HUVECs alone. The improved therapeutic effects in the DPSCs+ HUVECs group were accompanied by a significantly higher number of microvessels in the ischemic tissue than in 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 had significantly better therapeutic effects on CLI via VEGF-mediated crosstalk. This combinational strategy could be used to develop novel clinical protocols for CLI proangiogenic regenerative treatments.

Keywords

Acknowledgement

This research was funded by the National Research Foundation (NRF-2016R1A5A2945889, NRF-2019R1I1A1A01059158, and NRF-2020R1F1A1073261) and Korea Basic Science Institute (2020R1A6C101A191).

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