Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419; Medical Innovation Technology Inc. (MEDINNO Inc.), The Reason Velley, Seoul 08517, Korea.
Medical Innovation Technology Inc. (MEDINNO Inc.), The Reason Velley, Seoul 08517; Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16149, Korea.
BMB Rep. 2022 Jul;55(7):336-341. doi: 10.5483/BMBRep.2022.55.7.003.
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. [BMB Reports 2022; 55(7): 336-341].
肢体供血动脉狭窄会引发严重的下肢缺血（CLI）。尽管 CLI 会导致不可逆转的后遗症，如截肢，但很少有治疗方法能诱导新的功能性血管形成。基于干细胞的促血管生成潜力，本研究旨在探讨牙髓干细胞（DPSCs）和人脐静脉内皮细胞（HUVECs）的联合应用是否能比单独应用 DPSCs 或 HUVECs 更有效地促进 CLI 中干细胞的治疗效果。与单独应用 DPSCs 或 HUVECs 相比，DPSCs+HUVECs 联合治疗可显著增加血流量，降低缺血损伤。DPSCs+HUVECs 组治疗效果的改善伴随着缺血组织中微血管数量的显著增加。体外增殖和管形成试验表明，DPSCs 条件培养基中的 VEGF 诱导了 HUVECs 的增殖和类似血管的管形成。总之，我们的研究结果表明，DPSCs 和 HUVECs 的联合应用通过 VEGF 介导的串扰对 CLI 具有显著更好的治疗效果。这种联合策略可用于开发 CLI 促血管生成再生治疗的新临床方案。[BMB 报告 2022; 55(7): 336-341]。
